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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Helios expression coordinates the development of a subset of striatopallidal medium spiny neurons</title><author><name sortKey="Martin Iba Ez, Raquel" sort="Martin Iba Ez, Raquel" uniqKey="Martin Iba Ez R" first="Raquel" last="Martín-Ibá Ez">Raquel Martín-Ibá Ez</name><affiliation><nlm:aff id="af1"><addr-line>Stem Cells and Regenerative Medicine Laboratory</addr-line>,<institution>Production and Validation Center of Advanced Therapies (Creatio), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af2"><institution>Neuroscience Institute, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af3"><institution>August Pi i Sunyer Biomedical Research Institute (IDIBAPS)</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af4"><institution>Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED)</institution>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af5"><institution>Research and Development Unit, Production and Validation Center of Advanced Therapies (Creatio)</institution>,<addr-line>Faculty of Medicine and Health Sciences</addr-line>,<institution>University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Pardo, M Nica" sort="Pardo, M Nica" uniqKey="Pardo M" first="M Nica" last="Pardo">M Nica Pardo</name><affiliation><nlm:aff id="af1"><addr-line>Stem Cells and Regenerative Medicine Laboratory</addr-line>,<institution>Production and Validation Center of Advanced Therapies (Creatio), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af2"><institution>Neuroscience Institute, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af3"><institution>August Pi i Sunyer Biomedical Research Institute (IDIBAPS)</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af4"><institution>Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED)</institution>,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Giralt, Albert" sort="Giralt, Albert" uniqKey="Giralt A" first="Albert" last="Giralt">Albert Giralt</name><affiliation><nlm:aff id="af3"><institution>August Pi i Sunyer Biomedical Research Institute (IDIBAPS)</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af4"><institution>Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED)</institution>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af6"><addr-line>Pathophysiology of Neurodegenerative Diseases Laboratory</addr-line>,<institution>Production and Validation Center of Advanced Therapies (Creatio), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Miguez, Andres" sort="Miguez, Andres" uniqKey="Miguez A" first="Andrés" last="Miguez">Andrés Miguez</name><affiliation><nlm:aff id="af1"><addr-line>Stem Cells and Regenerative Medicine Laboratory</addr-line>,<institution>Production and Validation Center of Advanced Therapies (Creatio), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af2"><institution>Neuroscience Institute, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af3"><institution>August Pi i Sunyer Biomedical Research Institute (IDIBAPS)</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af4"><institution>Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED)</institution>,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Guardia, Ines" sort="Guardia, Ines" uniqKey="Guardia I" first="Inés" last="Guardia">Inés Guardia</name><affiliation><nlm:aff id="af1"><addr-line>Stem Cells and Regenerative Medicine Laboratory</addr-line>,<institution>Production and Validation Center of Advanced Therapies (Creatio), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af2"><institution>Neuroscience Institute, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af3"><institution>August Pi i Sunyer Biomedical Research Institute (IDIBAPS)</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af4"><institution>Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED)</institution>,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Marion Poll, Lucile" sort="Marion Poll, Lucile" uniqKey="Marion Poll L" first="Lucile" last="Marion-Poll">Lucile Marion-Poll</name><affiliation><nlm:aff id="af7"><institution>Inserm UMR-S839; Université Pierre et Marie Curie (UPMC, Paris 6), Sorbonne Universités; Institut du Fer à Moulin</institution>,<addr-line>75005 Paris</addr-line>,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Herranz, Cristina" sort="Herranz, Cristina" uniqKey="Herranz C" first="Cristina" last="Herranz">Cristina Herranz</name><affiliation><nlm:aff id="af1"><addr-line>Stem Cells and Regenerative Medicine Laboratory</addr-line>,<institution>Production and Validation Center of Advanced Therapies (Creatio), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af2"><institution>Neuroscience Institute, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af3"><institution>August Pi i Sunyer Biomedical Research Institute (IDIBAPS)</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af4"><institution>Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED)</institution>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af5"><institution>Research and Development Unit, Production and Validation Center of Advanced Therapies (Creatio)</institution>,<addr-line>Faculty of Medicine and Health Sciences</addr-line>,<institution>University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Esgleas, Miriam" sort="Esgleas, Miriam" uniqKey="Esgleas M" first="Miriam" last="Esgleas">Miriam Esgleas</name><affiliation><nlm:aff id="af1"><addr-line>Stem Cells and Regenerative Medicine Laboratory</addr-line>,<institution>Production and Validation Center of Advanced Therapies (Creatio), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af3"><institution>August Pi i Sunyer Biomedical Research Institute (IDIBAPS)</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af4"><institution>Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED)</institution>,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Garcia Diaz Barriga, Gerardo" sort="Garcia Diaz Barriga, Gerardo" uniqKey="Garcia Diaz Barriga G" first="Gerardo" last="Garcia-Díaz Barriga">Gerardo Garcia-Díaz Barriga</name><affiliation><nlm:aff id="af2"><institution>Neuroscience Institute, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af3"><institution>August Pi i Sunyer Biomedical Research Institute (IDIBAPS)</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af4"><institution>Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED)</institution>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af6"><addr-line>Pathophysiology of Neurodegenerative Diseases Laboratory</addr-line>,<institution>Production and Validation Center of Advanced Therapies (Creatio), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Edel, Michael J" sort="Edel, Michael J" uniqKey="Edel M" first="Michael J." last="Edel">Michael J. Edel</name><affiliation><nlm:aff id="af8"><addr-line>Control of Pluripotency Laboratory, Department of Biomedical Sciences, Faculty of Medicine and Health Science</addr-line>,<institution>University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af9"><institution>Victor Chang Cardiac Research Institute</institution>,<addr-line>Sydney, New South Wales</addr-line>,<country>2010 Australia</country></nlm:aff></affiliation><affiliation><nlm:aff id="af10"><institution>School of Medicine and Pharmacology, Anatomy, Physiology and Human Biology, CCTRM, University of Western Australia</institution>,<addr-line>Western Australia</addr-line>,<country>6009 Australia</country></nlm:aff></affiliation></author><author><name sortKey="Vicario Abej N, Carlos" sort="Vicario Abej N, Carlos" uniqKey="Vicario Abej N C" first="Carlos" last="Vicario-Abej N">Carlos Vicario-Abej N</name><affiliation><nlm:aff id="af4"><institution>Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED)</institution>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af11"><addr-line>Departamento de Neurobiología Molecular</addr-line>,<institution>Celular y del Desarrollo, Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC)</institution>,<addr-line>28002 Madrid</addr-line>,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Alberch, Jordi" sort="Alberch, Jordi" uniqKey="Alberch J" first="Jordi" last="Alberch">Jordi Alberch</name><affiliation><nlm:aff id="af2"><institution>Neuroscience Institute, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af3"><institution>August Pi i Sunyer Biomedical Research Institute (IDIBAPS)</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af4"><institution>Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED)</institution>,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Girault, Jean Antoine" sort="Girault, Jean Antoine" uniqKey="Girault J" first="Jean-Antoine" last="Girault">Jean-Antoine Girault</name><affiliation><nlm:aff id="af7"><institution>Inserm UMR-S839; Université Pierre et Marie Curie (UPMC, Paris 6), Sorbonne Universités; Institut du Fer à Moulin</institution>,<addr-line>75005 Paris</addr-line>,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Chan, Susan" sort="Chan, Susan" uniqKey="Chan S" first="Susan" last="Chan">Susan Chan</name><affiliation><nlm:aff id="af1"><addr-line>Stem Cells and Regenerative Medicine Laboratory</addr-line>,<institution>Production and Validation Center of Advanced Therapies (Creatio), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af2"><institution>Neuroscience Institute, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Kastner, Philippe" sort="Kastner, Philippe" uniqKey="Kastner P" first="Philippe" last="Kastner">Philippe Kastner</name><affiliation><nlm:aff id="af12"><addr-line>Department of Functional Genomics and Cancer</addr-line>,<institution>Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Inserm U964, Centre National de la Recherche Scientifique (CNRS) UMR 7104</institution>,<addr-line>67400 Illkirch-Graffenstaden</addr-line>,<country>France</country></nlm:aff></affiliation><affiliation><nlm:aff id="af13"><addr-line>Faculté de Médecine</addr-line>,<institution>Université de Strasbourg</institution>,<addr-line>67081 Strasbourg</addr-line>,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Canals, Josep M" sort="Canals, Josep M" uniqKey="Canals J" first="Josep M." last="Canals">Josep M. Canals</name><affiliation><nlm:aff id="af1"><addr-line>Stem Cells and Regenerative Medicine Laboratory</addr-line>,<institution>Production and Validation Center of Advanced Therapies (Creatio), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af2"><institution>Neuroscience Institute, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af3"><institution>August Pi i Sunyer Biomedical Research Institute (IDIBAPS)</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af4"><institution>Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED)</institution>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af5"><institution>Research and Development Unit, Production and Validation Center of Advanced Therapies (Creatio)</institution>,<addr-line>Faculty of Medicine and Health Sciences</addr-line>,<institution>University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">28289129</idno><idno type="pmc">5399659</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399659</idno><idno type="RBID">PMC:5399659</idno><idno type="doi">10.1242/dev.138248</idno><date when="2017">2017</date><idno type="wicri:Area/Pmc/Corpus">002401</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002401</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Helios expression coordinates the development of a subset of striatopallidal medium spiny neurons</title><author><name sortKey="Martin Iba Ez, Raquel" sort="Martin Iba Ez, Raquel" uniqKey="Martin Iba Ez R" first="Raquel" last="Martín-Ibá Ez">Raquel Martín-Ibá Ez</name><affiliation><nlm:aff id="af1"><addr-line>Stem Cells and Regenerative Medicine Laboratory</addr-line>,<institution>Production and Validation Center of Advanced Therapies (Creatio), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af2"><institution>Neuroscience Institute, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af3"><institution>August Pi i Sunyer Biomedical Research Institute (IDIBAPS)</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af4"><institution>Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED)</institution>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af5"><institution>Research and Development Unit, Production and Validation Center of Advanced Therapies (Creatio)</institution>,<addr-line>Faculty of Medicine and Health Sciences</addr-line>,<institution>University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Pardo, M Nica" sort="Pardo, M Nica" uniqKey="Pardo M" first="M Nica" last="Pardo">M Nica Pardo</name><affiliation><nlm:aff id="af1"><addr-line>Stem Cells and Regenerative Medicine Laboratory</addr-line>,<institution>Production and Validation Center of Advanced Therapies (Creatio), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af2"><institution>Neuroscience Institute, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af3"><institution>August Pi i Sunyer Biomedical Research Institute (IDIBAPS)</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af4"><institution>Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED)</institution>,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Giralt, Albert" sort="Giralt, Albert" uniqKey="Giralt A" first="Albert" last="Giralt">Albert Giralt</name><affiliation><nlm:aff id="af3"><institution>August Pi i Sunyer Biomedical Research Institute (IDIBAPS)</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af4"><institution>Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED)</institution>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af6"><addr-line>Pathophysiology of Neurodegenerative Diseases Laboratory</addr-line>,<institution>Production and Validation Center of Advanced Therapies (Creatio), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Miguez, Andres" sort="Miguez, Andres" uniqKey="Miguez A" first="Andrés" last="Miguez">Andrés Miguez</name><affiliation><nlm:aff id="af1"><addr-line>Stem Cells and Regenerative Medicine Laboratory</addr-line>,<institution>Production and Validation Center of Advanced Therapies (Creatio), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af2"><institution>Neuroscience Institute, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af3"><institution>August Pi i Sunyer Biomedical Research Institute (IDIBAPS)</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af4"><institution>Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED)</institution>,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Guardia, Ines" sort="Guardia, Ines" uniqKey="Guardia I" first="Inés" last="Guardia">Inés Guardia</name><affiliation><nlm:aff id="af1"><addr-line>Stem Cells and Regenerative Medicine Laboratory</addr-line>,<institution>Production and Validation Center of Advanced Therapies (Creatio), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af2"><institution>Neuroscience Institute, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af3"><institution>August Pi i Sunyer Biomedical Research Institute (IDIBAPS)</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af4"><institution>Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED)</institution>,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Marion Poll, Lucile" sort="Marion Poll, Lucile" uniqKey="Marion Poll L" first="Lucile" last="Marion-Poll">Lucile Marion-Poll</name><affiliation><nlm:aff id="af7"><institution>Inserm UMR-S839; Université Pierre et Marie Curie (UPMC, Paris 6), Sorbonne Universités; Institut du Fer à Moulin</institution>,<addr-line>75005 Paris</addr-line>,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Herranz, Cristina" sort="Herranz, Cristina" uniqKey="Herranz C" first="Cristina" last="Herranz">Cristina Herranz</name><affiliation><nlm:aff id="af1"><addr-line>Stem Cells and Regenerative Medicine Laboratory</addr-line>,<institution>Production and Validation Center of Advanced Therapies (Creatio), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af2"><institution>Neuroscience Institute, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af3"><institution>August Pi i Sunyer Biomedical Research Institute (IDIBAPS)</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af4"><institution>Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED)</institution>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af5"><institution>Research and Development Unit, Production and Validation Center of Advanced Therapies (Creatio)</institution>,<addr-line>Faculty of Medicine and Health Sciences</addr-line>,<institution>University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Esgleas, Miriam" sort="Esgleas, Miriam" uniqKey="Esgleas M" first="Miriam" last="Esgleas">Miriam Esgleas</name><affiliation><nlm:aff id="af1"><addr-line>Stem Cells and Regenerative Medicine Laboratory</addr-line>,<institution>Production and Validation Center of Advanced Therapies (Creatio), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af3"><institution>August Pi i Sunyer Biomedical Research Institute (IDIBAPS)</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af4"><institution>Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED)</institution>,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Garcia Diaz Barriga, Gerardo" sort="Garcia Diaz Barriga, Gerardo" uniqKey="Garcia Diaz Barriga G" first="Gerardo" last="Garcia-Díaz Barriga">Gerardo Garcia-Díaz Barriga</name><affiliation><nlm:aff id="af2"><institution>Neuroscience Institute, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af3"><institution>August Pi i Sunyer Biomedical Research Institute (IDIBAPS)</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af4"><institution>Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED)</institution>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af6"><addr-line>Pathophysiology of Neurodegenerative Diseases Laboratory</addr-line>,<institution>Production and Validation Center of Advanced Therapies (Creatio), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Edel, Michael J" sort="Edel, Michael J" uniqKey="Edel M" first="Michael J." last="Edel">Michael J. Edel</name><affiliation><nlm:aff id="af8"><addr-line>Control of Pluripotency Laboratory, Department of Biomedical Sciences, Faculty of Medicine and Health Science</addr-line>,<institution>University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af9"><institution>Victor Chang Cardiac Research Institute</institution>,<addr-line>Sydney, New South Wales</addr-line>,<country>2010 Australia</country></nlm:aff></affiliation><affiliation><nlm:aff id="af10"><institution>School of Medicine and Pharmacology, Anatomy, Physiology and Human Biology, CCTRM, University of Western Australia</institution>,<addr-line>Western Australia</addr-line>,<country>6009 Australia</country></nlm:aff></affiliation></author><author><name sortKey="Vicario Abej N, Carlos" sort="Vicario Abej N, Carlos" uniqKey="Vicario Abej N C" first="Carlos" last="Vicario-Abej N">Carlos Vicario-Abej N</name><affiliation><nlm:aff id="af4"><institution>Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED)</institution>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af11"><addr-line>Departamento de Neurobiología Molecular</addr-line>,<institution>Celular y del Desarrollo, Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC)</institution>,<addr-line>28002 Madrid</addr-line>,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Alberch, Jordi" sort="Alberch, Jordi" uniqKey="Alberch J" first="Jordi" last="Alberch">Jordi Alberch</name><affiliation><nlm:aff id="af2"><institution>Neuroscience Institute, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af3"><institution>August Pi i Sunyer Biomedical Research Institute (IDIBAPS)</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af4"><institution>Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED)</institution>,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Girault, Jean Antoine" sort="Girault, Jean Antoine" uniqKey="Girault J" first="Jean-Antoine" last="Girault">Jean-Antoine Girault</name><affiliation><nlm:aff id="af7"><institution>Inserm UMR-S839; Université Pierre et Marie Curie (UPMC, Paris 6), Sorbonne Universités; Institut du Fer à Moulin</institution>,<addr-line>75005 Paris</addr-line>,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Chan, Susan" sort="Chan, Susan" uniqKey="Chan S" first="Susan" last="Chan">Susan Chan</name><affiliation><nlm:aff id="af1"><addr-line>Stem Cells and Regenerative Medicine Laboratory</addr-line>,<institution>Production and Validation Center of Advanced Therapies (Creatio), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af2"><institution>Neuroscience Institute, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation></author><author><name sortKey="Kastner, Philippe" sort="Kastner, Philippe" uniqKey="Kastner P" first="Philippe" last="Kastner">Philippe Kastner</name><affiliation><nlm:aff id="af12"><addr-line>Department of Functional Genomics and Cancer</addr-line>,<institution>Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Inserm U964, Centre National de la Recherche Scientifique (CNRS) UMR 7104</institution>,<addr-line>67400 Illkirch-Graffenstaden</addr-line>,<country>France</country></nlm:aff></affiliation><affiliation><nlm:aff id="af13"><addr-line>Faculté de Médecine</addr-line>,<institution>Université de Strasbourg</institution>,<addr-line>67081 Strasbourg</addr-line>,<country>France</country></nlm:aff></affiliation></author><author><name sortKey="Canals, Josep M" sort="Canals, Josep M" uniqKey="Canals J" first="Josep M." last="Canals">Josep M. Canals</name><affiliation><nlm:aff id="af1"><addr-line>Stem Cells and Regenerative Medicine Laboratory</addr-line>,<institution>Production and Validation Center of Advanced Therapies (Creatio), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af2"><institution>Neuroscience Institute, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af3"><institution>August Pi i Sunyer Biomedical Research Institute (IDIBAPS)</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af4"><institution>Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED)</institution>,<country>Spain</country></nlm:aff></affiliation><affiliation><nlm:aff id="af5"><institution>Research and Development Unit, Production and Validation Center of Advanced Therapies (Creatio)</institution>,<addr-line>Faculty of Medicine and Health Sciences</addr-line>,<institution>University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></nlm:aff></affiliation></author></analytic><series><title level="j">Development (Cambridge, England)</title><idno type="ISSN">0950-1991</idno><idno type="eISSN">1477-9129</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Here, we unravel the mechanism of action of the Ikaros family zinc finger protein Helios (He) during the development of striatal medium spiny neurons (MSNs). He regulates the second wave of striatal neurogenesis involved in the generation of striatopallidal neurons, which express dopamine 2 receptor and enkephalin. To exert this effect, He is expressed in neural progenitor cells (NPCs) keeping them in the G<sub>1</sub>/G<sub>0</sub> phase of the cell cycle. Thus, a lack of He results in an increase of S-phase entry and S-phase length of NPCs, which in turn impairs striatal neurogenesis and produces an accumulation of the number of cycling NPCs in the germinal zone (GZ), which end up dying at postnatal stages. Therefore, <italic>He<sup>−/−</sup></italic> mice show a reduction in the number of dorso-medial striatal MSNs in the adult that produces deficits in motor skills acquisition. In addition, overexpression of <italic>He</italic> in NPCs induces misexpression of DARPP-32 when transplanted in mouse striatum. These findings demonstrate that He is involved in the correct development of a subset of striatopallidal MSNs and reveal new cellular mechanisms for neuronal development.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Agoston, D V" uniqKey="Agoston D">D. V. Agoston</name></author><author><name sortKey="Szemes, M" uniqKey="Szemes M">M. Szemes</name></author><author><name sortKey="Dobi, A" uniqKey="Dobi A">A. Dobi</name></author><author><name sortKey="Palkovits, M" uniqKey="Palkovits M">M. Palkovits</name></author><author><name sortKey="Georgopoulos, K" uniqKey="Georgopoulos K">K. Georgopoulos</name></author><author><name sortKey="Gyorgy, A" uniqKey="Gyorgy A">A. Gyorgy</name></author><author><name sortKey="Ring, M A" uniqKey="Ring M">M. A. Ring</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alsio, J M" uniqKey="Alsio J">J. M. Alsiö</name></author><author><name sortKey="Tarchini, B" uniqKey="Tarchini B">B. Tarchini</name></author><author><name sortKey="Cayouette, M" uniqKey="Cayouette M">M. Cayouette</name></author><author><name sortKey="Livesey, F J" uniqKey="Livesey F">F. J. Livesey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alvarez Buylla, A" uniqKey="Alvarez Buylla A">A. Alvarez-Buylla</name></author><author><name sortKey="Garcia Verdugo, J M" uniqKey="Garcia Verdugo J">J. M. García-Verdugo</name></author><author><name sortKey="Tramontin, A D" uniqKey="Tramontin A">A. D. Tramontin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arai, Y" uniqKey="Arai Y">Y. Arai</name></author><author><name sortKey="Pulvers, J N" uniqKey="Pulvers J">J. N. Pulvers</name></author><author><name sortKey="Haffner, C" uniqKey="Haffner C">C. Haffner</name></author><author><name sortKey="Schilling, B" uniqKey="Schilling B">B. Schilling</name></author><author><name sortKey="Nusslein, I" uniqKey="Nusslein I">I. Nüsslein</name></author><author><name sortKey="Calegari, F" uniqKey="Calegari F">F. Calegari</name></author><author><name sortKey="Huttner, W B" uniqKey="Huttner W">W. B. Huttner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arlotta, P" uniqKey="Arlotta P">P. Arlotta</name></author><author><name sortKey="Molyneaux, B J" uniqKey="Molyneaux B">B. J. Molyneaux</name></author><author><name sortKey="Jabaudon, D" uniqKey="Jabaudon D">D. Jabaudon</name></author><author><name sortKey="Yoshida, Y" uniqKey="Yoshida Y">Y. Yoshida</name></author><author><name sortKey="Macklis, J D" uniqKey="Macklis J">J. D. Macklis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bohner, A P" uniqKey="Bohner A">A. P. Bohner</name></author><author><name sortKey="Akers, R M" uniqKey="Akers R">R. M. Akers</name></author><author><name sortKey="Mcconnell, S K" uniqKey="Mcconnell S">S. K. McConnell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bosch, M" uniqKey="Bosch M">M. Bosch</name></author><author><name sortKey="Pineda, J R" uniqKey="Pineda J">J. R. Pineda</name></author><author><name sortKey="Su Ol, C" uniqKey="Su Ol C">C. Suñol</name></author><author><name sortKey="Petriz, J" uniqKey="Petriz J">J. Petriz</name></author><author><name sortKey="Cattaneo, E" uniqKey="Cattaneo E">E. Cattaneo</name></author><author><name sortKey="Alberch, J" uniqKey="Alberch J">J. Alberch</name></author><author><name sortKey="Canals, J M" uniqKey="Canals J">J. M. Canals</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brazel, C Y" uniqKey="Brazel C">C. Y. Brazel</name></author><author><name sortKey="Romanko, M J" uniqKey="Romanko M">M. J. Romanko</name></author><author><name sortKey="Rothstein, R P" uniqKey="Rothstein R">R. P. Rothstein</name></author><author><name sortKey="Levison, S W" uniqKey="Levison S">S. W. Levison</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Burek, M J" uniqKey="Burek M">M. J. Burek</name></author><author><name sortKey="Oppenheim, R W" uniqKey="Oppenheim R">R. W. Oppenheim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cai, Q" uniqKey="Cai Q">Q. Cai</name></author><author><name sortKey="Dierich, A" uniqKey="Dierich A">A. Dierich</name></author><author><name sortKey="Oulad Abdelghani, M" uniqKey="Oulad Abdelghani M">M. Oulad-Abdelghani</name></author><author><name sortKey="Chan, S" uniqKey="Chan S">S. Chan</name></author><author><name sortKey="Kastner, P" uniqKey="Kastner P">P. Kastner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Canals, J M" uniqKey="Canals J">J. M. Canals</name></author><author><name sortKey="Pineda, J R" uniqKey="Pineda J">J. R. Pineda</name></author><author><name sortKey="Torres Peraza, J F" uniqKey="Torres Peraza J">J. F. Torres-Peraza</name></author><author><name sortKey="Bosch, M" uniqKey="Bosch M">M. Bosch</name></author><author><name sortKey="Martin Iba Ez, R" uniqKey="Martin Iba Ez R">R. Martín-Ibañez</name></author><author><name sortKey="Mu Oz, M T" uniqKey="Mu Oz M">M. T. Muñoz</name></author><author><name sortKey="Mengod, G" uniqKey="Mengod G">G. Mengod</name></author><author><name sortKey="Ernfors, P" uniqKey="Ernfors P">P. Ernfors</name></author><author><name sortKey="Alberch, J" uniqKey="Alberch J">J. Alberch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cobb, B S" uniqKey="Cobb B">B. S. Cobb</name></author><author><name sortKey="Smale, S T" uniqKey="Smale S">S. T. Smale</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dimou, L" uniqKey="Dimou L">L. Dimou</name></author><author><name sortKey="Gotz, M" uniqKey="Gotz M">M. Götz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Durieux, P F" uniqKey="Durieux P">P. F. Durieux</name></author><author><name sortKey="Schiffmann, S N" uniqKey="Schiffmann S">S. N. Schiffmann</name></author><author><name sortKey="De Kerchove D Exaerde, A" uniqKey="De Kerchove D Exaerde A">A. de Kerchove d'Exaerde</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Edlund, T" uniqKey="Edlund T">T. Edlund</name></author><author><name sortKey="Jessell, T M" uniqKey="Jessell T">T. M. Jessell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ehrman, L A" uniqKey="Ehrman L">L. A. Ehrman</name></author><author><name sortKey="Mu, X" uniqKey="Mu X">X. Mu</name></author><author><name sortKey="Waclaw, R R" uniqKey="Waclaw R">R. R. Waclaw</name></author><author><name sortKey="Yoshida, Y" uniqKey="Yoshida Y">Y. Yoshida</name></author><author><name sortKey="Vorhees, C V" uniqKey="Vorhees C">C. V. Vorhees</name></author><author><name sortKey="Klein, W H" uniqKey="Klein W">W. H. Klein</name></author><author><name sortKey="Campbell, K" uniqKey="Campbell K">K. Campbell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Eisenstat, D D" uniqKey="Eisenstat D">D. D. Eisenstat</name></author><author><name sortKey="Liu, J K" uniqKey="Liu J">J. K. Liu</name></author><author><name sortKey="Mione, M" uniqKey="Mione M">M. Mione</name></author><author><name sortKey="Zhong, W" uniqKey="Zhong W">W. Zhong</name></author><author><name sortKey="Yu, G" uniqKey="Yu G">G. Yu</name></author><author><name sortKey="Anderson, S A" uniqKey="Anderson S">S. A. Anderson</name></author><author><name sortKey="Ghattas, I" uniqKey="Ghattas I">I. Ghattas</name></author><author><name sortKey="Puelles, L" uniqKey="Puelles L">L. Puelles</name></author><author><name sortKey="Rubenstein, J L" uniqKey="Rubenstein J">J. L. Rubenstein</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ericson, J" uniqKey="Ericson J">J. Ericson</name></author><author><name sortKey="Morton, S" uniqKey="Morton S">S. Morton</name></author><author><name sortKey="Kawakami, A" uniqKey="Kawakami A">A. Kawakami</name></author><author><name sortKey="Roelink, H" uniqKey="Roelink H">H. Roelink</name></author><author><name sortKey="Jessell, T M" uniqKey="Jessell T">T. M. Jessell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Flames, N" uniqKey="Flames N">N. Flames</name></author><author><name sortKey="Pla, R" uniqKey="Pla R">R. Pla</name></author><author><name sortKey="Gelman, D M" uniqKey="Gelman D">D. M. Gelman</name></author><author><name sortKey="Rubenstein, J L R" uniqKey="Rubenstein J">J. L. R. Rubenstein</name></author><author><name sortKey="Puelles, L" uniqKey="Puelles L">L. Puelles</name></author><author><name sortKey="Marin, O" uniqKey="Marin O">O. Marín</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Garcia Dominguez, M" uniqKey="Garcia Dominguez M">M. Garcia-Dominguez</name></author><author><name sortKey="Poquet, C" uniqKey="Poquet C">C. Poquet</name></author><author><name sortKey="Garel, S" uniqKey="Garel S">S. Garel</name></author><author><name sortKey="Charnay, P" uniqKey="Charnay P">P. Charnay</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Garel, S" uniqKey="Garel S">S. Garel</name></author><author><name sortKey="Marin, F" uniqKey="Marin F">F. Marín</name></author><author><name sortKey="Grosschedl, R" uniqKey="Grosschedl R">R. Grosschedl</name></author><author><name sortKey="Charnay, P" uniqKey="Charnay P">P. Charnay</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Georgopoulos, K" uniqKey="Georgopoulos K">K. Georgopoulos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gerfen, C R" uniqKey="Gerfen C">C. R. Gerfen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gong, S" uniqKey="Gong S">S. Gong</name></author><author><name sortKey="Zheng, C" uniqKey="Zheng C">C. Zheng</name></author><author><name sortKey="Doughty, M L" uniqKey="Doughty M">M. L. Doughty</name></author><author><name sortKey="Losos, K" uniqKey="Losos K">K. Losos</name></author><author><name sortKey="Didkovsky, N" uniqKey="Didkovsky N">N. Didkovsky</name></author><author><name sortKey="Schambra, U B" uniqKey="Schambra U">U. B. Schambra</name></author><author><name sortKey="Nowak, N J" uniqKey="Nowak N">N. J. Nowak</name></author><author><name sortKey="Joyner, A" uniqKey="Joyner A">A. Joyner</name></author><author><name sortKey="Leblanc, G" uniqKey="Leblanc G">G. Leblanc</name></author><author><name sortKey="Hatten, M E" uniqKey="Hatten M">M. E. Hatten</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gotz, M" uniqKey="Gotz M">M. Götz</name></author><author><name sortKey="Barde, Y A" uniqKey="Barde Y">Y.-A. Barde</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gould, E" uniqKey="Gould E">E. Gould</name></author><author><name sortKey="Reeves, A J" uniqKey="Reeves A">A. J. Reeves</name></author><author><name sortKey="Graziano, M S" uniqKey="Graziano M">M. S. Graziano</name></author><author><name sortKey="Gross, C G" uniqKey="Gross C">C. G. Gross</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Graybiel, A M" uniqKey="Graybiel A">A. M. Graybiel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hahm, K" uniqKey="Hahm K">K. Hahm</name></author><author><name sortKey="Cobb, B S" uniqKey="Cobb B">B. S. Cobb</name></author><author><name sortKey="Mccarty, A S" uniqKey="Mccarty A">A. S. McCarty</name></author><author><name sortKey="Brown, K E" uniqKey="Brown K">K. E. Brown</name></author><author><name sortKey="Klug, C A" uniqKey="Klug C">C. A. Klug</name></author><author><name sortKey="Lee, R" uniqKey="Lee R">R. Lee</name></author><author><name sortKey="Akashi, K" uniqKey="Akashi K">K. Akashi</name></author><author><name sortKey="Weissman, I L" uniqKey="Weissman I">I. L. Weissman</name></author><author><name sortKey="Fisher, A G" uniqKey="Fisher A">A. G. Fisher</name></author><author><name sortKey="Smale, S T" uniqKey="Smale S">S. T. Smale</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Harbour, J W" uniqKey="Harbour J">J. W. Harbour</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hardwick, L J A" uniqKey="Hardwick L">L. J. A. Hardwick</name></author><author><name sortKey="Philpott, A" uniqKey="Philpott A">A. Philpott</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="John, L B" uniqKey="John L">L. B. John</name></author><author><name sortKey="Yoong, S" uniqKey="Yoong S">S. Yoong</name></author><author><name sortKey="Ward, A C" uniqKey="Ward A">A. C. Ward</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jueptner, M" uniqKey="Jueptner M">M. Jueptner</name></author><author><name sortKey="Weiller, C" uniqKey="Weiller C">C. Weiller</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kanthan, R" uniqKey="Kanthan R">R. Kanthan</name></author><author><name sortKey="Fried, I" uniqKey="Fried I">I. Fried</name></author><author><name sortKey="Rueckl, T" uniqKey="Rueckl T">T. Rueckl</name></author><author><name sortKey="Senger, J L" uniqKey="Senger J">J.-L. Senger</name></author><author><name sortKey="Kanthan, S C" uniqKey="Kanthan S">S. C. Kanthan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, H J" uniqKey="Kim H">H.-J. Kim</name></author><author><name sortKey="Hida, H" uniqKey="Hida H">H. Hida</name></author><author><name sortKey="Jung, C G" uniqKey="Jung C">C.-G. Jung</name></author><author><name sortKey="Miura, Y" uniqKey="Miura Y">Y. Miura</name></author><author><name sortKey="Nishino, H" uniqKey="Nishino H">H. Nishino</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, H J" uniqKey="Kim H">H.-J. Kim</name></author><author><name sortKey="Barnitz, R A" uniqKey="Barnitz R">R. A. Barnitz</name></author><author><name sortKey="Kreslavsky, T" uniqKey="Kreslavsky T">T. Kreslavsky</name></author><author><name sortKey="Brown, F D" uniqKey="Brown F">F. D. Brown</name></author><author><name sortKey="Moffett, H" uniqKey="Moffett H">H. Moffett</name></author><author><name sortKey="Lemieux, M E" uniqKey="Lemieux M">M. E. Lemieux</name></author><author><name sortKey="Kaygusuz, Y" uniqKey="Kaygusuz Y">Y. Kaygusuz</name></author><author><name sortKey="Meissner, T" uniqKey="Meissner T">T. Meissner</name></author><author><name sortKey="Holderried, T A W" uniqKey="Holderried T">T. A. W. Holderried</name></author><author><name sortKey="Chan, S" uniqKey="Chan S">S. Chan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kreitzer, A C" uniqKey="Kreitzer A">A. C. Kreitzer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kristiansen, M" uniqKey="Kristiansen M">M. Kristiansen</name></author><author><name sortKey="Ham, J" uniqKey="Ham J">J. Ham</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lacomme, M" uniqKey="Lacomme M">M. Lacomme</name></author><author><name sortKey="Liaubet, L" uniqKey="Liaubet L">L. Liaubet</name></author><author><name sortKey="Pituello, F" uniqKey="Pituello F">F. Pituello</name></author><author><name sortKey="Bel Vialar, S" uniqKey="Bel Vialar S">S. Bel-Vialar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lange, C" uniqKey="Lange C">C. Lange</name></author><author><name sortKey="Huttner, W B" uniqKey="Huttner W">W. B. Huttner</name></author><author><name sortKey="Calegari, F" uniqKey="Calegari F">F. Calegari</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Leng, X" uniqKey="Leng X">X. Leng</name></author><author><name sortKey="Connell Crowley, L" uniqKey="Connell Crowley L">L. Connell-Crowley</name></author><author><name sortKey="Goodrich, D" uniqKey="Goodrich D">D. Goodrich</name></author><author><name sortKey="Harper, J W" uniqKey="Harper J">J. W. Harper</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lobo, M K" uniqKey="Lobo M">M. K. Lobo</name></author><author><name sortKey="Karsten, S L" uniqKey="Karsten S">S. L. Karsten</name></author><author><name sortKey="Gray, M" uniqKey="Gray M">M. Gray</name></author><author><name sortKey="Geschwind, D H" uniqKey="Geschwind D">D. H. Geschwind</name></author><author><name sortKey="Yang, X W" uniqKey="Yang X">X. W. Yang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lobo, M K" uniqKey="Lobo M">M. K. Lobo</name></author><author><name sortKey="Yeh, C" uniqKey="Yeh C">C. Yeh</name></author><author><name sortKey="Yang, X W" uniqKey="Yang X">X. W. Yang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lopez, F" uniqKey="Lopez F">F. Lopez</name></author><author><name sortKey="Belloc, F" uniqKey="Belloc F">F. Belloc</name></author><author><name sortKey="Lacombe, F" uniqKey="Lacombe F">F. Lacombe</name></author><author><name sortKey="Dumain, P" uniqKey="Dumain P">P. Dumain</name></author><author><name sortKey="Reiffers, J" uniqKey="Reiffers J">J. Reiffers</name></author><author><name sortKey="Bernard, P" uniqKey="Bernard P">P. Bernard</name></author><author><name sortKey="Boisseau, M R" uniqKey="Boisseau M">M. R. Boisseau</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lu, K M" uniqKey="Lu K">K.-M. Lu</name></author><author><name sortKey="Evans, S M" uniqKey="Evans S">S. M. Evans</name></author><author><name sortKey="Hirano, S" uniqKey="Hirano S">S. Hirano</name></author><author><name sortKey="Liu, F C" uniqKey="Liu F">F.-C. Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Luft, A R" uniqKey="Luft A">A. R. Luft</name></author><author><name sortKey="Buitrago, M M" uniqKey="Buitrago M">M. M. Buitrago</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lukas, J" uniqKey="Lukas J">J. Lukas</name></author><author><name sortKey="Herzinger, T" uniqKey="Herzinger T">T. Herzinger</name></author><author><name sortKey="Hansen, K" uniqKey="Hansen K">K. Hansen</name></author><author><name sortKey="Moroni, M C" uniqKey="Moroni M">M. C. Moroni</name></author><author><name sortKey="Resnitzky, D" uniqKey="Resnitzky D">D. Resnitzky</name></author><author><name sortKey="Helin, K" uniqKey="Helin K">K. Helin</name></author><author><name sortKey="Reed, S I" uniqKey="Reed S">S. I. Reed</name></author><author><name sortKey="Bartek, J" uniqKey="Bartek J">J. Bartek</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Martin Iba Ez, R" uniqKey="Martin Iba Ez R">R. Martín-Ibáñez</name></author><author><name sortKey="Crespo, E" uniqKey="Crespo E">E. Crespo</name></author><author><name sortKey="Urban, N" uniqKey="Urban N">N. Urbán</name></author><author><name sortKey="Sergent Tanguy, S" uniqKey="Sergent Tanguy S">S. Sergent-Tanguy</name></author><author><name sortKey="Herranz, C" uniqKey="Herranz C">C. Herranz</name></author><author><name sortKey="Jaumot, M" uniqKey="Jaumot M">M. Jaumot</name></author><author><name sortKey="Valiente, M" uniqKey="Valiente M">M. Valiente</name></author><author><name sortKey="Long, J E" uniqKey="Long J">J. E. Long</name></author><author><name sortKey="Pineda, J R" uniqKey="Pineda J">J. R. Pineda</name></author><author><name sortKey="Andreu, C" uniqKey="Andreu C">C. Andreu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Martin Iba Ez, R" uniqKey="Martin Iba Ez R">R. Martín-Ibáñez</name></author><author><name sortKey="Crespo, E" uniqKey="Crespo E">E. Crespo</name></author><author><name sortKey="Esgleas, M" uniqKey="Esgleas M">M. Esgleas</name></author><author><name sortKey="Urban, N" uniqKey="Urban N">N. Urban</name></author><author><name sortKey="Wang, B" uniqKey="Wang B">B. Wang</name></author><author><name sortKey="Waclaw, R" uniqKey="Waclaw R">R. Waclaw</name></author><author><name sortKey="Georgopoulos, K" uniqKey="Georgopoulos K">K. Georgopoulos</name></author><author><name sortKey="Martinez, S" uniqKey="Martinez S">S. Martínez</name></author><author><name sortKey="Campbell, K" uniqKey="Campbell K">K. Campbell</name></author><author><name sortKey="Vicario Abej N, C" uniqKey="Vicario Abej N C">C. Vicario-Abejón</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mason, H A" uniqKey="Mason H">H. A. Mason</name></author><author><name sortKey="Rakowiecki, S M" uniqKey="Rakowiecki S">S. M. Rakowiecki</name></author><author><name sortKey="Raftopoulou, M" uniqKey="Raftopoulou M">M. Raftopoulou</name></author><author><name sortKey="Nery, S" uniqKey="Nery S">S. Nery</name></author><author><name sortKey="Huang, Y" uniqKey="Huang Y">Y. Huang</name></author><author><name sortKey="Gridley, T" uniqKey="Gridley T">T. Gridley</name></author><author><name sortKey="Fishell, G" uniqKey="Fishell G">G. Fishell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcconnell, S K" uniqKey="Mcconnell S">S. K. McConnell</name></author><author><name sortKey="Kaznowski, C E" uniqKey="Kaznowski C">C. E. Kaznowski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Merkle, F T" uniqKey="Merkle F">F. T. Merkle</name></author><author><name sortKey="Alvarez Buylla, A" uniqKey="Alvarez Buylla A">A. Alvarez-Buylla</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Merot, Y" uniqKey="Merot Y">Y. Mérot</name></author><author><name sortKey="Retaux, S" uniqKey="Retaux S">S. Rétaux</name></author><author><name sortKey="Heng, J I T" uniqKey="Heng J">J. I.-T. Heng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Misumi, S" uniqKey="Misumi S">S. Misumi</name></author><author><name sortKey="Kim, T S" uniqKey="Kim T">T.-S. Kim</name></author><author><name sortKey="Jung, C G" uniqKey="Jung C">C.-G. Jung</name></author><author><name sortKey="Masuda, T" uniqKey="Masuda T">T. Masuda</name></author><author><name sortKey="Urakawa, S" uniqKey="Urakawa S">S. Urakawa</name></author><author><name sortKey="Isobe, Y" uniqKey="Isobe Y">Y. Isobe</name></author><author><name sortKey="Furuyama, F" uniqKey="Furuyama F">F. Furuyama</name></author><author><name sortKey="Nishino, H" uniqKey="Nishino H">H. Nishino</name></author><author><name sortKey="Hida, H" uniqKey="Hida H">H. Hida</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Miyachi, S" uniqKey="Miyachi S">S. Miyachi</name></author><author><name sortKey="Hikosaka, O" uniqKey="Hikosaka O">O. Hikosaka</name></author><author><name sortKey="Lu, X" uniqKey="Lu X">X. Lu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ninkovic, J" uniqKey="Ninkovic J">J. Ninkovic</name></author><author><name sortKey="Gotz, M" uniqKey="Gotz M">M. Götz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ohtani, K" uniqKey="Ohtani K">K. Ohtani</name></author><author><name sortKey="Degregori, J" uniqKey="Degregori J">J. DeGregori</name></author><author><name sortKey="Nevins, J R" uniqKey="Nevins J">J. R. Nevins</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ohtsubo, M" uniqKey="Ohtsubo M">M. Ohtsubo</name></author><author><name sortKey="Roberts, J M" uniqKey="Roberts J">J. M. Roberts</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ohtsubo, M" uniqKey="Ohtsubo M">M. Ohtsubo</name></author><author><name sortKey="Theodoras, A M" uniqKey="Theodoras A">A. M. Theodoras</name></author><author><name sortKey="Schumacher, J" uniqKey="Schumacher J">J. Schumacher</name></author><author><name sortKey="Roberts, J M" uniqKey="Roberts J">J. M. Roberts</name></author><author><name sortKey="Pagano, M" uniqKey="Pagano M">M. Pagano</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Okabe, M" uniqKey="Okabe M">M. Okabe</name></author><author><name sortKey="Ikawa, M" uniqKey="Ikawa M">M. Ikawa</name></author><author><name sortKey="Kominami, K" uniqKey="Kominami K">K. Kominami</name></author><author><name sortKey="Nakanishi, T" uniqKey="Nakanishi T">T. Nakanishi</name></author><author><name sortKey="Nishimune, Y" uniqKey="Nishimune Y">Y. Nishimune</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pilaz, L J" uniqKey="Pilaz L">L.-J. Pilaz</name></author><author><name sortKey="Patti, D" uniqKey="Patti D">D. Patti</name></author><author><name sortKey="Marcy, G" uniqKey="Marcy G">G. Marcy</name></author><author><name sortKey="Ollier, E" uniqKey="Ollier E">E. Ollier</name></author><author><name sortKey="Pfister, S" uniqKey="Pfister S">S. Pfister</name></author><author><name sortKey="Douglas, R J" uniqKey="Douglas R">R. J. Douglas</name></author><author><name sortKey="Betizeau, M" uniqKey="Betizeau M">M. Betizeau</name></author><author><name sortKey="Gautier, E" uniqKey="Gautier E">E. Gautier</name></author><author><name sortKey="Cortay, V" uniqKey="Cortay V">V. Cortay</name></author><author><name sortKey="Doerflinger, N" uniqKey="Doerflinger N">N. Doerflinger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pilz, G A" uniqKey="Pilz G">G.-A. Pilz</name></author><author><name sortKey="Shitamukai, A" uniqKey="Shitamukai A">A. Shitamukai</name></author><author><name sortKey="Reillo, I" uniqKey="Reillo I">I. Reillo</name></author><author><name sortKey="Pacary, E" uniqKey="Pacary E">E. Pacary</name></author><author><name sortKey="Schwausch, J" uniqKey="Schwausch J">J. Schwausch</name></author><author><name sortKey="Stahl, R" uniqKey="Stahl R">R. Stahl</name></author><author><name sortKey="Ninkovic, J" uniqKey="Ninkovic J">J. Ninkovic</name></author><author><name sortKey="Snippert, H J" uniqKey="Snippert H">H. J. Snippert</name></author><author><name sortKey="Clevers, H" uniqKey="Clevers H">H. Clevers</name></author><author><name sortKey="Godinho, L" uniqKey="Godinho L">L. Godinho</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rallu, M" uniqKey="Rallu M">M. Rallu</name></author><author><name sortKey="Corbin, J G" uniqKey="Corbin J">J. G. Corbin</name></author><author><name sortKey="Fishell, G" uniqKey="Fishell G">G. Fishell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rebollo, A" uniqKey="Rebollo A">A. Rebollo</name></author><author><name sortKey="Schmitt, C" uniqKey="Schmitt C">C. Schmitt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Resnitzky, D" uniqKey="Resnitzky D">D. Resnitzky</name></author><author><name sortKey="Gossen, M" uniqKey="Gossen M">M. Gossen</name></author><author><name sortKey="Bujard, H" uniqKey="Bujard H">H. Bujard</name></author><author><name sortKey="Reed, S I" uniqKey="Reed S">S. I. Reed</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sausbier, M" uniqKey="Sausbier M">M. Sausbier</name></author><author><name sortKey="Hu, H" uniqKey="Hu H">H. Hu</name></author><author><name sortKey="Arntz, C" uniqKey="Arntz C">C. Arntz</name></author><author><name sortKey="Feil, S" uniqKey="Feil S">S. Feil</name></author><author><name sortKey="Kamm, S" uniqKey="Kamm S">S. Kamm</name></author><author><name sortKey="Adelsberger, H" uniqKey="Adelsberger H">H. Adelsberger</name></author><author><name sortKey="Sausbier, U" uniqKey="Sausbier U">U. Sausbier</name></author><author><name sortKey="Sailer, C A" uniqKey="Sailer C">C. A. Sailer</name></author><author><name sortKey="Feil, R" uniqKey="Feil R">R. Feil</name></author><author><name sortKey="Hofmann, F" uniqKey="Hofmann F">F. Hofmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Scholzen, T" uniqKey="Scholzen T">T. Scholzen</name></author><author><name sortKey="Gerdes, J" uniqKey="Gerdes J">J. Gerdes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stroobants, S" uniqKey="Stroobants S">S. Stroobants</name></author><author><name sortKey="Gantois, I" uniqKey="Gantois I">I. Gantois</name></author><author><name sortKey="Pooters, T" uniqKey="Pooters T">T. Pooters</name></author><author><name sortKey="D Hooge, R" uniqKey="D Hooge R">R. D'Hooge</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Takahashi, T" uniqKey="Takahashi T">T. Takahashi</name></author><author><name sortKey="Nowakowski, R S" uniqKey="Nowakowski R">R. S. Nowakowski</name></author><author><name sortKey="Caviness, V S" uniqKey="Caviness V">V. S. Caviness</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Takahashi, T" uniqKey="Takahashi T">T. Takahashi</name></author><author><name sortKey="Nowakowski, R S" uniqKey="Nowakowski R">R. S. Nowakowski</name></author><author><name sortKey="Caviness, V S" uniqKey="Caviness V">V. S. Caviness</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tanabe, Y" uniqKey="Tanabe Y">Y. Tanabe</name></author><author><name sortKey="William, C" uniqKey="William C">C. William</name></author><author><name sortKey="Jessell, T M" uniqKey="Jessell T">T. M. Jessell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Turrero Garcia, M" uniqKey="Turrero Garcia M">M. Turrero García</name></author><author><name sortKey="Chang, Y" uniqKey="Chang Y">Y. Chang</name></author><author><name sortKey="Arai, Y" uniqKey="Arai Y">Y. Arai</name></author><author><name sortKey="Huttner, W B" uniqKey="Huttner W">W. B. Huttner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Urban, N" uniqKey="Urban N">N. Urbán</name></author><author><name sortKey="Martin Iba Ez, R" uniqKey="Martin Iba Ez R">R. Martín-Ibáñez</name></author><author><name sortKey="Herranz, C" uniqKey="Herranz C">C. Herranz</name></author><author><name sortKey="Esgleas, M" uniqKey="Esgleas M">M. Esgleas</name></author><author><name sortKey="Crespo, E" uniqKey="Crespo E">E. Crespo</name></author><author><name sortKey="Pardo, M" uniqKey="Pardo M">M. Pardo</name></author><author><name sortKey="Crespo Enriquez, I" uniqKey="Crespo Enriquez I">I. Crespo-Enríquez</name></author><author><name sortKey="Mendez G Mez, H R" uniqKey="Mendez G Mez H">H. R. Méndez-Gómez</name></author><author><name sortKey="Waclaw, R" uniqKey="Waclaw R">R. Waclaw</name></author><author><name sortKey="Chatzi, C" uniqKey="Chatzi C">C. Chatzi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vinueza Veloz, M F" uniqKey="Vinueza Veloz M">M. F. Vinueza Veloz</name></author><author><name sortKey="Buijsen, R A M" uniqKey="Buijsen R">R. A. M. Buijsen</name></author><author><name sortKey="Willemsen, R" uniqKey="Willemsen R">R. Willemsen</name></author><author><name sortKey="Cupido, A" uniqKey="Cupido A">A. Cupido</name></author><author><name sortKey="Bosman, L W J" uniqKey="Bosman L">L. W. J. Bosman</name></author><author><name sortKey="Koekkoek, S K E" uniqKey="Koekkoek S">S. K. E. Koekkoek</name></author><author><name sortKey="Potters, J W" uniqKey="Potters J">J. W. Potters</name></author><author><name sortKey="Oostra, B A" uniqKey="Oostra B">B. A. Oostra</name></author><author><name sortKey="De Zeeuw, C I" uniqKey="De Zeeuw C">C. I. De Zeeuw</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Voorn, P" uniqKey="Voorn P">P. Voorn</name></author><author><name sortKey="Vanderschuren, L J M J" uniqKey="Vanderschuren L">L. J. M. J. Vanderschuren</name></author><author><name sortKey="Groenewegen, H J" uniqKey="Groenewegen H">H. J. Groenewegen</name></author><author><name sortKey="Robbins, T W" uniqKey="Robbins T">T. W. Robbins</name></author><author><name sortKey="Pennartz, C M A" uniqKey="Pennartz C">C. M. A. Pennartz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Waclaw, R R" uniqKey="Waclaw R">R. R. Waclaw</name></author><author><name sortKey="Wang, B" uniqKey="Wang B">B. Wang</name></author><author><name sortKey="Pei, Z" uniqKey="Pei Z">Z. Pei</name></author><author><name sortKey="Ehrman, L A" uniqKey="Ehrman L">L. A. Ehrman</name></author><author><name sortKey="Campbell, K" uniqKey="Campbell K">K. Campbell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yin, H H" uniqKey="Yin H">H. H. Yin</name></author><author><name sortKey="Knowlton, B J" uniqKey="Knowlton B">B. J. Knowlton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yin, H H" uniqKey="Yin H">H. H. Yin</name></author><author><name sortKey="Knowlton, B J" uniqKey="Knowlton B">B. J. Knowlton</name></author><author><name sortKey="Balleine, B W" uniqKey="Balleine B">B. W. Balleine</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yoshida, T" uniqKey="Yoshida T">T. Yoshida</name></author><author><name sortKey="Georgopoulos, K" uniqKey="Georgopoulos K">K. Georgopoulos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yun, K" uniqKey="Yun K">K. Yun</name></author><author><name sortKey="Fischman, S" uniqKey="Fischman S">S. Fischman</name></author><author><name sortKey="Johnson, J" uniqKey="Johnson J">J. Johnson</name></author><author><name sortKey="Hrabe De Angelis, M" uniqKey="Hrabe De Angelis M">M. Hrabe de Angelis</name></author><author><name sortKey="Weinmaster, G" uniqKey="Weinmaster G">G. Weinmaster</name></author><author><name sortKey="Rubenstein, J L R" uniqKey="Rubenstein J">J. L. R. Rubenstein</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, Z" uniqKey="Zhang Z">Z. Zhang</name></author><author><name sortKey="Swindle, C S" uniqKey="Swindle C">C. S. Swindle</name></author><author><name sortKey="Bates, J T" uniqKey="Bates J">J. T. Bates</name></author><author><name sortKey="Ko, R" uniqKey="Ko R">R. Ko</name></author><author><name sortKey="Cotta, C V" uniqKey="Cotta C">C. V. Cotta</name></author><author><name sortKey="Klug, C A" uniqKey="Klug C">C. A. Klug</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Development</journal-id><journal-id journal-id-type="iso-abbrev">Development</journal-id><journal-id journal-id-type="publisher-id">DEV</journal-id><journal-id journal-id-type="hwp">develop</journal-id><journal-title-group><journal-title>Development (Cambridge, England)</journal-title></journal-title-group><issn pub-type="ppub">0950-1991</issn><issn pub-type="epub">1477-9129</issn><publisher><publisher-name>The Company of Biologists Ltd</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">28289129</article-id><article-id pub-id-type="pmc">5399659</article-id><article-id pub-id-type="doi">10.1242/dev.138248</article-id><article-id pub-id-type="publisher-id">DEV138248</article-id><article-categories><subj-group subj-group-type="hwp-journal-coll"><subject>205</subject></subj-group><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>Helios expression coordinates the development of a subset of striatopallidal medium spiny neurons</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Martín-Ibáñez</surname><given-names>Raquel</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="aff" rid="af2">2</xref><xref ref-type="aff" rid="af3">3</xref><xref ref-type="aff" rid="af4">4</xref><xref ref-type="aff" rid="af5">5</xref><xref ref-type="author-notes" rid="AN1">**</xref></contrib><contrib contrib-type="author"><name><surname>Pardo</surname><given-names>Mónica</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="aff" rid="af2">2</xref><xref ref-type="aff" rid="af3">3</xref><xref ref-type="aff" rid="af4">4</xref><xref ref-type="author-notes" rid="AN1">**</xref><xref ref-type="author-notes" rid="AN2">*</xref></contrib><contrib contrib-type="author"><name><surname>Giralt</surname><given-names>Albert</given-names></name><xref ref-type="aff" rid="af3">3</xref><xref ref-type="aff" rid="af4">4</xref><xref ref-type="aff" rid="af6">6</xref><xref ref-type="author-notes" rid="AN3">‡</xref></contrib><contrib contrib-type="author"><name><surname>Miguez</surname><given-names>Andrés</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="aff" rid="af2">2</xref><xref ref-type="aff" rid="af3">3</xref><xref ref-type="aff" rid="af4">4</xref></contrib><contrib contrib-type="author"><name><surname>Guardia</surname><given-names>Inés</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="aff" rid="af2">2</xref><xref ref-type="aff" rid="af3">3</xref><xref ref-type="aff" rid="af4">4</xref></contrib><contrib contrib-type="author"><name><surname>Marion-Poll</surname><given-names>Lucile</given-names></name><xref ref-type="aff" rid="af7">7</xref><xref ref-type="author-notes" rid="AN4">§</xref></contrib><contrib contrib-type="author"><name><surname>Herranz</surname><given-names>Cristina</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="aff" rid="af2">2</xref><xref ref-type="aff" rid="af3">3</xref><xref ref-type="aff" rid="af4">4</xref><xref ref-type="aff" rid="af5">5</xref></contrib><contrib contrib-type="author"><name><surname>Esgleas</surname><given-names>Miriam</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="aff" rid="af3">3</xref><xref ref-type="aff" rid="af4">4</xref><xref ref-type="author-notes" rid="AN5">¶</xref></contrib><contrib contrib-type="author"><name><surname>Garcia-Díaz Barriga</surname><given-names>Gerardo</given-names></name><xref ref-type="aff" rid="af2">2</xref><xref ref-type="aff" rid="af3">3</xref><xref ref-type="aff" rid="af4">4</xref><xref ref-type="aff" rid="af6">6</xref></contrib><contrib contrib-type="author"><name><surname>Edel</surname><given-names>Michael J.</given-names></name><xref ref-type="aff" rid="af8">8</xref><xref ref-type="aff" rid="af9">9</xref><xref ref-type="aff" rid="af10">10</xref></contrib><contrib contrib-type="author"><name><surname>Vicario-Abejón</surname><given-names>Carlos</given-names></name><xref ref-type="aff" rid="af4">4</xref><xref ref-type="aff" rid="af11">11</xref></contrib><contrib contrib-type="author"><name><surname>Alberch</surname><given-names>Jordi</given-names></name><xref ref-type="aff" rid="af2">2</xref><xref ref-type="aff" rid="af3">3</xref><xref ref-type="aff" rid="af4">4</xref><xref ref-type="author-notes" rid="AN2">*</xref></contrib><contrib contrib-type="author"><name><surname>Girault</surname><given-names>Jean-Antoine</given-names></name><xref ref-type="aff" rid="af7">7</xref></contrib><contrib contrib-type="author"><name><surname>Chan</surname><given-names>Susan</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><name><surname>Kastner</surname><given-names>Philippe</given-names></name><xref ref-type="aff" rid="af12">12</xref><xref ref-type="aff" rid="af13">13</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="false">http://orcid.org/0000-0001-6829-7670</contrib-id><name><surname>Canals</surname><given-names>Josep M.</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="aff" rid="af2">2</xref><xref ref-type="aff" rid="af3">3</xref><xref ref-type="aff" rid="af4">4</xref><xref ref-type="aff" rid="af5">5</xref><xref ref-type="corresp" rid="cor1">‡‡</xref></contrib></contrib-group><aff id="af1"><label>1</label><addr-line>Stem Cells and Regenerative Medicine Laboratory</addr-line>,<institution>Production and Validation Center of Advanced Therapies (Creatio), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></aff><aff id="af2"><label>2</label><institution>Neuroscience Institute, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></aff><aff id="af3"><label>3</label><institution>August Pi i Sunyer Biomedical Research Institute (IDIBAPS)</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></aff><aff id="af4"><label>4</label><institution>Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED)</institution>,<country>Spain</country></aff><aff id="af5"><label>5</label><institution>Research and Development Unit, Production and Validation Center of Advanced Therapies (Creatio)</institution>,<addr-line>Faculty of Medicine and Health Sciences</addr-line>,<institution>University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></aff><aff id="af6"><label>6</label><addr-line>Pathophysiology of Neurodegenerative Diseases Laboratory</addr-line>,<institution>Production and Validation Center of Advanced Therapies (Creatio), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></aff><aff id="af7"><label>7</label><institution>Inserm UMR-S839; Université Pierre et Marie Curie (UPMC, Paris 6), Sorbonne Universités; Institut du Fer à Moulin</institution>,<addr-line>75005 Paris</addr-line>,<country>France</country></aff><aff id="af8"><label>8</label><addr-line>Control of Pluripotency Laboratory, Department of Biomedical Sciences, Faculty of Medicine and Health Science</addr-line>,<institution>University of Barcelona</institution>,<addr-line>08036 Barcelona</addr-line>,<country>Spain</country></aff><aff id="af9"><label>9</label><institution>Victor Chang Cardiac Research Institute</institution>,<addr-line>Sydney, New South Wales</addr-line>,<country>2010 Australia</country></aff><aff id="af10"><label>10</label><institution>School of Medicine and Pharmacology, Anatomy, Physiology and Human Biology, CCTRM, University of Western Australia</institution>,<addr-line>Western Australia</addr-line>,<country>6009 Australia</country></aff><aff id="af11"><label>11</label><addr-line>Departamento de Neurobiología Molecular</addr-line>,<institution>Celular y del Desarrollo, Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC)</institution>,<addr-line>28002 Madrid</addr-line>,<country>Spain</country></aff><aff id="af12"><label>12</label><addr-line>Department of Functional Genomics and Cancer</addr-line>,<institution>Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Inserm U964, Centre National de la Recherche Scientifique (CNRS) UMR 7104</institution>,<addr-line>67400 Illkirch-Graffenstaden</addr-line>,<country>France</country></aff><aff id="af13"><label>13</label><addr-line>Faculté de Médecine</addr-line>,<institution>Université de Strasbourg</institution>,<addr-line>67081 Strasbourg</addr-line>,<country>France</country></aff><author-notes><fn id="AN2" fn-type="present-address"><label>*</label><p>Present address: Developmental Neurobiology and Regeneration Group, Department of Cell Biology, University of Barcelona, Barcelona, Spain.</p></fn><fn id="AN3" fn-type="present-address"><label>‡</label><p>Present address: Inserm UMR-S839; Université Pierre et Marie Curie (UPMC, Paris 6), Sorbonne Universités; Institut du Fer à Moulin, Paris, France.</p></fn><fn id="AN4" fn-type="present-address"><label>§</label><p>Present address: Institut Curie, PSL Research University, CNRS UMR3215, Inserm U934, Mammalian Developmental Epigenetics group, Paris, France.</p></fn><fn id="AN5" fn-type="present-address"><label>¶</label><p>Present address: Institute of Stem Cell Research, Helmholtz Center Munich, Munich, Germany.</p></fn><fn id="AN1" fn-type="equal"><label>**</label><p>These authors contributed equally to this work</p></fn><corresp id="cor1"><label>‡‡</label>Author for correspondence (<email>jmcanals@ub.edu</email>)</corresp></author-notes><pub-date pub-type="ppub"><day>15</day><month>4</month><year>2017</year></pub-date><pub-date pub-type="pmc-release"><day>15</day><month>4</month><year>2017</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>144</volume><issue>8</issue><fpage>1566</fpage><lpage>1577</lpage><history><date date-type="received"><day>5</day><month>4</month><year>2016</year></date><date date-type="accepted"><day>3</day><month>3</month><year>2017</year></date></history><permissions><copyright-statement>© 2017. Published by The Company of Biologists Ltd</copyright-statement><copyright-year>2017</copyright-year><license license-type="open-access"><ali:license_ref specific-use="vor">http://creativecommons.org/licenses/by/3.0</ali:license_ref><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<uri xlink:href="http://creativecommons.org/licenses/by/3.0">http://creativecommons.org/licenses/by/3.0</uri>), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.</license-p></license></permissions><self-uri content-type="pdf" xlink:href="develop-144-138248.pdf"></self-uri><abstract><p>Here, we unravel the mechanism of action of the Ikaros family zinc finger protein Helios (He) during the development of striatal medium spiny neurons (MSNs). He regulates the second wave of striatal neurogenesis involved in the generation of striatopallidal neurons, which express dopamine 2 receptor and enkephalin. To exert this effect, He is expressed in neural progenitor cells (NPCs) keeping them in the G<sub>1</sub>/G<sub>0</sub> phase of the cell cycle. Thus, a lack of He results in an increase of S-phase entry and S-phase length of NPCs, which in turn impairs striatal neurogenesis and produces an accumulation of the number of cycling NPCs in the germinal zone (GZ), which end up dying at postnatal stages. Therefore, <italic>He<sup>−/−</sup></italic> mice show a reduction in the number of dorso-medial striatal MSNs in the adult that produces deficits in motor skills acquisition. In addition, overexpression of <italic>He</italic> in NPCs induces misexpression of DARPP-32 when transplanted in mouse striatum. These findings demonstrate that He is involved in the correct development of a subset of striatopallidal MSNs and reveal new cellular mechanisms for neuronal development.</p></abstract><abstract abstract-type="precis"><p><bold>Summary:</bold> The transcription factor Helios regulates G1-S transition to promote neuronal differentiation of a striatopallidal neuronal subpopulation involved in motor skill acquisition.</p></abstract><kwd-group><title>KEY WORDS</title><kwd>Ikaros</kwd><kwd>Neurogenesis</kwd><kwd>Medium spiny neurons</kwd><kwd>Cell cycle</kwd><kwd>Cell death</kwd><kwd>Ikzf2</kwd></kwd-group><funding-group specific-use="FundRef"><award-group><funding-source><institution-wrap><institution>Ministerio de Economía y Competitividad</institution><institution-id>http://dx.doi.org/10.13039/501100003329</institution-id></institution-wrap></funding-source><award-id>BFU2010-19630</award-id><award-id>SAF 2014-57160-R</award-id><award-id>SAF2015-66505-R</award-id></award-group></funding-group><funding-group specific-use="FundRef"><award-group><funding-source><institution-wrap><institution>Instituto de Salud Carlos III</institution><institution-id>http://dx.doi.org/10.13039/501100004587</institution-id></institution-wrap></funding-source></award-group></funding-group><funding-group specific-use="FundRef"><award-group><funding-source><institution-wrap><institution>European Regional Development Fund</institution><institution-id>http://dx.doi.org/10.13039/501100008530</institution-id></institution-wrap></funding-source></award-group></funding-group><funding-group specific-use="FundRef"><award-group><funding-source><institution-wrap><institution>Generalitat de Catalunya</institution><institution-id>http://dx.doi.org/10.13039/501100002809</institution-id></institution-wrap></funding-source><award-id>2014SGR-968</award-id></award-group></funding-group><funding-group specific-use="FundRef"><award-group><funding-source><institution-wrap><institution>Fundació la Marató de TV3</institution><institution-id>http://dx.doi.org/10.13039/100008666</institution-id></institution-wrap></funding-source><award-id>20140130/1</award-id></award-group></funding-group><funding-group specific-use="FundRef"><award-group><funding-source><institution-wrap><institution>CHDI Foundation</institution><institution-id>http://dx.doi.org/10.13039/100005725</institution-id></institution-wrap></funding-source><award-id>A-7332</award-id></award-group></funding-group></article-meta></front><body><sec sec-type="intro" id="s1"><title>INTRODUCTION</title><p>The mammalian striatum controls body movements through a sophisticated neuronal network that is dependent on the neurogenesis of two major classes of striatal neurons: the striatal projection neurons (or medium spiny neurons; MSNs) and the interneurons. MSNs are subdivided into two subpopulations: neurons that constitute the direct (or striatonigral) pathway and preferentially express substance P (SP) and D1R (dopamine receptor 1; DRD1), and neurons of the indirect (or striatopallidal) pathway, which mainly express enkephalin (ENK) and D2R (dopamine receptor 2; DRD2) (<xref rid="DEV138248C23" ref-type="bibr">Gerfen, 1992</xref>). These two populations are differentially distributed within the striatal compartments. Striatal patches or striosomes mainly contain SP<sup>+</sup> MSNs, but both MSN subpopulations, SP<sup>+</sup> and ENK<sup>+</sup>, are located in the matrix (<xref rid="DEV138248C23" ref-type="bibr">Gerfen, 1992</xref>).</p><p>During embryonic development, radial glial cells (RGCs) from the ventricle wall of the lateral ganglionic eminence (LGE) undergo successive divisions to expand the pool of neural progenitor cells (NPCs), thereby increasing the volume of the germinal zone (subventricular zone; SVZ) (for reviews, see <xref rid="DEV138248C25" ref-type="bibr">Götz and Barde, 2005</xref>; <xref rid="DEV138248C51" ref-type="bibr">Merkle and Alvarez-Buylla, 2006</xref>). At certain developmental stages, NPCs differentiate into immature neurons that migrate radially to the mantle zone (MZ) (<xref rid="DEV138248C25" ref-type="bibr">Götz and Barde, 2005</xref>; <xref rid="DEV138248C51" ref-type="bibr">Merkle and Alvarez-Buylla, 2006</xref>; <xref rid="DEV138248C52" ref-type="bibr">Mérot et al., 2009</xref>). Two waves of striatal neurogenesis segregate MSNs into two principal compartments: the patches, generated during the first neurogenic wave [starting at embryonic day (E) 12.5 in mouse]; and the matrix, developed during late striatal neurogenesis (starting at E14.5 in mouse) (<xref rid="DEV138248C23" ref-type="bibr">Gerfen, 1992</xref>; <xref rid="DEV138248C49" ref-type="bibr">Mason et al., 2005</xref>).</p><p>Within the LGE, transcription factors such as Gsx1 and Gsx2 (formerly named Gsh1 and Gsh2), Ascl1 (formerly named Mash1) and members of the Dlx family display specific patterns of expression within the GZ and the MZ, and they have been implicated in LGE patterning and/or differentiation (<xref rid="DEV138248C17" ref-type="bibr">Eisenstat et al., 1999</xref>; <xref rid="DEV138248C62" ref-type="bibr">Rallu et al., 2002</xref>; <xref rid="DEV138248C75" ref-type="bibr">Waclaw et al., 2009</xref>; <xref rid="DEV138248C79" ref-type="bibr">Yun et al., 2002</xref>). In addition, the transcription factors Ebf1, Isl1, Ctip2 (also known as Bcl11b), and Ikaros family members are mainly expressed in the MZ of the LGE where they regulate terminal differentiation of striatal projection neurons (<xref rid="DEV138248C5" ref-type="bibr">Arlotta et al., 2008</xref>; <xref rid="DEV138248C16" ref-type="bibr">Ehrman et al., 2013</xref>; <xref rid="DEV138248C20" ref-type="bibr">Garcia-Dominguez et al., 2003</xref>; <xref rid="DEV138248C21" ref-type="bibr">Garel et al., 1999</xref>; <xref rid="DEV138248C41" ref-type="bibr">Lobo et al., 2006</xref>, <xref rid="DEV138248C42" ref-type="bibr">2008</xref>; <xref rid="DEV138248C47" ref-type="bibr">Martín-Ibáñez et al., 2010</xref>).</p><p>Ikaros family members are transcription factors that play essential roles during lymphocyte development (<xref rid="DEV138248C12" ref-type="bibr">Cobb and Smale, 2005</xref>; <xref rid="DEV138248C22" ref-type="bibr">Georgopoulos, 2002</xref>; <xref rid="DEV138248C78" ref-type="bibr">Yoshida and Georgopoulos, 2014</xref>). Ikaros is the founder member of this family of DNA-binding proteins, which consists of Ikaros, Helios (He), Aiolos, Eos and Pegasus (Ikzf1-5, respectively – Mouse Genome Informatics) (<xref rid="DEV138248C31" ref-type="bibr">John et al., 2009</xref>; <xref rid="DEV138248C63" ref-type="bibr">Rebollo and Schmitt, 2003</xref>; <xref rid="DEV138248C78" ref-type="bibr">Yoshida and Georgopoulos, 2014</xref>). In addition, Ikaros has been implicated in CNS development (<xref rid="DEV138248C1" ref-type="bibr">Agoston et al., 2007</xref>; <xref rid="DEV138248C2" ref-type="bibr">Alsiö et al., 2013</xref>; <xref rid="DEV138248C47" ref-type="bibr">Martín-Ibáñez et al., 2010</xref>). We have recently described that He is also implicated in striatal development (<xref rid="DEV138248C48" ref-type="bibr">Martín-Ibáñez et al., 2012</xref>). Within the LGE, <italic>He</italic> is expressed from E14.5 to postnatal day (P) 15 in both the GZ and the MZ, and its expression is downstream of <italic>Gsx2</italic> and <italic>Dlx1/2</italic> (<xref rid="DEV138248C48" ref-type="bibr">Martín-Ibáñez et al., 2012</xref>). However, little is known about mechanisms of action of He during this developmental process.</p><p>Here, we demonstrate that <italic>He</italic> is expressed by NPCs at the G<sub>0</sub>/G<sub>1</sub>-phase of the cell cycle and induces neuronal differentiation by decreasing the levels of cyclin E and blocking the progression of these NPCs into S phase. Consequently, in the absence of <italic>He</italic>, proliferating NPCs accumulate in the GZ and the number of <italic>Ctip2</italic><sup>+</sup> and DARPP-32 (PPP1R1B)<sup>+</sup> MSNs is reduced in the striatum resulting in disturbance of motor skill learning.</p></sec><sec sec-type="results" id="s2"><title>RESULTS</title><sec id="s2a"><title><italic>He</italic> loss induces aberrant striatal neurogenesis accompanied by de-regulation of NPC proliferation</title><p>Here, we demonstrated that He is expressed from E12.5 in scattered cells (<uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S1</uri>) until P15 peaking at E18.5 (<xref rid="DEV138248C48" ref-type="bibr">Martín-Ibáñez et al., 2012</xref>). He showed preferential expression in D2R-eGFP neurons (mean±s.e.m.: 46.69±8.37% of He<sup>+</sup> cells co-labeled with D2R; <xref ref-type="fig" rid="DEV138248F1">Fig. 1</xref>A; <uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S2B</uri>) and <italic>Penk</italic> (preproenkephalin)<sup>+</sup> MSNs (89.05±5.77% of He<sup>+</sup> cells co-labeled with <italic>Penk</italic>; <uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S3</uri>). In contrast, few D1R-eGFP<sup>+</sup> neurons and <italic>Tac1</italic> (tachykinin A, also known as tachykinin 1)<sup>+</sup> neurons co-expressed He (3.94±2.53% and 18.20±2.1% of He<sup>+</sup> cells co-labeled with D1R and <italic>Tac1</italic>, respectively; <xref ref-type="fig" rid="DEV138248F1">Fig. 1</xref>A; <uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S2A; Fig. S3B,C</uri>). We next examined striatal birth-dating in <italic>He</italic> knockout (<italic>He</italic><sup>−/−</sup>) and wild-type (wt) mice at different embryonic developmental stages (<xref ref-type="fig" rid="DEV138248F1">Fig. 1</xref>B-E). The first wave of striatal birthdating at E12.5 was not altered, as no differences were found in the total number of bromodeoxyuridine (BrdU)<sup>+</sup> cells between <italic>He</italic><sup>−/−</sup> and wt mice (<xref ref-type="fig" rid="DEV138248F1">Fig. 1</xref>C). However, lack of <italic>He</italic> induced a significant reduction in the second wave of striatal birthdating at E14.5 (<xref ref-type="fig" rid="DEV138248F1">Fig. 1</xref>D). No significant differences were found between genotypes at E16.5 (<xref ref-type="fig" rid="DEV138248F1">Fig. 1</xref>E). This striatal birthdating impairment disturbed MSN generation as the density and total number of Ctip2-positive cells was decreased in <italic>He</italic><sup>−/−</sup> mice compared with wt mice at E18.5 (<xref ref-type="fig" rid="DEV138248F1">Fig. 1</xref>F,G), suggesting a defect in the second neurogenic wave. In agreement, we observed that He<sup>+</sup> cells were mainly generated during the second wave of striatal neurogenesis (<uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S4</uri>), between E14.5 (<uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Figs. S4E-G</uri>) and E16.5 (<uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Figs. S4H-J</uri>). Only a few cells were observed to be born at earlier stages (E13.5; <uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Figs. S4B-D</uri>).
<fig id="DEV138248F1" orientation="portrait" position="float"><label>Fig. 1.</label><caption><p><bold><italic>He</italic> is necessary for the second wave of striatal neurogenesis.</bold> (A) Double immunohistochemistry against He and GFP in the D1R-eGFP mice and in the D2R-eGFP mice (images show DLS and VLS, respectively). Unfilled arrowheads show single-labeled cells and filled arrowheads show double-positive cells. Scale bars: 15 μm. (B) Schematic timeline of birthdating experiments performed in <italic>He</italic><sup>−/−</sup> or wt mice. (C) No differences in neurogenesis were detected at E12.5 between <italic>He</italic><sup>−/−</sup> and wt mice. (D) <italic>He</italic><sup>−/−</sup> mice exhibited lower levels of neurogenesis than wt mice at E14.5. (E) No differences in neurogenesis were detected at E16.5 between <italic>He</italic><sup>−/−</sup> and wt mice. (F) Representative images of Ctip2<sup>+</sup> neurons in the E18.5 (mid-striatal primordium is shown). Scale bar: 120 µm. (G) Quantification of the density and total number of Ctip2<italic><sup>+</sup></italic> cells in the whole striatal primordium reveals a significant reduction in <italic>He</italic><sup>−/−</sup> mice compare with wt mice. Results represent the mean±s.e.m. of 4-5 mice per condition. Statistical analysis was performed using Student's <italic>t</italic>-test; *<italic>P</italic><0.05, **<italic>P</italic><0.005.</p></caption><graphic xlink:href="develop-144-138248-g1"></graphic></fig></p><p>To assess whether He was expressed by proliferative cells in the LGE, we performed double staining for He and Ki67 (Mki67) at E16.5, BrdU or phospho-histone H3 (PH3) at E14.5. Our results showed that He<sup>+</sup> and Ki67<sup>+</sup> areas were mainly coincident at the GZ-MZ border at E16.5 (<xref ref-type="fig" rid="DEV138248F2">Fig. 2</xref>A). Within this area, He was expressed by NPCs expressing a low level of Ki67 (<xref ref-type="fig" rid="DEV138248F2">Fig. 2</xref>B,C) but not by cells expressing a high level of Ki67<sup>+</sup> (<xref ref-type="fig" rid="DEV138248F2">Fig. 2</xref>D; see <uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S5</uri> for quantification details). However, there was a lack of colocalization between He and short-pulsed BrdU NPCs (<xref ref-type="fig" rid="DEV138248F2">Fig. 2</xref>E,F), and He and PH3<sup>+</sup> NPCs (<xref ref-type="fig" rid="DEV138248F2">Fig. 2</xref>G,H). Interestingly, He only colocalized with Ki67-expressing cells during the neurogenic period as we could not observe colocalization from E18.5 onwards (<uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S6</uri>).
<fig id="DEV138248F2" orientation="portrait" position="float"><label>Fig. 2.</label><caption><p><bold>He</bold><bold>is expressed in NPCs at G<sub>1</sub> cell cycle phase and regulates their proliferation.</bold> (A) E16.5 striatal primordium, double stained against Ki67 and He. He<sup>+</sup> and Ki67<sup>+</sup> cells are coincident at the GZ-MZ border. Scale bar: 200 µm. (B) High magnification image of Ki67-He double immunohistochemistry at the dorsal striatal primordium shows that some cells are double positive at the GZ-MZ border. Filled arrows indicate double-positive cells and unfilled arrows point to Ki67 single-labeled cells. Scale bar: 50 µm. (C,D) At the GZ-MZ border, cells expressing a low level of Ki67 (Ki<italic><sup>low</sup></italic>) express He (C), whereas cells expressing a high level of Ki67 (Ki<italic><sup>high</sup></italic>) do not express He (D). Scale bars: 20 µm. (E,F) Double staining for BrdU and He shows that cells in S phase are not positive for He at E14.5 in the dorsomedial LGE. (E) High magnification picture shows that although He<sup>+</sup> and BrdU<sup>+</sup> cells are located in the same area, they do not colocalize. (F) Unfilled arrowheads indicate BrdU<sup>+</sup> cells that have recently entered S phase as shown by the appearance of transcription units; filled arrowheads indicate cells that incorporated BrdU at more advanced cell cycle stages. Scale bars: 50 µm. (G,H) There is no coincidence between He-expressing cells and cells in M phase as detected by PH3 staining; low (G) and high (H) magnification images of DMS are shown. Scale bars: 50 µm. (I-L) Quantification of the total number of proliferating cells in the whole GZ show that lack of <italic>He</italic> induces a significant increase at E14.5 (I), E16.5 (J) and P3 (K) and a significant decrease at P7 (L) compared with wt mice. Results represent the mean±s.e.m. of 5-7 mice per condition. Statistical analysis was performed using Student's <italic>t</italic>-test; *<italic>P</italic><0.05, ***<italic>P</italic><0.001.</p></caption><graphic xlink:href="develop-144-138248-g2"></graphic></fig></p><p>Analysis of the number of cycling cells at different developmental stages in <italic>He</italic><sup>−/−</sup> and wt mice (<xref ref-type="fig" rid="DEV138248F2">Fig. 2</xref>I-L) showed that the total number of proliferating cells in the GZ was significantly increased from E14.5 to P3 (<xref ref-type="fig" rid="DEV138248F2">Fig. 2</xref>I-K), inducing an enlargement of the proliferative area stained with Ki67 (<uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S7</uri>). Interestingly, this feature reverted at P7, when the number of proliferating cells in <italic>He</italic><sup>−/−</sup> mice decreased with respect to wt mice (<xref ref-type="fig" rid="DEV138248F2">Fig. 2</xref>L; <uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S8</uri>). To analyze whether a specific subpopulation of progenitors was more compromised than others, we counted the percentage of PH3<sup>+</sup> basal, subapical and apical progenitors as described by <xref rid="DEV138248C61" ref-type="bibr">Pilz et al. (2013)</xref> (<uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S9A,B</uri>). No differences were found between <italic>He<sup>−/−</sup></italic> and wt mice (<uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S9B</uri>). We also analyzed by QPCR the expression of striatal progenitor markers at E16.5. No differences were found in the levels of mRNA for these markers in <italic>He<sup>−/−</sup></italic> compared with wt mice (<uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S9C</uri>).</p><p>To elucidate further the role of He in NPC proliferation, we performed loss-of-function (LOF) and gain-of-function (GOF) <italic>in vitro</italic> studies using a neurosphere assay (<uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S10</uri>). There was an increase in the number of proliferating cells in the absence of <italic>He</italic> (<uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S10A,C,E,F</uri>). Accordingly, <italic>He</italic> overexpression significantly reduced the number of proliferating NPCs with respect to the control eGFP overexpressing NPCs (<uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S10B,D</uri>). In addition, in the absence of <italic>He</italic>, NPCs were less prone to differentiate to β-III-tubulin<sup>+</sup> neurons (<uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S10H</uri>). In contrast, an increase in the number of neurons was observed after <italic>He</italic> overexpression (<uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S10I-K</uri>). Interestingly, <italic>He</italic> did not exert any change in the percentage of GFAP<sup>+</sup> cells in the LOF or in the GOF experiments (<uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S10H,I</uri>). Consequently, <italic>He<sup>−/−</sup></italic> mice did not present any defects in astrocyte differentiation compared with wt mice (<uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S11A-D</uri>). In fact, we did not observe colocalization between He and GFAP (<uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S11E</uri>).</p></sec><sec id="s2b"><title>He controls proliferation through regulation of the G<sub>1</sub>-S checkpoint</title><p>To understand the cellular mechanism by which He regulates NPC proliferation and neurogenesis, we next analyzed the cell cycle. We observed that lack of <italic>He</italic> induced a significant increase in NPC S-phase length that, in turn, increased cell cycle length as measured by an accumulative exposure to BrdU (see Materials and Methods; <xref rid="DEV138248C39" ref-type="bibr">Lange et al., 2009</xref>) (<xref ref-type="fig" rid="DEV138248F3">Fig. 3</xref>A,C). However, no differences were observed between the length of the G<sub>2</sub>/M phases in NPCs derived from <italic>He</italic><sup>−/−</sup> compared with wt mice, as determined by analysis of the mitotic BrdU labeling index as described previously (<xref rid="DEV138248C69" ref-type="bibr">Takahashi et al., 1995</xref>) (<xref ref-type="fig" rid="DEV138248F3">Fig. 3</xref>B,C; <uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S12</uri>). Representation of the percentage of cell cycle phases respect to the total cell cycle length clearly demonstrated an elongation of S-phase length when <italic>He</italic> was knocked down (<xref ref-type="fig" rid="DEV138248F3">Fig. 3</xref>C). Consistently, <italic>He</italic> overexpression induced a severe reduction of S-phase length (GOF; <xref ref-type="fig" rid="DEV138248F3">Fig. 3</xref>D). Our results also showed that in the absence of <italic>He</italic> more NPCs entered S phase (punctate BrdU<sup>+</sup>/EdU<sup>+</sup>; <xref ref-type="fig" rid="DEV138248F3">Fig. 3</xref>E-H) but the number of cells exiting S phase was not altered (BrdU<sup>+</sup>/EdU<sup>−</sup>; see ‘S-phase analysis’ in Materials and Methods; <xref rid="DEV138248C39" ref-type="bibr">Lange et al., 2009</xref>) (<xref ref-type="fig" rid="DEV138248F3">Fig. 3</xref>E,F). In addition, no differences were found in the number of cells exiting the cell cycle (BrdU<sup>+</sup>/Ki67<sup>−</sup>; see ‘Cell cycle index’ in Materials and Methods; <xref rid="DEV138248C72" ref-type="bibr">Urbán et al., 2010</xref>) in LOF (<uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S13A,B,D</uri>) or GOF (<uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S13C</uri>) experiments.
<fig id="DEV138248F3" orientation="portrait" position="float"><label>Fig. 3.</label><caption><p><bold><italic>He</italic> is necessary for cell cycle S-phase regulation.</bold> (A) <italic>He</italic><sup>−/−</sup> mice-derived neurospheres exhibited an increase in the length of S phase and cell cycle compared with wt mice-derived neurospheres. (B) Mitotic BrdU labeling index, which is used to calculate G<sub>2</sub>/M phase length, was the same in both wt and <italic>He<sup>−/−</sup></italic> mice-derived neurospheres. (C,D) Schematic of the percentages of the length of the cell cycle phases with respect to the total cell cycle duration obtained from LOF (C) and GOF (D) experiments. (E) Schematic timeline of S-phase entry/exit experiments performed with a double pulse of BrdU and EdU in wt and <italic>He</italic><sup>−/−</sup> mice-derived neurospheres. (F) A higher number of NPCs entered S phase in <italic>He</italic><sup>−/−</sup> mice-derived neurospheres compared with wt mice-derived ones, whereas no differences were observed between both cultures in the number of cells that exit S phase. (G,H) Representative images of BrdU and EdU double staining performed in wt and <italic>He</italic><sup>−/−</sup> mice-derived neurospheres. Arrows indicate double-positive cells. Scale bar: 50 µm. Results represent the mean±s.e.m. of 4-5 LGE-derived neurosphere cultures. Statistical analysis was performed using Student's <italic>t</italic>-test; *<italic>P</italic><0.05, **<italic>P</italic><0.005.</p></caption><graphic xlink:href="develop-144-138248-g3"></graphic></fig></p><p>In order to demonstrate the mechanism by which He controls S-phase entry, we next analyzed the protein levels of cyclin E (<xref ref-type="fig" rid="DEV138248F4">Fig. 4</xref>), a key regulator of the transition from G<sub>1</sub> to S phase (<xref rid="DEV138248C58" ref-type="bibr">Ohtsubo et al., 1995</xref>). NPCs derived from <italic>He<sup>−/−</sup></italic> mice presented increased levels of PCNA, a marker of cell proliferation, and cyclin E (<xref ref-type="fig" rid="DEV138248F4">Fig. 4</xref>A-D). Accordingly, <italic>He</italic> overexpression (<xref ref-type="fig" rid="DEV138248F4">Fig. 4</xref>E-H) produced a reduction of PCNA and cyclin E protein levels (<xref ref-type="fig" rid="DEV138248F4">Fig. 4</xref>E-H), and a drastic reduction of cyclin E mRNA levels (<xref ref-type="fig" rid="DEV138248F4">Fig. 4</xref>J). Similarly, <italic>in vivo</italic> analysis showed that an increased number of NPCs had entered into S phase in the GZ of <italic>He<sup>−/−</sup></italic> compared with wt mice (<xref ref-type="fig" rid="DEV138248F4">Fig. 4</xref>K), which was accompanied by increased protein levels of cyclin E in the LGE (<xref ref-type="fig" rid="DEV138248F4">Fig. 4</xref>L,M). Chromatin immunoprecipitation experiments performed by Kim and co-workers (<xref rid="DEV138248C35" ref-type="bibr">Kim et al., 2015</xref>) demonstrated that He binds the cyclin E gene (<italic>Ccne1</italic>) promoter site and another site downstream of the gene (<xref ref-type="fig" rid="DEV138248F4">Fig. 4</xref>N). However, no changes of the two cyclin E regulators E2F1 and retinoblastoma (Rb; Rb1) (<xref rid="DEV138248C29" ref-type="bibr">Harbour, 2000</xref>; <xref rid="DEV138248C56" ref-type="bibr">Ohtani et al., 1995</xref>) were observed in NPCs derived from <italic>He<sup>−/−</sup></italic> mice (<uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S14</uri>). Altogether, these results suggest that He might control cell cycle progression through regulation of cyclin E expression.
<fig id="DEV138248F4" orientation="portrait" position="float"><label>Fig. 4.</label><caption><p><bold>He regulates cyclin E expression.</bold> (A-D) PCNA (A,C) and cyclin E (Cy.E; B,D) protein quantification show a significant increase in the levels of both proteins in <italic>He<sup>−/−</sup></italic>-derived neurospheres compared with wt neurospheres. Representative blots are shown for PCNA (C) and cyclin E (D). (E-H) By contrast, <italic>He</italic> overexpression induces a significant decrease in PCNA (E,G) and cyclin E (F,H) protein levels compared with the control eGFP. Representative blots are shown for PCNA (G) and cyclin E (H). (I) mRNA expression of <italic>He</italic> in neurosphere cultures overexpressing <italic>He</italic> or the control eGFP. (J) Cyclin E mRNA levels are downregulated in <italic>He</italic> overexpressing neurospheres compared with the control eGFP. (K) <italic>In vivo</italic> analysis shows an increased percentage of cells entering into S phase in <italic>He<sup>−/−</sup></italic> LGEs compared with wt at E14.5. (L,M) Quantification of <italic>He<sup>−/−</sup></italic> and wt E14.5 LGEs indicates significantly increased protein expression of cyclin E in the absence of <italic>He</italic>. (M) Representative blots are shown for cyclin E in LOF <italic>in vivo</italic> experiments. (N) Cumulative counts peak graph from the chip-Seq analysis of <italic>He</italic> interaction. The cyclin E (<italic>Ccne1</italic>) gene region shows two prominent hits one within the proximal promoter region, and one downstream of the gene. Tubulin (Tub) was used as loading control for western blots. For <italic>in vitro</italic> studies, results represent the mean±s.e.m. of 4-5 LGE-derived neurosphere cultures. RT-PCR results represent the mean±s.e.m. of 4-5 independent samples and are expressed relative to control eGFP, considered as 100%. For <italic>in vivo</italic> studies, results represent the mean±s.e.m. of 4-5 LGEs. Statistical analysis was performed using Student's <italic>t</italic>-test; *<italic>P</italic><0.05, **<italic>P</italic><0.005.</p></caption><graphic xlink:href="develop-144-138248-g4"></graphic></fig></p></sec><sec id="s2c"><title>Postnatal cell death is increased in <italic>He<sup>−/−</sup></italic> mice</title><p>We next investigated whether cell death was altered in the absence of <italic>He</italic> during embryonic and postnatal stages. Cleaved caspase-3 immunohistochemistry did not reveal any differences between <italic>He</italic><sup>−/−</sup> and wt mice at embryonic stages (E14.5, E16.5 and E18.5; data not shown). However, a significant increase in the number of apoptotic cells was detected in the GZ and the MZ at P3 in <italic>He</italic><sup>−/−</sup> mice (<xref ref-type="fig" rid="DEV138248F5">Fig. 5</xref>A-D), which normalizes at P7 (<xref ref-type="fig" rid="DEV138248F5">Fig. 5</xref>E,F). To check whether cell death is related to a delay in the differentiation of NPCs, we applied an ethynyl deoxyuridine (EdU) pulse at E18.5 and double staining for EdU and cleaved caspase-3 (<xref ref-type="fig" rid="DEV138248F5">Fig. 5</xref>G) or neural markers (<uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S15</uri>) at P3. EdU<sup>+</sup> apoptotic cells were found in the MZ of <italic>He</italic><sup>−/−</sup> mice (<xref ref-type="fig" rid="DEV138248F5">Fig. 5</xref>H-K) and they were positive for the neuronal marker NeuN (Rbfox3) (71.3±7.10% of cleaved caspase-3<sup>+</sup> cells co-labeled with NeuN; <uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S15</uri>). These results suggest that in the absence of <italic>He</italic> there is a delayed differentiation of NPCs, which subsequently die.
<fig id="DEV138248F5" orientation="portrait" position="float"><label>Fig. 5.</label><caption><p><bold><italic>He</italic> knockout mice</bold><bold>exhibit</bold><bold>increased programmed cell death at postnatal stages.</bold> (A,B) Representative photomicrographs corresponding to P3 striatal coronal sections from wt (A) and <italic>He</italic><sup>−/−</sup> (B) mice immunostained for cleaved caspase 3. Scale bars: 200 µm. Ctx, cortex. (C) Lack of <italic>He</italic> induces a significant increase in the total number of cleaved caspase-3 (C-Casp3)<sup>+</sup> cells in the GZ at P3. (D) <italic>He</italic><sup>−/−</sup> mice exhibited an increase in the total number of C-Casp3<sup>+</sup> cells in the MZ at P3 compared with wt mice. (E,F) No differences in the total number of C-Casp3<sup>+</sup> cells were observed between genotypes in the GZ (E) or in the MZ at P7 (F). (G) Injection of EdU at E18.5 and recovery of the <italic>He</italic><sup>−/−</sup> pups at P3 permitted the examination of whether cells that exit the cell cycle after E18.5 and migrate to the striatum MZ are positive for C-Casp3. (H-K) Representative photomicrographs of striatal coronal ventral section showing colocalization of EdU and C-Casp3. Scale bar: 30 µm. Results represent the mean±s.e.m. of 4-5 mice per condition. Statistical analysis was performed using Student's <italic>t</italic>-test; *<italic>P</italic><0.05, **<italic>P</italic><0.005.</p></caption><graphic xlink:href="develop-144-138248-g5"></graphic></fig></p></sec><sec id="s2d"><title><italic>He</italic> is necessary for MSN development</title><p>We next characterized the striatum of <italic>He</italic><sup>−/−</sup> adult mice. First, we studied brain hemisphere volume and detected a slight decrease in <italic>He</italic><sup>−/−</sup> mice compared with wt mice (<uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S16A,C</uri>; 8.36% decrease). Interestingly, characterization of striatal volume revealed a larger and significant reduction in <italic>He</italic><sup>−/−</sup> compared with wt mice (<uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S16B,C</uri>; 20.17% decrease). The ratio of striatal versus hemisphere volume showed that striatal volume is selectively disturbed in <italic>He</italic><sup>−/−</sup> mice (wt, 18.23±0.79%; <italic>He</italic><sup>−/−</sup>, 15.45±0.60%), showing a 15.24% reduction of relative striatal volume. Stereological analysis of calbindin<sup>+</sup> and DARPP-32<sup>+</sup> neurons revealed a significant decrease in the density (<uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S16D,E,H,I</uri>) and total number of MSNs in the striatum of <italic>He</italic><sup>−/−</sup> compared with wt mice (<xref ref-type="fig" rid="DEV138248F6">Fig. 6</xref>A,B). We also analyzed the density of DARPP-32<sup>+</sup> neurons in different striatal areas including the dorso-medial striatum (DMS), dorso-lateral striatum (DLS), ventro-medial striatum (VMS) and ventro-lateral striatum (VLS) (<xref ref-type="fig" rid="DEV138248F6">Fig. 6</xref>K). These experiments demonstrated a significant decrease only in the DMS in <italic>He</italic><sup>−/−</sup> mice compared with wt mice (<xref ref-type="fig" rid="DEV138248F6">Fig. 6</xref>E-H). Interestingly, a specific alteration of the ENK<sup>+</sup> population was also observed in the DMS in the absence of <italic>He</italic> (<xref ref-type="fig" rid="DEV138248F6">Fig. 6</xref>I). However, no differences were found for the SP<sup>+</sup> population in <italic>He</italic><sup>−/−</sup> mice compared with wt mice (<xref ref-type="fig" rid="DEV138248F6">Fig. 6</xref>J). In addition, no differences were observed between genotypes in the cholinergic and parvalbumin<sup>+</sup> striatal interneurons (<uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S16F,G</uri>; <xref ref-type="fig" rid="DEV138248F6">Fig. 6</xref>C,D).
<fig id="DEV138248F6" orientation="portrait" position="float"><label>Fig. 6.</label><caption><p><bold>Lack of <italic>He</italic> during development alters the number of mature MSNs in adult <italic>He</italic><sup>−/−</sup> mice.</bold> (A-J) Stereological cell counts of neuronal striatal populations in wt and <italic>He</italic><sup>−/−</sup> mice striatum. (A) The total number of striatal calbindin<sup>+</sup> cells is reduced in <italic>He</italic><sup>−/−</sup> adult mice compared with wt adult mice. (B) The total number of striatal DARPP-32<sup>+</sup> cells is reduced in <italic>He</italic><sup>−/−</sup> adult mice compared with wt adult mice. (C,D) The total number of striatal ChAT<sup>+</sup> (C) or parvalbumin<sup>+</sup> (D) cells is not altered between wt and <italic>He</italic><sup>−/−</sup> adult mice. (E-H) The total number of striatal DARPP-32<sup>+</sup> cells is specifically reduced in the DMS (E) in <italic>He</italic><sup>−/−</sup> adult mice compared with wt adult mice. No differences are found in the DLS (F), VMS (G) and VLS (H) between both genotypes. (I) The total number of ENK<sup>+</sup> cells is reduced in the DMS of <italic>He</italic><sup>−/−</sup> compared with wt mice. (J) The total number of SP<sup>+</sup> cells is not altered in the DMS between wt and <italic>He</italic><sup>−/−</sup> mice. (K) Schematic showing the division of a coronal striatal section into DMS, DLS, VMS and VLS regions. Results represent the mean±s.e.m. of 4-5 mice per condition. Statistical analysis was performed by using Student's <italic>t</italic>-test; *<italic>P</italic><0.05, **<italic>P</italic><0.005.</p></caption><graphic xlink:href="develop-144-138248-g6"></graphic></fig></p><p>In order to study the direct involvement of He in the acquisition of a mature MSN phenotype, we transplanted eGFP or <italic>He</italic>-overexpressing NPCs into the mouse neonatal forebrain (<xref ref-type="fig" rid="DEV138248F7">Fig. 7</xref>A). Compared with control cells, <italic>He</italic>-overexpressing cells displayed more robust branching 2 weeks post-transplantation (total neurite tree length per neuron: GFP 168.13±21.92 µm, <italic>He</italic> 413.66±98.84 µm, <italic>P</italic>=0.0046; number of branches per neuron: GFP 14.43±1.68, <italic>He</italic> 24.89±4.08, <italic>P</italic>=0.0089; <xref ref-type="fig" rid="DEV138248F7">Fig. 7</xref>B-E) and DARPP-32 expression was observed in few scattered cells adjacent to the striatum (<xref ref-type="fig" rid="DEV138248F7">Fig. 7</xref>G,H). Four weeks post-transplantation, several <italic>He</italic>-overexpressing cells displayed DARPP-32 expression (<xref ref-type="fig" rid="DEV138248F7">Fig. 7</xref>J-L), in contrast to control cells, which were all DARPP-32 negative (<xref ref-type="fig" rid="DEV138248F7">Fig. 7</xref>I). Quantification of DARPP-32<sup>+</sup> neurons in GFP transplanted cells demonstrated a 150-fold increase in the number of double-stained cells in He-expressing cells compared with controls. In addition, <italic>He</italic> overexpression in striatal primary cultures significantly increased the number of calbindin<sup>+</sup>, DARPP-32<sup>+</sup> and ENK<sup>+</sup> cells (<uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S17</uri>).
<fig id="DEV138248F7" orientation="portrait" position="float"><label>Fig. 7.</label><caption><p><bold><italic>He</italic> induces an MSN phenotype <italic>in vivo</italic>.</bold> (A) Schematic of the transplantation of eGFP and <italic>He</italic>-overexpressing NPCs into the mouse neonatal forebrain. (B-H) Representative images of forebrain coronal sections containing grafted cells 2 weeks post-transplantation, immunostained for GFP and DARPP-32. Compared with control cells (B,D), <italic>He</italic> overexpressing cells display more robust branching (C,E) and a few of them start to express DARPP-32 (G,H). (I-L) Representative images of grafted cells 4 weeks post-transplantation, labeled for GFP and DARPP-32. In contrast to control cells (I), several <italic>He</italic> overexpressing cells display DARPP-32 expression (J-L), indicative of the acquisition of a striatal MSN fate. Scale bars: 50 µm (B,C); 20 µm (D-G,I,J); 10 µm (H,K,L).</p></caption><graphic xlink:href="develop-144-138248-g7"></graphic></fig></p></sec><sec id="s2e"><title><italic>He</italic> loss disturbs the acquisition of motor skills</title><p>To analyze the functional implication of <italic>He</italic> loss, we assessed the performance of motor tasks in wt and <italic>He</italic><sup>−/−</sup> mice (<xref ref-type="fig" rid="DEV138248F8">Fig. 8</xref>). In the simple swimming test, <italic>He<sup>−/−</sup></italic> mice displayed significant abnormalities compared with wt mice in their swimming latency in the first testing trial (genotype: <italic>F</italic><sub>2,162</sub>=4.08, <italic>P</italic><0.05; post-hoc trial 1: <italic>P</italic><0.01), but these disappeared over subsequent trials (<xref ref-type="fig" rid="DEV138248F8">Fig. 8</xref>A).
<fig id="DEV138248F8" orientation="portrait" position="float"><label>Fig. 8.</label><caption><p><bold>The acquisition of new motor skills is impaired in <italic>He<sup>−/−</sup></italic> mice.</bold> (A-C) Motor coordination and balance were analyzed in wt and <italic>He<sup>−/−</sup></italic> mice by performing the simple swimming test (A), the balance beam (B) and the rotarod task (C). Values are expressed as mean±s.e.m. of 7-8 mice per condition. Data were analyzed by two-way ANOVA and Bonferroni's post-hoc test. *<italic>P</italic><0.05, **<italic>P</italic><0.005, ***<italic>P</italic><0.001.</p></caption><graphic xlink:href="develop-144-138248-g8"></graphic></fig></p><p>In addition, wt and <italic>He<sup>−/−</sup></italic> mice progressively improved their performance in the balance beam along four trials (trial: <italic>F</italic><sub>3,112</sub>=14.66, <italic>P</italic><0.001). However, <italic>He<sup>−/−</sup></italic> mice fell off more times than controls during the first trials (genotype: <italic>F</italic><sub>2,112</sub>=13.52, <italic>P</italic><0.01; post-hoc trial 1: <italic>P</italic><0.001; post-hoc trial 2: <italic>P</italic><0.01; <xref ref-type="fig" rid="DEV138248F8">Fig. 8</xref>B).</p><p>In the rotarod test, all mice reached a stable level of performance within six trials (<xref ref-type="fig" rid="DEV138248F8">Fig. 8</xref>C), as measured by a decrease in the number of falls in 60 s per mouse (testing trial <italic>F</italic><sub>5,138</sub>=15.87, <italic>P</italic><0.01). However, acquisition on the rotarod task was significantly delayed in <italic>He<sup>−/−</sup></italic> compared with wt mice (genotype <italic>F</italic><sub>2,138</sub>=21.03, <italic>P</italic><0.01).</p></sec></sec><sec sec-type="discussion" id="s3"><title>DISCUSSION</title><p>Striatal MSNs are generated from NPCs located at the GZ of the LGE. Here, we show that He regulates late striatal neurogenesis that gives rise to D2R<sup>+</sup> ENK neurons. He is expressed by NPCs in the G<sub>1</sub>/G<sub>0</sub> cell cycle phase at the GZ, impairing the G<sub>1</sub>-S transition by the regulation of cyclin E, which in turn induces neuronal differentiation. Consequently, lack of <italic>He</italic> produces an extended S phase and cell cycle length that increases the number of proliferating NPCs at the GZ. At the beginning of the postnatal period, the number of these NPCs is reduced due to their late aberrant neurogenesis that results in cell death. These abnormalities of embryonic development in <italic>He</italic><sup>−/−</sup> mice produce a reduction of a specific subset of striatopallidal neurons of the dorsomedial striatum that control motor skill learning.</p><sec id="s3a"><title><italic>He</italic> is necessary for striatopallidal neurogenesis</title><p>NPCs located at the GZ of the LGE become postmitotic and migrate into the MZ to acquire the MSN phenotype (<xref rid="DEV138248C8" ref-type="bibr">Brazel et al., 2003</xref>). We have previously proposed a model for the development of striatal subpopulations in which Ikaros and He are involved in the development of striatopallidal ENK<sup>+</sup> matrix MSNs (<xref rid="DEV138248C48" ref-type="bibr">Martín-Ibáñez et al., 2012</xref>). This hypothesis is reinforced by the localization of <italic>He</italic> in ENK<sup>+</sup> neurons that co-express D2R (present results). Besides the apparent similar function between He and Ikaros on ENK<sup>+</sup> neurogenesis, there is much evidence that they determine different ENK<sup>+</sup> subpopulations. They are expressed by different cells (<xref rid="DEV138248C48" ref-type="bibr">Martín-Ibáñez et al., 2012</xref>), and their expression is not modified in the reciprocal knockout mice (<xref rid="DEV138248C47" ref-type="bibr">Martín-Ibáñez et al., 2010</xref>, <xref rid="DEV138248C48" ref-type="bibr">2012</xref>). These results are contrary to the role of Ikaros family members in the hematopoietic system where they directly interact (<xref rid="DEV138248C28" ref-type="bibr">Hahm et al., 1998</xref>; <xref rid="DEV138248C31" ref-type="bibr">John et al., 2009</xref>), suggesting specific mechanisms of action in each system.</p></sec><sec id="s3b"><title>He regulates neurogenesis through the control of the G1-S phase checkpoint</title><p><italic>Gsx2</italic><sup>+</sup> radial glial cells constitute the first NPCs that appear during LGE ontogeny, which differentiate with the onset of the neurogenesis from the neuroephithelial cells (for a review, see <xref rid="DEV138248C13" ref-type="bibr">Dimou and Götz, 2014</xref>). <italic>He-</italic>expressing cells are derived from radial glial cells, as its expression disappears in <italic>Gsx2</italic> knockout mice (<xref rid="DEV138248C48" ref-type="bibr">Martín-Ibáñez et al., 2012</xref>). However, <italic>He</italic> loss does not compromise the number of the radial glial cell subtypes described elsewhere (<xref rid="DEV138248C61" ref-type="bibr">Pilz et al., 2013</xref>). Radial glial cells generate the large MSNs output by a series of intermediate NPCs to amplify specific lineages, although these striatal NPCs are still poorly characterized. <italic>He</italic> is expressed by a small number of NPCs distributed in deep SVZ. Although the localization of <italic>He</italic> is mainly at the dorsal areas, it does not seem to be defining a specific SVZ domain as it has been described for other transcription factors in the VZ (<xref rid="DEV138248C19" ref-type="bibr">Flames et al., 2007</xref>).</p><p>Some of the NPCs that express <italic>He</italic> at the GZ co-express low levels of Ki67. Considering that Ki67 labels cells during all phases of the cell cycle except G<sub>0</sub> (<xref rid="DEV138248C33" ref-type="bibr">Kanthan et al., 2010</xref>; <xref rid="DEV138248C66" ref-type="bibr">Scholzen and Gerdes, 2000</xref>) and that G<sub>1</sub> is the cell cycle phase with lower Ki67 expression levels (<xref rid="DEV138248C43" ref-type="bibr">Lopez et al., 1991</xref>), we hypothesized that <italic>He</italic> is expressed in a subset of NPCs during G<sub>1</sub> and G<sub>0</sub> phases. The lack of colocalization between <italic>He</italic> and BrdU or PH3 reinforces the idea that <italic>He</italic> is not expressed by cells at S or M phases, respectively. Within G<sub>1</sub> phase He impairs S-phase entry, reducing S-phase length and arresting NPCs at G<sub>1</sub>/G<sub>0</sub> phase to facilitate neuronal differentiation. Consequently, <italic>He</italic><sup>−/−</sup> mice NPCs increase S-phase entry and continue proliferating in the striatal GZ impairing neurogenesis (see <uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S18</uri> for a representative scheme). Similarly, Lacomme and co-workers demonstrated that Ngn2 regulates G<sub>1</sub>-S phase transition, blocking S-phase entry and increasing the number of NPCs at G<sub>1</sub>/G<sub>0</sub> phase (<xref rid="DEV138248C38" ref-type="bibr">Lacomme et al., 2012</xref>). In addition, NPCs shorten S phase on commitment to neuron production (<xref rid="DEV138248C4" ref-type="bibr">Arai et al., 2011</xref>; <xref rid="DEV138248C71" ref-type="bibr">Turrero García et al., 2015</xref>). Thus, cell cycle length and G<sub>1</sub>-S phase transition are crucial processes for neurogenesis and both are regulated by He. We hypothesize that He arrests LGE-derived NPCs into phases G<sub>1</sub>/G<sub>0</sub> to allow the accumulation of the protein machinery necessary for their differentiation to specific striatal neurons. In fact, crucial aspects of neural commitment are acquired in the final division cycle of NPCs. For example, the cortical laminar fate of NPC is acquired during the final progenitor cell division (<xref rid="DEV138248C6" ref-type="bibr">Bohner et al., 1997</xref>; <xref rid="DEV138248C15" ref-type="bibr">Edlund and Jessell, 1999</xref>; <xref rid="DEV138248C50" ref-type="bibr">McConnell and Kaznowski, 1991</xref>). Similarly, during motor neuron development, NPCs become sonic hedgehog (Shh) dependent late in their final progenitor cell cycle (<xref rid="DEV138248C18" ref-type="bibr">Ericson et al., 1996</xref>), which commits them to a motor neuronal fate (<xref rid="DEV138248C70" ref-type="bibr">Tanabe et al., 1998</xref>).</p><p>G<sub>1</sub>-S phase transition is regulated by Cdk2 and cyclin E, which form a complex that participates in G<sub>1</sub>-S phase checkpoint (reviewed by <xref rid="DEV138248C30" ref-type="bibr">Hardwick and Philpott, 2014</xref>; <xref rid="DEV138248C57" ref-type="bibr">Ohtsubo and Roberts, 1993</xref>). Our results suggest that cyclin E is a key factor regulated by He that correlates with the G<sub>1</sub>-S phase transition impairment observed in the <italic>He<sup>−/−</sup></italic> mice. In fact, the cyclin E gene (<italic>Ccne1</italic>) has two very strong He-binding domains (<xref rid="DEV138248C35" ref-type="bibr">Kim et al., 2015</xref>) suggesting a direct regulation. Similar to our results, Pilaz and colleagues described that overexpression of cyclin E in cortical NPCs promotes a proliferation increase whereas downregulation of cyclin E led to a decrease in progenitor proliferation (<xref rid="DEV138248C60" ref-type="bibr">Pilaz et al., 2009</xref>). In addition, a direct correlation between cyclin E and S-phase entry was proposed by ectopic expression of cyclin E, which shortens the G<sub>1</sub> interval and increases the length of S phase by advancing G<sub>1</sub>-S phase transition (<xref rid="DEV138248C64" ref-type="bibr">Resnitzky et al., 1994</xref>). Furthermore, ectopic expression of cyclin E can drive G<sub>1</sub> cells into S phase under conditions in which Rb is not phosphorylated and E2F is not activated (<xref rid="DEV138248C40" ref-type="bibr">Leng et al., 1997</xref>; <xref rid="DEV138248C46" ref-type="bibr">Lukas et al., 1997</xref>). This is in agreement with our results, as we observed an increase in cyclin E but no alterations in phosphorylated RB or E2F in <italic>He<sup>−/−</sup></italic> mice.</p></sec><sec id="s3c"><title><italic>He</italic> loss increases postnatal cell death</title><p>The homeostasis of NPCs in the striatum is a regulated process in which neurogenesis precedes astro-gliogenesis during development (<xref rid="DEV138248C3" ref-type="bibr">Alvarez-Buylla et al., 2001</xref>; <xref rid="DEV138248C55" ref-type="bibr">Ninkovic and Götz, 2013</xref>). However, contrary to the increase of astro-gliogenesis observed in <italic>Ikaros<sup>−/−</sup></italic> mice (<xref rid="DEV138248C47" ref-type="bibr">Martín-Ibáñez et al., 2010</xref>), we could not detect any effects on glial cells in <italic>He<sup>−/−</sup></italic> mice. The role of He in neurogenesis through cyclin E-mediated G1-S transition without modifying astro-gliogenesis coincides with the effect of deferoxamine, a G<sub>1</sub>/S-phase blocker, which increases neuronal but not astrocytic NPC differentiation (<xref rid="DEV138248C34" ref-type="bibr">Kim et al., 2006</xref>; <xref rid="DEV138248C53" ref-type="bibr">Misumi et al., 2008</xref>).</p><p>The reduction of NPCs in <italic>He<sup>−/−</sup></italic> mice at postnatal stages can be related to the increase in cell death during this period. Naturally occurring cell death is a crucial step in re-defining the final size of specific neuronal populations (<xref rid="DEV138248C9" ref-type="bibr">Burek and Oppenheim, 1996</xref>; <xref rid="DEV138248C37" ref-type="bibr">Kristiansen and Ham, 2014</xref>), which directly correlates with the time of prior exit from cell cycle and position during neuronal development (<xref rid="DEV138248C26" ref-type="bibr">Gould et al., 1999</xref>). Our results point to the idea that the cell death observed in <italic>He</italic><sup>−/−</sup> mice is a consequence of the delay in NPCs exiting cell cycle around E18.5, then migrating into the MZ where they become neurons and die. Therefore, lack of He produces a dysfunction in the time and position of late-generated neurons in the MZ. Dual effects have also been described for Isl1 and Ebf1, which promote differentiation of striatonigral neurons and in their absence striatal cell death is observed (<xref rid="DEV138248C21" ref-type="bibr">Garel et al., 1999</xref>; <xref rid="DEV138248C44" ref-type="bibr">Lu et al., 2014</xref>). Taken together, all these results indicate that He loss causes aberrant neurogenesis, which in turn induces neuronal cell death compromising striatal development.</p></sec><sec id="s3d"><title>He participates in the differentiation of a subset of MSNs that is involved in early motor learning</title><p>He-mediated regulation of the NPC cell cycle correlates with the determination of a subset of striatopallidal MSNs. The events occurring during striatal development of <italic>He<sup>−/−</sup></italic> mice cause a specific reduction of striatal MSNs in the DMS in the adulthood. Taken together, our present findings demonstrate that He plays a direct role in the commitment of NPCs to MSNs. Accordingly, <italic>He</italic> overexpression is sufficient to differentiate NPCs transplanted into the striatum in MSNs expressing DARPP-32.</p><p>Previously published works and reviews suggest that striatal motor function is involved with habit formation (<xref rid="DEV138248C76" ref-type="bibr">Yin and Knowlton, 2006</xref>) and procedural learning (<xref rid="DEV138248C36" ref-type="bibr">Kreitzer, 2009</xref>), which fits with what we see in our <italic>He<sup>−/−</sup></italic> mice. The striatum has been classically divided into dorsal and ventral areas, the dorsal being the most involved in motor behavior (<xref rid="DEV138248C14" ref-type="bibr">Durieux et al., 2012</xref>). Accumulating evidence shows anatomical and functional differences in the striatum between the external DLS and the internal DMS (<xref rid="DEV138248C14" ref-type="bibr">Durieux et al., 2012</xref>; <xref rid="DEV138248C27" ref-type="bibr">Graybiel, 2008</xref>; <xref rid="DEV138248C74" ref-type="bibr">Voorn et al., 2004</xref>). Interestingly, the DMS is involved in the initial stages of motor skill learning (<xref rid="DEV138248C32" ref-type="bibr">Jueptner and Weiller, 1998</xref>; <xref rid="DEV138248C45" ref-type="bibr">Luft and Buitrago, 2005</xref>), whereas the DLS is required for progressive skill automatization and habit learning (<xref rid="DEV138248C54" ref-type="bibr">Miyachi et al., 2002</xref>; <xref rid="DEV138248C77" ref-type="bibr">Yin et al., 2004</xref>). In addition, it has been shown that the loss of D2R<sup>+</sup> neurons in the DMS produces early motor learning impairment but the animals can improve their performances to reach control levels (<xref rid="DEV138248C14" ref-type="bibr">Durieux et al., 2012</xref>). As <italic>He<sup>−/−</sup></italic> mice show impairments in the acquisition of motor skills, it seems plausible that He is involved in the generation of a specific subpopulation of striatopallidal D2R<sup>+</sup> MSNs in the DMS. The cerebellum is also involved in fine-tuning the motor agility found in procedural skills. Cerebellar lesions or dysfunctions produce permanent deficits in motor tasks. However, diseased animals never perform motor tasks as well as their control or wt littermates (<xref rid="DEV138248C65" ref-type="bibr">Sausbier et al., 2004</xref>; <xref rid="DEV138248C67" ref-type="bibr">Stroobants et al., 2013</xref>; <xref rid="DEV138248C73" ref-type="bibr">Vinueza Veloz et al., 2012</xref>). As <italic>He<sup>−/−</sup></italic> mice show problems in the acquisition but not the execution of motor skills it seems that an association with cerebellar deficits is not likely.</p></sec><sec id="s3e"><title>Conclusion</title><p>In conclusion, our results demonstrate a novel mechanism for He in the development of striatopallidal MSNs of the DMS that controls motor skills learning. He exerts its main effects on the commitment of NPCs to MSNs through the regulation of the G<sub>1</sub>-S phase transition and arrests NPCs at G<sub>1</sub> phase to induce neuronal differentiation. The alterations of this mechanism observed in <italic>He<sup>−/−</sup></italic> mice produce aberrant neurogenesis leading to the cell death of late-generated neurons.</p></sec></sec><sec sec-type="methods" id="s4"><title>MATERIALS AND METHODS</title><sec id="s4a"><title>Animals</title><p>B6CBA wild-type (wt) mice (from Charles River Laboratories, Les Oncins, France), <italic>He</italic> knockout mice (<italic>He</italic><sup>−/−</sup>) (<xref rid="DEV138248C10" ref-type="bibr">Cai et al., 2009</xref>), pCAGs-eGFP (<xref rid="DEV138248C59" ref-type="bibr">Okabe et al., 1997</xref>), D1R-eGFP and D2R-eGFP generated by GENSAT (<xref rid="DEV138248C24" ref-type="bibr">Gong et al., 2003</xref>) were used. For further details of mice strains and genotyping, see the <uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">supplementary Materials and Methods</uri>.</p></sec><sec id="s4b"><title>Birthdating, proliferation and tracking experiments <italic>in vivo</italic></title><p>Birthdating experiments were performed as described elsewhere (<xref ref-type="fig" rid="DEV138248F1">Fig. 1</xref>B; <xref rid="DEV138248C47" ref-type="bibr">Martín-Ibáñez et al., 2010</xref>). To study the generation of He<sup>+</sup> cells, injections of EdU (50 mg/kg) at E13.5 or E14.5, or BrdU at E16.5 into wt pregnant mice were performed and allowed to develop until E18.5, when embryos were processed for He and BrdU immunohistochemistry or EdU detection (Life Technologies) (<uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S4A</uri>).</p><p>To analyze <italic>in vivo</italic> proliferation in the GZ, E14.5 pregnant mice received a single dose of EdU (50 mg/kg). The proliferation analysis of E16.5, P3 and P7 was performed by Ki67 immunohistochemistry.</p><p>In order to track the origin of dead cells in the MZ, a pulse of EdU (50 mg/kg) was performed at E18.5, and immunohistochemistry was performed at P3 against EdU and cleaved caspase 3 (Cell Signaling Technology), nestin, GFAP or NeuN (<xref ref-type="fig" rid="DEV138248F5">Fig. 5</xref>G).</p><p>To study whether the lack of <italic>He</italic> could alter the cells entering the S phase of the cell cycle, we performed <italic>in vivo</italic> experiments with <italic>He</italic><sup>−/−</sup> and wt mice as previously described (<xref rid="DEV138248C39" ref-type="bibr">Lange et al., 2009</xref>) (<xref ref-type="fig" rid="DEV138248F4">Fig. 4</xref>K).</p><p>For further details of these methods, see the <uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">supplementary Materials and Methods</uri>.</p></sec><sec id="s4c"><title>Production of viral particles and cell transduction</title><p>To overexpress <italic>He</italic>, NPCs were transduced with the pLV-<italic>HE</italic>-IRES-eGFP plasmid or the pLV-IRES-eGFP plasmid, which encode human <italic>HE</italic> and eGFP or eGFP alone, respectively. For further details of viral particle production, see the <uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">supplementary Materials and Methods</uri>.</p></sec><sec id="s4d"><title>Neurosphere assay</title><p>LGEs from E14.5 wt or <italic>He<sup>−/−</sup></italic> mice were dissected out and mechanically disaggregated to culture as neurosphere and differentiate to neural cells as described previously (<xref rid="DEV138248C47" ref-type="bibr">Martín-Ibáñez et al., 2010</xref>). For further details of neurosphere cultures, see the <uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">supplementary Materials and Methods</uri>.</p><p>Loss-of-function (LOF) experiments were performed with neurospheres derived from <italic>He<sup>−/−</sup></italic> mice whereas gain-of-function (GOF) experiments were performed by overexpressing <italic>He</italic>. The number of neurons (β-III-tubulin<sup>+</sup>) and astrocytes (GFAP<sup>+</sup>) were analyzed after 6 days of differentiation.</p></sec><sec id="s4e"><title>Cell cycle analysis <italic>in vitro</italic></title><sec id="s4e1"><title>Proliferation assays</title><p>BrdU incorporation assays were performed in wt and <italic>He<sup>−/−</sup></italic> mice-derived neurospheres (LOF) and neurospheres overexpressing <italic>He</italic> (GOF) as described elsewhere (<xref rid="DEV138248C72" ref-type="bibr">Urbán et al., 2010</xref>). The number of Ki67<sup>+</sup> cells was also analyzed in wt and <italic>He<sup>−/−</sup></italic> mice-derived neurospheres (LOF) and neurospheres overexpressing <italic>He</italic> (GOF).</p></sec><sec id="s4e2"><title>Cell cycle length</title><p>An accumulative exposure to 1 µM BrdU over 36 h was performed in wt and <italic>He</italic><sup>−/−</sup> mice-derived neurospheres (LOF) and in neurospheres overexpressing <italic>He</italic> (GOF) after 2 DIV in proliferation. Cells were fixed at different time points after 1 µM BrdU exposure (1, 3, 6, 12, 24 and 36 h) and processed for BrdU immunocytochemistry. Following regression analysis as previously described by <xref rid="DEV138248C68" ref-type="bibr">Takahashi et al. (1992</xref>, <xref rid="DEV138248C69" ref-type="bibr">1995</xref>), the length of the cell cycle and the length of the S phase were calculated for the NPCs.</p></sec><sec id="s4e3"><title>S-phase analysis</title><p>To study the cells entering and exiting the S phase of the cell cycle, we performed <italic>in vitro</italic> experiments with neurospheres derived from <italic>He</italic><sup>−/−</sup> and wt mice as described previously (<xref rid="DEV138248C39" ref-type="bibr">Lange et al., 2009</xref>) (<xref ref-type="fig" rid="DEV138248F3">Fig. 3</xref>E-H).</p></sec><sec id="s4e4"><title>G<sub>2</sub>/M phase labeling</title><p>To study the combined length of the G<sub>2</sub>/M phases, an accumulative exposure to 1 µM BrdU over 5 h was performed after 2 DIV in proliferation to analyze the mitotic BrdU labeling index as described previously (<xref rid="DEV138248C69" ref-type="bibr">Takahashi et al., 1995</xref>).</p></sec><sec id="s4e5"><title>Cell cycle index</title><p>We analyzed cell cycle index as the number of cells that incorporate BrdU but leave the cell cycle (i.e. abandoned the G<sub>1</sub>-S-G<sub>2</sub>/M phases and entered into G<sub>0</sub>) as previously described (<xref rid="DEV138248C72" ref-type="bibr">Urbán et al., 2010</xref>) (<uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">Fig. S13</uri>).</p></sec><sec id="s4e6"><title>Discerning high and low Ki67-expressing cells</title><p>We detected cells expressing high and low levels of Ki67 using the automatic intensity detection of the Cell Profiler software.</p><p>For further details of cell cycle analyses, see the <uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">supplementary Materials and Methods</uri>.</p></sec></sec><sec id="s4f"><title>Analysis of He-binding sites at the <italic>Ccne1</italic> promoter</title><p>We obtained and analyzed the Big Wig file deposited in Gene Expression Omnibus by <xref rid="DEV138248C35" ref-type="bibr">Kim et al. (2015)</xref>, and visualized it in the Integrative Genome Viewer with the files provided aligned to the Ensembl Mouse Genome. Details of database used can be found in the <uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">supplementary Materials and Methods</uri>.</p></sec><sec id="s4g"><title>Western blots</title><p>We performed western blot analyses for cyclin E and PCNA as described elsewhere (<xref rid="DEV138248C11" ref-type="bibr">Canals et al., 2004</xref>) in wt and <italic>He</italic><sup>−/−</sup> mice-derived neurospheres (LOF) and neurospheres overexpressing <italic>He</italic> (GOF). E2F1 and retinoblastoma (Rb) were detected in LOF experiments. For further details of western blot procedure, see the <uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">supplementary Materials and Methods</uri>.</p></sec><sec id="s4h"><title><italic>In situ</italic> hybridization</title><p>To assess which striatal subpopulation of MSNs express <italic>He</italic>, we performed double <italic>in situ</italic> hybridization for ENK or tachykinin A (<italic>Tac1</italic>, a precursor of SP), the precursor of SP, and immunohistochemistry for He as described previously (<xref rid="DEV138248C47" ref-type="bibr">Martín-Ibáñez et al., 2010</xref>). For further details of <italic>in situ</italic> procedures, see the <uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">supplementary Materials and Methods</uri>.</p></sec><sec id="s4i"><title>Immunolabeling</title><p>For histological preparations, embryonic or postnatal brains were removed at specific developmental stages and were frozen in dry ice-cooled methylbutane or cryoprotected depending on the procedure. Immunolabeling was performed according to the protocols described by <xref rid="DEV138248C7" ref-type="bibr">Bosch et al. (2004)</xref> and <xref rid="DEV138248C11" ref-type="bibr">Canals et al. (2004)</xref>. For further details of the antibodies used and immunostaining procedures, see the <uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">supplementary Materials and Methods</uri>.</p></sec><sec id="s4j"><title>Measurement of volumes and <italic>in vivo</italic> cell counts</title><p>The volumes of certain brain regions were measured using ImageJ v1.33 as described previously (<xref rid="DEV138248C11" ref-type="bibr">Canals et al., 2004</xref>). All cell counts [EdU and Ki67 for GZ proliferation; BrdU for birthdating experiments; cleaved caspase 3 for cell death; <italic>Ctip2</italic>, calbindin, DARPP-32, choline acetyl transferase (ChAT) and parvalbumin for striatal cell population] were performed blind to genotype. Unbiased stereological counts were performed for all striatal areas for each animal. DMS, DLS, VMS and VLS were specifically counted for DARPP-32-, ENK- and SP-positive cells.</p><p>The distribution of mitosis in <italic>He<sup>−/−</sup></italic> and wt striatum at E16.5 was analyzed as described by <xref rid="DEV138248C61" ref-type="bibr">Pilz et al. (2013)</xref> and counted using CAST software.</p><p>Automated quantification of branches, and neurite length was performed using Cell Profiler v2.8 software.</p><p>For further details of cell counts, see the <uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">supplementary Materials and Methods</uri>.</p></sec><sec id="s4k"><title>Q-PCR</title><p>Gene expression was evaluated by Q-PCR assays as previously described by <xref rid="DEV138248C47" ref-type="bibr">Martín-Ibáñez et al. (2010)</xref>. For further details of the probes used and PCR procedures, see the <uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">supplementary Materials and Methods</uri>.</p></sec><sec id="s4l"><title>Primary striatal culture and transfection</title><p>E14.5 fetal LGEs were dissected and cultured as previously described (<xref rid="DEV138248C47" ref-type="bibr">Martín-Ibáñez et al., 2010</xref>). For <italic>He</italic> overexpression studies, cells were transfected with the MSCV-<italic>He</italic>-IRES-eGFP plasmid, or with the MSCV-IRES-eGFP plasmid as a control (<xref rid="DEV138248C80" ref-type="bibr">Zhang et al., 2007</xref>). We counted the number of <italic>He</italic> or eGFP overexpressing cells that colocalized with calbindin, DARPP-32 or ENK. For further details of primary culture methods, see the <uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">supplementary Materials and Methods</uri>.</p></sec><sec id="s4m"><title>Cell transplants</title><p>Unilateral striatal injections of <italic>He</italic>-overexpressing cells were performed using a stereotaxic apparatus (Davis Kopf Instruments, Tujunga, CA, USA); coordinates (mm): AP, +2.3, L, +1.4 from lambda and DV, −1.8 from dura. For further details of cell transplants, see the <uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">supplementary Materials and Methods</uri>.</p></sec><sec id="s4n"><title>Mouse behavior</title><sec id="s4n1"><title>Swimming task</title><p>The mice were placed at the end of a transparent perspex extended swimming tank facing away from a visible escape platform at one end of the tank and the time taken to reach the platform was recorded.</p></sec><sec id="s4n2"><title>Balance beam</title><p>Animals were allowed to walk along a horizontally placed beam of a long steel cylinder (50 cm) with 15 mm diameter. Latency to fall and number of falls were measured.</p></sec><sec id="s4n3"><title>Rotarod</title><p>Acquisition of a motor coordination task was further evaluated on the rotarod apparatus (24 rpm). Latency to fall and the number of falls during 60 s was recorded.</p><p>For further details of mouse behavior analyses, see the <uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">supplementary Materials and Methods</uri>.</p></sec></sec><sec id="s4o"><title>Statistical analysis</title><p>All results are expressed as the mean of independent experiments±s.e.m. Results were analyzed using Student's <italic>t</italic>-test or one-way or two-way ANOVA, followed by the Bonferroni post-hoc test.</p></sec></sec></body><back><ack><title>Acknowledgements</title><p>The authors are very grateful to Dr Phil Sanders for critical reading of the manuscript, Dr David Vanneste for project managing and Ana López for technical assistance. We are also grateful to Dr Christopher A. Klug (Department of Microbiology, Division of Developmental and Clinical Immunology, University of Alabama at Birmingham, USA) for the MSCV-IRES-eGFP and MSCV-<italic>He</italic>-IRES-eGFP plasmids; Dr Pantelis Tsoulfas (University of Miami, FL, USA) for the pRRLsinPPT plasmids; and Dr Stephen T. Smale (Howard Hughes Medical Institute, Molecular Biology Institute, and Department of Microbiology and Immunology, UCLA School of Medicine, Los Angeles, CA, USA) for the anti-He antibody. The Rat-401 monoclonal anti-nestin antibody developed by S. Hockfield was obtained from the Development Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by the Department of Biological Science, University of Iowa, Iowa City, IA, USA.</p></ack><fn-group><fn fn-type="COI-statement"><p><bold>Competing interests</bold></p><p>The authors declare no competing or financial interests.</p></fn><fn><p><bold>Author contributions</bold></p><p>R.M.-I. and M.P.: conceived this study, designed and performed experiments, analyzed data and prepared manuscript; A.G., A.M., I.G., L.M.-P., C.H., M.E. and G.G.-D.B.: performed experiments and analyzed data; M.J.E., C.V.-A., J.A., J.-A.G., S.C. and P.K.: contributed reagents/materials/analysis tools; J.M.C.: supervised and conceived this study, analyzed data and edited the manuscript.</p></fn><fn fn-type="financial-disclosure"><p><bold>Funding</bold></p><p>This study was supported by grants from the Ministerio de Economía y Competitividad (BFU2010-19630 to C.V.-A.; SAF 2014-57160-R, to J. A.; SAF2015-66505-R to J.M.C.), and Instituto de Salud Carlos III-Subdirección General de Evaluación, and European Regional Development Fund (ERDF) [CIBERNED, to J. A and C.V.-A.; and RETICS (RD12/0019/0002; Red de Terapia Celular), to J.M.C.], Spain; Generalitat de Catalunya (2014SGR-968 to J.A.); Fundació la Marató de TV3 (20140130/1 to J.A.); and CHDI Foundation (A-7332 to J.M.C.). M.P. was a fellow from the Generalitat de Catalunya, Spain and E.C. was a fellow of the Ministerio de Economía y Competitividad, Spain. This work has been developed in the context of ADVANCE(CAT) with the support of ACCIÓ (Catalonia Trade & Investment; Generalitat de Catalunya) and the European Community under the Catalonian European Regional Development Fund operational program 2014-2020. Deposited in PMC for immediate release.</p></fn><fn fn-type="supplementary-material"><p><bold>Supplementary information</bold></p><p>Supplementary information available online at <uri xlink:href="http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental">http://dev.biologists.org/lookup/doi/10.1242/dev.138248.supplemental</uri></p></fn></fn-group><ref-list><title>References</title><ref id="DEV138248C1"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Agoston</surname><given-names>D. V.</given-names></name>, <name name-style="western"><surname>Szemes</surname><given-names>M.</given-names></name>, <name name-style="western"><surname>Dobi</surname><given-names>A.</given-names></name>, <name name-style="western"><surname>Palkovits</surname><given-names>M.</given-names></name>, <name name-style="western"><surname>Georgopoulos</surname><given-names>K.</given-names></name>, <name name-style="western"><surname>Gyorgy</surname><given-names>A.</given-names></name> and <name name-style="western"><surname>Ring</surname><given-names>M. A.</given-names></name></person-group> (<year>2007</year>). <article-title>Ikaros is expressed in developing striatal neurons and involved in enkephalinergic differentiation</article-title>. <source><italic>J. Neurochem.</italic></source><volume>102</volume>, <fpage>1805</fpage>-<lpage>1816</lpage>. <pub-id pub-id-type="doi">10.1111/j.1471-4159.2007.04653.x</pub-id><pub-id pub-id-type="pmid">17504264</pub-id></mixed-citation></ref><ref id="DEV138248C2"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Alsiö</surname><given-names>J. M.</given-names></name>, <name name-style="western"><surname>Tarchini</surname><given-names>B.</given-names></name>, <name name-style="western"><surname>Cayouette</surname><given-names>M.</given-names></name> and <name name-style="western"><surname>Livesey</surname><given-names>F. J.</given-names></name></person-group> (<year>2013</year>). <article-title>Ikaros promotes early-born neuronal fates in the cerebral cortex</article-title>. <source><italic>Proc. Natl. Acad. Sci. USA</italic></source><volume>110</volume>, <fpage>E716</fpage>-<lpage>E725</lpage>. <pub-id pub-id-type="doi">10.1073/pnas.1215707110</pub-id><pub-id pub-id-type="pmid">23382203</pub-id></mixed-citation></ref><ref id="DEV138248C3"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Alvarez-Buylla</surname><given-names>A.</given-names></name>, <name name-style="western"><surname>García-Verdugo</surname><given-names>J. M.</given-names></name> and <name name-style="western"><surname>Tramontin</surname><given-names>A. D.</given-names></name></person-group> (<year>2001</year>). <article-title>A unified hypothesis on the lineage of neural stem cells</article-title>. <source><italic>Nat. Rev. Neurosci.</italic></source><volume>2</volume>, <fpage>287</fpage>-<lpage>293</lpage>. <pub-id pub-id-type="doi">10.1038/35067582</pub-id><pub-id pub-id-type="pmid">11283751</pub-id></mixed-citation></ref><ref id="DEV138248C4"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Arai</surname><given-names>Y.</given-names></name>, <name name-style="western"><surname>Pulvers</surname><given-names>J. N.</given-names></name>, <name name-style="western"><surname>Haffner</surname><given-names>C.</given-names></name>, <name name-style="western"><surname>Schilling</surname><given-names>B.</given-names></name>, <name name-style="western"><surname>Nüsslein</surname><given-names>I.</given-names></name>, <name name-style="western"><surname>Calegari</surname><given-names>F.</given-names></name> and <name name-style="western"><surname>Huttner</surname><given-names>W. B.</given-names></name></person-group> (<year>2011</year>). <article-title>Neural stem and progenitor cells shorten S-phase on commitment to neuron production</article-title>. <source><italic>Nat. Commun.</italic></source><volume>2</volume>, <fpage>154</fpage><pub-id pub-id-type="doi">10.1038/ncomms1155</pub-id><pub-id pub-id-type="pmid">21224845</pub-id></mixed-citation></ref><ref id="DEV138248C5"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Arlotta</surname><given-names>P.</given-names></name>, <name name-style="western"><surname>Molyneaux</surname><given-names>B. J.</given-names></name>, <name name-style="western"><surname>Jabaudon</surname><given-names>D.</given-names></name>, <name name-style="western"><surname>Yoshida</surname><given-names>Y.</given-names></name> and <name name-style="western"><surname>Macklis</surname><given-names>J. D.</given-names></name></person-group> (<year>2008</year>). <article-title>Ctip2 controls the differentiation of medium spiny neurons and the establishment of the cellular architecture of the striatum</article-title>. <source><italic>J. Neurosci.</italic></source><volume>28</volume>, <fpage>622</fpage>-<lpage>632</lpage>. <pub-id pub-id-type="doi">10.1523/JNEUROSCI.2986-07.2008</pub-id><pub-id pub-id-type="pmid">18199763</pub-id></mixed-citation></ref><ref id="DEV138248C6"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Bohner</surname><given-names>A. P.</given-names></name>, <name name-style="western"><surname>Akers</surname><given-names>R. M.</given-names></name> and <name name-style="western"><surname>McConnell</surname><given-names>S. K.</given-names></name></person-group> (<year>1997</year>). <article-title>Induction of deep layer cortical neurons in vitro</article-title>. <source><italic>Development</italic></source><volume>124</volume>, <fpage>915</fpage>-<lpage>923</lpage>.<pub-id pub-id-type="pmid">9043072</pub-id></mixed-citation></ref><ref id="DEV138248C7"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Bosch</surname><given-names>M.</given-names></name>, <name name-style="western"><surname>Pineda</surname><given-names>J. R.</given-names></name>, <name name-style="western"><surname>Suñol</surname><given-names>C.</given-names></name>, <name name-style="western"><surname>Petriz</surname><given-names>J.</given-names></name>, <name name-style="western"><surname>Cattaneo</surname><given-names>E.</given-names></name>, <name name-style="western"><surname>Alberch</surname><given-names>J.</given-names></name> and <name name-style="western"><surname>Canals</surname><given-names>J. M.</given-names></name></person-group> (<year>2004</year>). <article-title>Induction of GABAergic phenotype in a neural stem cell line for transplantation in an excitotoxic model of Huntington's disease</article-title>. <source><italic>Exp. Neurol.</italic></source><volume>190</volume>, <fpage>42</fpage>-<lpage>58</lpage>. <pub-id pub-id-type="doi">10.1016/j.expneurol.2004.06.027</pub-id><pub-id pub-id-type="pmid">15473979</pub-id></mixed-citation></ref><ref id="DEV138248C8"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Brazel</surname><given-names>C. Y.</given-names></name>, <name name-style="western"><surname>Romanko</surname><given-names>M. J.</given-names></name>, <name name-style="western"><surname>Rothstein</surname><given-names>R. P.</given-names></name> and <name name-style="western"><surname>Levison</surname><given-names>S. W.</given-names></name></person-group> (<year>2003</year>). <article-title>Roles of the mammalian subventricular zone in brain development</article-title>. <source><italic>Prog. Neurobiol.</italic></source><volume>69</volume>, <fpage>49</fpage>-<lpage>69</lpage>. <pub-id pub-id-type="doi">10.1016/S0301-0082(03)00002-9</pub-id><pub-id pub-id-type="pmid">12637172</pub-id></mixed-citation></ref><ref id="DEV138248C9"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Burek</surname><given-names>M. J.</given-names></name> and <name name-style="western"><surname>Oppenheim</surname><given-names>R. W.</given-names></name></person-group> (<year>1996</year>). <article-title>Programmed cell death in the developing nervous system</article-title>. <source><italic>Brain Pathol.</italic></source><volume>6</volume>, <fpage>427</fpage>-<lpage>446</lpage>. <pub-id pub-id-type="doi">10.1111/j.1750-3639.1996.tb00874.x</pub-id><pub-id pub-id-type="pmid">8944315</pub-id></mixed-citation></ref><ref id="DEV138248C10"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Cai</surname><given-names>Q.</given-names></name>, <name name-style="western"><surname>Dierich</surname><given-names>A.</given-names></name>, <name name-style="western"><surname>Oulad-Abdelghani</surname><given-names>M.</given-names></name>, <name name-style="western"><surname>Chan</surname><given-names>S.</given-names></name> and <name name-style="western"><surname>Kastner</surname><given-names>P.</given-names></name></person-group> (<year>2009</year>). <article-title>Helios deficiency has minimal impact on T cell development and function</article-title>. <source><italic>J. Immunol.</italic></source><volume>183</volume>, <fpage>2303</fpage>-<lpage>2311</lpage>. <pub-id pub-id-type="doi">10.4049/jimmunol.0901407</pub-id><pub-id pub-id-type="pmid">19620299</pub-id></mixed-citation></ref><ref id="DEV138248C11"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Canals</surname><given-names>J. M.</given-names></name>, <name name-style="western"><surname>Pineda</surname><given-names>J. R.</given-names></name>, <name name-style="western"><surname>Torres-Peraza</surname><given-names>J. F.</given-names></name>, <name name-style="western"><surname>Bosch</surname><given-names>M.</given-names></name>, <name name-style="western"><surname>Martín-Ibañez</surname><given-names>R.</given-names></name>, <name name-style="western"><surname>Muñoz</surname><given-names>M. T.</given-names></name>, <name name-style="western"><surname>Mengod</surname><given-names>G.</given-names></name>, <name name-style="western"><surname>Ernfors</surname><given-names>P.</given-names></name> and <name name-style="western"><surname>Alberch</surname><given-names>J.</given-names></name></person-group> (<year>2004</year>). <article-title>Brain-derived neurotrophic factor regulates the onset and severity of motor dysfunction associated with enkephalinergic neuronal degeneration in Huntington's disease</article-title>. <source><italic>J. Neurosci.</italic></source><volume>24</volume>, <fpage>7727</fpage>-<lpage>7739</lpage>. <pub-id pub-id-type="doi">10.1523/JNEUROSCI.1197-04.2004</pub-id><pub-id pub-id-type="pmid">15342740</pub-id></mixed-citation></ref><ref id="DEV138248C12"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Cobb</surname><given-names>B. S.</given-names></name> and <name name-style="western"><surname>Smale</surname><given-names>S. T.</given-names></name></person-group> (<year>2005</year>). <article-title>Ikaros-family proteins: in search of molecular functions during lymphocyte development</article-title>. <source><italic>Curr. Top. Microbiol. Immunol.</italic></source><volume>290</volume>, <fpage>29</fpage>-<lpage>47</lpage>. <pub-id pub-id-type="doi">10.1007/3-540-26363-2_3</pub-id><pub-id pub-id-type="pmid">16480038</pub-id></mixed-citation></ref><ref id="DEV138248C13"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Dimou</surname><given-names>L.</given-names></name> and <name name-style="western"><surname>Götz</surname><given-names>M.</given-names></name></person-group> (<year>2014</year>). <article-title>Glial cells as progenitors and stem cells: new roles in the healthy and diseased brain</article-title>. <source><italic>Physiol. Rev.</italic></source><volume>94</volume>, <fpage>709</fpage>-<lpage>737</lpage>. <pub-id pub-id-type="doi">10.1152/physrev.00036.2013</pub-id><pub-id pub-id-type="pmid">24987003</pub-id></mixed-citation></ref><ref id="DEV138248C14"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Durieux</surname><given-names>P. F.</given-names></name>, <name name-style="western"><surname>Schiffmann</surname><given-names>S. N.</given-names></name> and <name name-style="western"><surname>de Kerchove d'Exaerde</surname><given-names>A.</given-names></name></person-group> (<year>2012</year>). <article-title>Differential regulation of motor control and response to dopaminergic drugs by D1R and D2R neurons in distinct dorsal striatum subregions</article-title>. <source><italic>EMBO J.</italic></source><volume>31</volume>, <fpage>640</fpage>-<lpage>653</lpage>. <pub-id pub-id-type="doi">10.1038/emboj.2011.400</pub-id><pub-id pub-id-type="pmid">22068054</pub-id></mixed-citation></ref><ref id="DEV138248C15"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Edlund</surname><given-names>T.</given-names></name> and <name name-style="western"><surname>Jessell</surname><given-names>T. M.</given-names></name></person-group> (<year>1999</year>). <article-title>Progression from extrinsic to intrinsic signaling in cell fate specification: a view from the nervous system</article-title>. <source><italic>Cell</italic></source><volume>96</volume>, <fpage>211</fpage>-<lpage>224</lpage>. <pub-id pub-id-type="doi">10.1016/S0092-8674(00)80561-9</pub-id><pub-id pub-id-type="pmid">9988216</pub-id></mixed-citation></ref><ref id="DEV138248C16"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Ehrman</surname><given-names>L. A.</given-names></name>, <name name-style="western"><surname>Mu</surname><given-names>X.</given-names></name>, <name name-style="western"><surname>Waclaw</surname><given-names>R. R.</given-names></name>, <name name-style="western"><surname>Yoshida</surname><given-names>Y.</given-names></name>, <name name-style="western"><surname>Vorhees</surname><given-names>C. V.</given-names></name>, <name name-style="western"><surname>Klein</surname><given-names>W. H.</given-names></name> and <name name-style="western"><surname>Campbell</surname><given-names>K.</given-names></name></person-group> (<year>2013</year>). <article-title>The LIM homeobox gene Isl1 is required for the correct development of the striatonigral pathway in the mouse</article-title>. <source><italic>Proc. Natl. Acad. Sci. USA</italic></source><volume>110</volume>, <fpage>E4026</fpage>-<lpage>E4035</lpage>. <pub-id pub-id-type="doi">10.1073/pnas.1308275110</pub-id><pub-id pub-id-type="pmid">24082127</pub-id></mixed-citation></ref><ref id="DEV138248C17"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Eisenstat</surname><given-names>D. D.</given-names></name>, <name name-style="western"><surname>Liu</surname><given-names>J. K.</given-names></name>, <name name-style="western"><surname>Mione</surname><given-names>M.</given-names></name>, <name name-style="western"><surname>Zhong</surname><given-names>W.</given-names></name>, <name name-style="western"><surname>Yu</surname><given-names>G.</given-names></name>, <name name-style="western"><surname>Anderson</surname><given-names>S. A.</given-names></name>, <name name-style="western"><surname>Ghattas</surname><given-names>I.</given-names></name>, <name name-style="western"><surname>Puelles</surname><given-names>L.</given-names></name> and <name name-style="western"><surname>Rubenstein</surname><given-names>J. L.</given-names></name></person-group> (<year>1999</year>). <article-title>DLX-1, DLX-2, and DLX-5 expression define distinct stages of basal forebrain differentiation</article-title>. <source><italic>J. Comp. Neurol.</italic></source><volume>414</volume>, <fpage>217</fpage>-<lpage>237</lpage>. <pub-id pub-id-type="doi">10.1002/(SICI)1096-9861(19991115)414:2<217::AID-CNE6>3.0.CO;2-I</pub-id><pub-id pub-id-type="pmid">10516593</pub-id></mixed-citation></ref><ref id="DEV138248C18"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Ericson</surname><given-names>J.</given-names></name>, <name name-style="western"><surname>Morton</surname><given-names>S.</given-names></name>, <name name-style="western"><surname>Kawakami</surname><given-names>A.</given-names></name>, <name name-style="western"><surname>Roelink</surname><given-names>H.</given-names></name> and <name name-style="western"><surname>Jessell</surname><given-names>T. M.</given-names></name></person-group> (<year>1996</year>). <article-title>Two critical periods of Sonic Hedgehog signaling required for the specification of motor neuron identity</article-title>. <source><italic>Cell</italic></source><volume>87</volume>, <fpage>661</fpage>-<lpage>673</lpage>. <pub-id pub-id-type="doi">10.1016/S0092-8674(00)81386-0</pub-id><pub-id pub-id-type="pmid">8929535</pub-id></mixed-citation></ref><ref id="DEV138248C19"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Flames</surname><given-names>N.</given-names></name>, <name name-style="western"><surname>Pla</surname><given-names>R.</given-names></name>, <name name-style="western"><surname>Gelman</surname><given-names>D. M.</given-names></name>, <name name-style="western"><surname>Rubenstein</surname><given-names>J. L. R.</given-names></name>, <name name-style="western"><surname>Puelles</surname><given-names>L.</given-names></name> and <name name-style="western"><surname>Marín</surname><given-names>O.</given-names></name></person-group> (<year>2007</year>). <article-title>Delineation of multiple subpallial progenitor domains by the combinatorial expression of transcriptional codes</article-title>. <source><italic>J. Neurosci.</italic></source><volume>27</volume>, <fpage>9682</fpage>-<lpage>9695</lpage>. <pub-id pub-id-type="doi">10.1523/JNEUROSCI.2750-07.2007</pub-id><pub-id pub-id-type="pmid">17804629</pub-id></mixed-citation></ref><ref id="DEV138248C20"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Garcia-Dominguez</surname><given-names>M.</given-names></name>, <name name-style="western"><surname>Poquet</surname><given-names>C.</given-names></name>, <name name-style="western"><surname>Garel</surname><given-names>S.</given-names></name> and <name name-style="western"><surname>Charnay</surname><given-names>P.</given-names></name></person-group> (<year>2003</year>). <article-title>Ebf gene function is required for coupling neuronal differentiation and cell cycle exit</article-title>. <source><italic>Development</italic></source><volume>130</volume>, <fpage>6013</fpage>-<lpage>6025</lpage>. <pub-id pub-id-type="doi">10.1242/dev.00840</pub-id><pub-id pub-id-type="pmid">14573522</pub-id></mixed-citation></ref><ref id="DEV138248C21"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Garel</surname><given-names>S.</given-names></name>, <name name-style="western"><surname>Marín</surname><given-names>F.</given-names></name>, <name name-style="western"><surname>Grosschedl</surname><given-names>R.</given-names></name> and <name name-style="western"><surname>Charnay</surname><given-names>P.</given-names></name></person-group> (<year>1999</year>). <article-title>Ebf1 controls early cell differentiation in the embryonic striatum</article-title>. <source><italic>Development</italic></source><volume>126</volume>, <fpage>5285</fpage>-<lpage>5294</lpage>.<pub-id pub-id-type="pmid">10556054</pub-id></mixed-citation></ref><ref id="DEV138248C22"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Georgopoulos</surname><given-names>K.</given-names></name></person-group> (<year>2002</year>). <article-title>Haematopoietic cell-fate decisions, chromatin regulation and ikaros</article-title>. <source><italic>Nat. Rev. Immunol.</italic></source><volume>2</volume>, <fpage>162</fpage>-<lpage>174</lpage>. <pub-id pub-id-type="doi">10.1038/nri747</pub-id><pub-id pub-id-type="pmid">11913067</pub-id></mixed-citation></ref><ref id="DEV138248C23"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Gerfen</surname><given-names>C. R.</given-names></name></person-group> (<year>1992</year>). <article-title>The neostriatal mosaic: multiple levels of compartmental organization</article-title>. <source><italic>Trends Neurosci.</italic></source><volume>15</volume>, <fpage>133</fpage>-<lpage>139</lpage>. <pub-id pub-id-type="doi">10.1016/0166-2236(92)90355-C</pub-id><pub-id pub-id-type="pmid">1374971</pub-id></mixed-citation></ref><ref id="DEV138248C24"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Gong</surname><given-names>S.</given-names></name>, <name name-style="western"><surname>Zheng</surname><given-names>C.</given-names></name>, <name name-style="western"><surname>Doughty</surname><given-names>M. L.</given-names></name>, <name name-style="western"><surname>Losos</surname><given-names>K.</given-names></name>, <name name-style="western"><surname>Didkovsky</surname><given-names>N.</given-names></name>, <name name-style="western"><surname>Schambra</surname><given-names>U. B.</given-names></name>, <name name-style="western"><surname>Nowak</surname><given-names>N. J.</given-names></name>, <name name-style="western"><surname>Joyner</surname><given-names>A.</given-names></name>, <name name-style="western"><surname>Leblanc</surname><given-names>G.</given-names></name>, <name name-style="western"><surname>Hatten</surname><given-names>M. E.</given-names></name><etal>et al.</etal></person-group> (<year>2003</year>). <article-title>A gene expression atlas of the central nervous system based on bacterial artificial chromosomes</article-title>. <source><italic>Nature</italic></source><volume>425</volume>, <fpage>917</fpage>-<lpage>925</lpage>. <pub-id pub-id-type="doi">10.1038/nature02033</pub-id><pub-id pub-id-type="pmid">14586460</pub-id></mixed-citation></ref><ref id="DEV138248C25"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Götz</surname><given-names>M.</given-names></name> and <name name-style="western"><surname>Barde</surname><given-names>Y.-A.</given-names></name></person-group> (<year>2005</year>). <article-title>Radial glial cells defined and major intermediates between embryonic stem cells and CNS neurons</article-title>. <source><italic>Neuron</italic></source><volume>46</volume>, <fpage>369</fpage>-<lpage>372</lpage>. <pub-id pub-id-type="doi">10.1016/j.neuron.2005.04.012</pub-id><pub-id pub-id-type="pmid">15882633</pub-id></mixed-citation></ref><ref id="DEV138248C26"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Gould</surname><given-names>E.</given-names></name>, <name name-style="western"><surname>Reeves</surname><given-names>A. J.</given-names></name>, <name name-style="western"><surname>Graziano</surname><given-names>M. S.</given-names></name> and <name name-style="western"><surname>Gross</surname><given-names>C. G.</given-names></name></person-group> (<year>1999</year>). <article-title>Neurogenesis in the neocortex of adult primates</article-title>. <source><italic>Science</italic></source><volume>286</volume>, <fpage>548</fpage>-<lpage>552</lpage>. <pub-id pub-id-type="doi">10.1126/science.286.5439.548</pub-id><pub-id pub-id-type="pmid">10521353</pub-id></mixed-citation></ref><ref id="DEV138248C27"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Graybiel</surname><given-names>A. M.</given-names></name></person-group> (<year>2008</year>). <article-title>Habits, rituals, and the evaluative brain</article-title>. <source><italic>Annu. Rev. Neurosci.</italic></source><volume>31</volume>, <fpage>359</fpage>-<lpage>387</lpage>. <pub-id pub-id-type="doi">10.1146/annurev.neuro.29.051605.112851</pub-id><pub-id pub-id-type="pmid">18558860</pub-id></mixed-citation></ref><ref id="DEV138248C28"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Hahm</surname><given-names>K.</given-names></name>, <name name-style="western"><surname>Cobb</surname><given-names>B. S.</given-names></name>, <name name-style="western"><surname>McCarty</surname><given-names>A. S.</given-names></name>, <name name-style="western"><surname>Brown</surname><given-names>K. E.</given-names></name>, <name name-style="western"><surname>Klug</surname><given-names>C. A.</given-names></name>, <name name-style="western"><surname>Lee</surname><given-names>R.</given-names></name>, <name name-style="western"><surname>Akashi</surname><given-names>K.</given-names></name>, <name name-style="western"><surname>Weissman</surname><given-names>I. L.</given-names></name>, <name name-style="western"><surname>Fisher</surname><given-names>A. G.</given-names></name> and <name name-style="western"><surname>Smale</surname><given-names>S. T.</given-names></name></person-group> (<year>1998</year>). <article-title>Helios, a T cell-restricted Ikaros family member that quantitatively associates with Ikaros at centromeric heterochromatin</article-title>. <source><italic>Genes Dev.</italic></source><volume>12</volume>, <fpage>782</fpage>-<lpage>796</lpage>. <pub-id pub-id-type="doi">10.1101/gad.12.6.782</pub-id><pub-id pub-id-type="pmid">9512513</pub-id></mixed-citation></ref><ref id="DEV138248C29"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Harbour</surname><given-names>J. W.</given-names></name></person-group> (<year>2000</year>). <article-title>The Rb/E2F pathway: expanding roles and emerging paradigms</article-title>. <source><italic>Genes Dev.</italic></source><volume>14</volume>, <fpage>2393</fpage>-<lpage>2409</lpage>. <pub-id pub-id-type="doi">10.1101/gad.813200</pub-id><pub-id pub-id-type="pmid">11018009</pub-id></mixed-citation></ref><ref id="DEV138248C30"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Hardwick</surname><given-names>L. J. A.</given-names></name> and <name name-style="western"><surname>Philpott</surname><given-names>A.</given-names></name></person-group> (<year>2014</year>). <article-title>Nervous decision-making: to divide or differentiate</article-title>. <source><italic>Trends Genet.</italic></source><volume>30</volume>, <fpage>254</fpage>-<lpage>261</lpage>. <pub-id pub-id-type="doi">10.1016/j.tig.2014.04.001</pub-id><pub-id pub-id-type="pmid">24791612</pub-id></mixed-citation></ref><ref id="DEV138248C31"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>John</surname><given-names>L. B.</given-names></name>, <name name-style="western"><surname>Yoong</surname><given-names>S.</given-names></name> and <name name-style="western"><surname>Ward</surname><given-names>A. C.</given-names></name></person-group> (<year>2009</year>). <article-title>Evolution of the Ikaros gene family: implications for the origins of adaptive immunity</article-title>. <source><italic>J. Immunol.</italic></source><volume>182</volume>, <fpage>4792</fpage>-<lpage>4799</lpage>. <pub-id pub-id-type="doi">10.4049/jimmunol.0802372</pub-id><pub-id pub-id-type="pmid">19342657</pub-id></mixed-citation></ref><ref id="DEV138248C32"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Jueptner</surname><given-names>M.</given-names></name> and <name name-style="western"><surname>Weiller</surname><given-names>C.</given-names></name></person-group> (<year>1998</year>). <article-title>A review of differences between basal ganglia and cerebellar control of movements as revealed by functional imaging studies</article-title>. <source><italic>Brain</italic></source><volume>121</volume>, <fpage>1437</fpage>-<lpage>1449</lpage>. <pub-id pub-id-type="doi">10.1093/brain/121.8.1437</pub-id><pub-id pub-id-type="pmid">9712006</pub-id></mixed-citation></ref><ref id="DEV138248C33"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Kanthan</surname><given-names>R.</given-names></name>, <name name-style="western"><surname>Fried</surname><given-names>I.</given-names></name>, <name name-style="western"><surname>Rueckl</surname><given-names>T.</given-names></name>, <name name-style="western"><surname>Senger</surname><given-names>J.-L.</given-names></name> and <name name-style="western"><surname>Kanthan</surname><given-names>S. C.</given-names></name></person-group> (<year>2010</year>). <article-title>Expression of cell cycle proteins in male breast carcinoma</article-title>. <source><italic>World J. Surg. Oncol.</italic></source><volume>8</volume>, <fpage>10</fpage><pub-id pub-id-type="doi">10.1186/1477-7819-8-10</pub-id><pub-id pub-id-type="pmid">20152033</pub-id></mixed-citation></ref><ref id="DEV138248C34"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Kim</surname><given-names>H.-J.</given-names></name>, <name name-style="western"><surname>Hida</surname><given-names>H.</given-names></name>, <name name-style="western"><surname>Jung</surname><given-names>C.-G.</given-names></name>, <name name-style="western"><surname>Miura</surname><given-names>Y.</given-names></name> and <name name-style="western"><surname>Nishino</surname><given-names>H.</given-names></name></person-group> (<year>2006</year>). <article-title>Treatment with deferoxamine increases neurons from neural stem/progenitor cells</article-title>. <source><italic>Brain Res.</italic></source><volume>1092</volume>, <fpage>1</fpage>-<lpage>15</lpage>. <pub-id pub-id-type="doi">10.1016/j.brainres.2006.02.046</pub-id><pub-id pub-id-type="pmid">16697980</pub-id></mixed-citation></ref><ref id="DEV138248C35"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Kim</surname><given-names>H.-J.</given-names></name>, <name name-style="western"><surname>Barnitz</surname><given-names>R. A.</given-names></name>, <name name-style="western"><surname>Kreslavsky</surname><given-names>T.</given-names></name>, <name name-style="western"><surname>Brown</surname><given-names>F. D.</given-names></name>, <name name-style="western"><surname>Moffett</surname><given-names>H.</given-names></name>, <name name-style="western"><surname>Lemieux</surname><given-names>M. E.</given-names></name>, <name name-style="western"><surname>Kaygusuz</surname><given-names>Y.</given-names></name>, <name name-style="western"><surname>Meissner</surname><given-names>T.</given-names></name>, <name name-style="western"><surname>Holderried</surname><given-names>T. A. W.</given-names></name>, <name name-style="western"><surname>Chan</surname><given-names>S.</given-names></name><etal>et al.</etal></person-group> (<year>2015</year>). <article-title>Stable inhibitory activity of regulatory T cells requires the transcription factor Helios</article-title>. <source><italic>Science</italic></source><volume>350</volume>, <fpage>334</fpage>-<lpage>339</lpage>. <pub-id pub-id-type="doi">10.1126/science.aad0616</pub-id><pub-id pub-id-type="pmid">26472910</pub-id></mixed-citation></ref><ref id="DEV138248C36"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Kreitzer</surname><given-names>A. C.</given-names></name></person-group> (<year>2009</year>). <article-title>Physiology and pharmacology of striatal neurons</article-title>. <source><italic>Annu. Rev. Neurosci.</italic></source><volume>32</volume>, <fpage>127</fpage>-<lpage>147</lpage>. <pub-id pub-id-type="doi">10.1146/annurev.neuro.051508.135422</pub-id><pub-id pub-id-type="pmid">19400717</pub-id></mixed-citation></ref><ref id="DEV138248C37"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Kristiansen</surname><given-names>M.</given-names></name> and <name name-style="western"><surname>Ham</surname><given-names>J.</given-names></name></person-group> (<year>2014</year>). <article-title>Programmed cell death during neuronal development: the sympathetic neuron model</article-title>. <source><italic>Cell Death Differ.</italic></source><volume>21</volume>, <fpage>1025</fpage>-<lpage>1035</lpage>. <pub-id pub-id-type="doi">10.1038/cdd.2014.47</pub-id><pub-id pub-id-type="pmid">24769728</pub-id></mixed-citation></ref><ref id="DEV138248C38"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Lacomme</surname><given-names>M.</given-names></name>, <name name-style="western"><surname>Liaubet</surname><given-names>L.</given-names></name>, <name name-style="western"><surname>Pituello</surname><given-names>F.</given-names></name> and <name name-style="western"><surname>Bel-Vialar</surname><given-names>S.</given-names></name></person-group> (<year>2012</year>). <article-title>NEUROG2 drives cell cycle exit of neuronal precursors by specifically repressing a subset of cyclins acting at the G1 and S phases of the cell cycle</article-title>. <source><italic>Mol. Cell. Biol.</italic></source><volume>32</volume>, <fpage>2596</fpage>-<lpage>2607</lpage>. <pub-id pub-id-type="doi">10.1128/MCB.06745-11</pub-id><pub-id pub-id-type="pmid">22547683</pub-id></mixed-citation></ref><ref id="DEV138248C39"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Lange</surname><given-names>C.</given-names></name>, <name name-style="western"><surname>Huttner</surname><given-names>W. B.</given-names></name> and <name name-style="western"><surname>Calegari</surname><given-names>F.</given-names></name></person-group> (<year>2009</year>). <article-title>Cdk4/cyclinD1 overexpression in neural stem cells shortens G1, delays neurogenesis, and promotes the generation and expansion of basal progenitors</article-title>. <source><italic>Cell Stem Cell</italic></source><volume>5</volume>, <fpage>320</fpage>-<lpage>331</lpage>. <pub-id pub-id-type="doi">10.1016/j.stem.2009.05.026</pub-id><pub-id pub-id-type="pmid">19733543</pub-id></mixed-citation></ref><ref id="DEV138248C40"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Leng</surname><given-names>X.</given-names></name>, <name name-style="western"><surname>Connell-Crowley</surname><given-names>L.</given-names></name>, <name name-style="western"><surname>Goodrich</surname><given-names>D.</given-names></name> and <name name-style="western"><surname>Harper</surname><given-names>J. W.</given-names></name></person-group> (<year>1997</year>). <article-title>S-phase entry upon ectopic expression of G1 cyclin-dependent kinases in the absence of retinoblastoma protein phosphorylation</article-title>. <source><italic>Curr. Biol.</italic></source><volume>7</volume>, <fpage>709</fpage>-<lpage>712</lpage>. <pub-id pub-id-type="doi">10.1016/S0960-9822(06)00301-0</pub-id><pub-id pub-id-type="pmid">9285720</pub-id></mixed-citation></ref><ref id="DEV138248C41"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Lobo</surname><given-names>M. K.</given-names></name>, <name name-style="western"><surname>Karsten</surname><given-names>S. L.</given-names></name>, <name name-style="western"><surname>Gray</surname><given-names>M.</given-names></name>, <name name-style="western"><surname>Geschwind</surname><given-names>D. H.</given-names></name> and <name name-style="western"><surname>Yang</surname><given-names>X. W.</given-names></name></person-group> (<year>2006</year>). <article-title>FACS-array profiling of striatal projection neuron subtypes in juvenile and adult mouse brains</article-title>. <source><italic>Nat. Neurosci.</italic></source><volume>9</volume>, <fpage>443</fpage>-<lpage>452</lpage>. <pub-id pub-id-type="doi">10.1038/nn1654</pub-id><pub-id pub-id-type="pmid">16491081</pub-id></mixed-citation></ref><ref id="DEV138248C42"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Lobo</surname><given-names>M. K.</given-names></name>, <name name-style="western"><surname>Yeh</surname><given-names>C.</given-names></name> and <name name-style="western"><surname>Yang</surname><given-names>X. W.</given-names></name></person-group> (<year>2008</year>). <article-title>Pivotal role of early B-cell factor 1 in development of striatonigral medium spiny neurons in the matrix compartment</article-title>. <source><italic>J. Neurosci. Res.</italic></source><volume>86</volume>, <fpage>2134</fpage>-<lpage>2146</lpage>. <pub-id pub-id-type="doi">10.1002/jnr.21666</pub-id><pub-id pub-id-type="pmid">18338816</pub-id></mixed-citation></ref><ref id="DEV138248C43"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Lopez</surname><given-names>F.</given-names></name>, <name name-style="western"><surname>Belloc</surname><given-names>F.</given-names></name>, <name name-style="western"><surname>Lacombe</surname><given-names>F.</given-names></name>, <name name-style="western"><surname>Dumain</surname><given-names>P.</given-names></name>, <name name-style="western"><surname>Reiffers</surname><given-names>J.</given-names></name>, <name name-style="western"><surname>Bernard</surname><given-names>P.</given-names></name> and <name name-style="western"><surname>Boisseau</surname><given-names>M. R.</given-names></name></person-group> (<year>1991</year>). <article-title>Modalities of synthesis of Ki67 antigen during the stimulation of lymphocytes</article-title>. <source><italic>Cytometry</italic></source><volume>12</volume>, <fpage>42</fpage>-<lpage>49</lpage>. <pub-id pub-id-type="doi">10.1002/cyto.990120107</pub-id><pub-id pub-id-type="pmid">1999122</pub-id></mixed-citation></ref><ref id="DEV138248C44"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Lu</surname><given-names>K.-M.</given-names></name>, <name name-style="western"><surname>Evans</surname><given-names>S. M.</given-names></name>, <name name-style="western"><surname>Hirano</surname><given-names>S.</given-names></name> and <name name-style="western"><surname>Liu</surname><given-names>F.-C.</given-names></name></person-group> (<year>2014</year>). <article-title>Dual role for Islet-1 in promoting striatonigral and repressing striatopallidal genetic programs to specify striatonigral cell identity</article-title>. <source><italic>Proc. Natl. Acad. Sci. USA</italic></source><volume>111</volume>, <fpage>E168</fpage>-<lpage>E177</lpage>. <pub-id pub-id-type="doi">10.1073/pnas.1319138111</pub-id><pub-id pub-id-type="pmid">24351932</pub-id></mixed-citation></ref><ref id="DEV138248C45"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Luft</surname><given-names>A. R.</given-names></name> and <name name-style="western"><surname>Buitrago</surname><given-names>M. M.</given-names></name></person-group> (<year>2005</year>). <article-title>Stages of motor skill learning</article-title>. <source><italic>Mol. Neurobiol.</italic></source><volume>32</volume>, <fpage>205</fpage>-<lpage>216</lpage>. <pub-id pub-id-type="doi">10.1385/MN:32:3:205</pub-id><pub-id pub-id-type="pmid">16385137</pub-id></mixed-citation></ref><ref id="DEV138248C46"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Lukas</surname><given-names>J.</given-names></name>, <name name-style="western"><surname>Herzinger</surname><given-names>T.</given-names></name>, <name name-style="western"><surname>Hansen</surname><given-names>K.</given-names></name>, <name name-style="western"><surname>Moroni</surname><given-names>M. C.</given-names></name>, <name name-style="western"><surname>Resnitzky</surname><given-names>D.</given-names></name>, <name name-style="western"><surname>Helin</surname><given-names>K.</given-names></name>, <name name-style="western"><surname>Reed</surname><given-names>S. I.</given-names></name> and <name name-style="western"><surname>Bartek</surname><given-names>J.</given-names></name></person-group> (<year>1997</year>). <article-title>Cyclin E-induced S phase without activation of the pRb/E2F pathway</article-title>. <source><italic>Genes Dev.</italic></source><volume>11</volume>, <fpage>1479</fpage>-<lpage>1492</lpage>. <pub-id pub-id-type="doi">10.1101/gad.11.11.1479</pub-id><pub-id pub-id-type="pmid">9192874</pub-id></mixed-citation></ref><ref id="DEV138248C47"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Martín-Ibáñez</surname><given-names>R.</given-names></name>, <name name-style="western"><surname>Crespo</surname><given-names>E.</given-names></name>, <name name-style="western"><surname>Urbán</surname><given-names>N.</given-names></name>, <name name-style="western"><surname>Sergent-Tanguy</surname><given-names>S.</given-names></name>, <name name-style="western"><surname>Herranz</surname><given-names>C.</given-names></name>, <name name-style="western"><surname>Jaumot</surname><given-names>M.</given-names></name>, <name name-style="western"><surname>Valiente</surname><given-names>M.</given-names></name>, <name name-style="western"><surname>Long</surname><given-names>J. E.</given-names></name>, <name name-style="western"><surname>Pineda</surname><given-names>J. R.</given-names></name>, <name name-style="western"><surname>Andreu</surname><given-names>C.</given-names></name><etal>et al.</etal></person-group> (<year>2010</year>). <article-title>Ikaros-1 couples cell cycle arrest of late striatal precursors with neurogenesis of enkephalinergic neurons</article-title>. <source><italic>J. Comp. Neurol.</italic></source><volume>518</volume>, <fpage>329</fpage>-<lpage>351</lpage>. <pub-id pub-id-type="doi">10.1002/cne.22215</pub-id><pub-id pub-id-type="pmid">19950118</pub-id></mixed-citation></ref><ref id="DEV138248C48"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Martín-Ibáñez</surname><given-names>R.</given-names></name>, <name name-style="western"><surname>Crespo</surname><given-names>E.</given-names></name>, <name name-style="western"><surname>Esgleas</surname><given-names>M.</given-names></name>, <name name-style="western"><surname>Urban</surname><given-names>N.</given-names></name>, <name name-style="western"><surname>Wang</surname><given-names>B.</given-names></name>, <name name-style="western"><surname>Waclaw</surname><given-names>R.</given-names></name>, <name name-style="western"><surname>Georgopoulos</surname><given-names>K.</given-names></name>, <name name-style="western"><surname>Martínez</surname><given-names>S.</given-names></name>, <name name-style="western"><surname>Campbell</surname><given-names>K.</given-names></name>, <name name-style="western"><surname>Vicario-Abejón</surname><given-names>C.</given-names></name><etal>et al.</etal></person-group> (<year>2012</year>). <article-title>Helios transcription factor expression depends on Gsx2 and Dlx1&2 function in developing striatal matrix neurons</article-title>. <source><italic>Stem Cells Dev.</italic></source><volume>21</volume>, <fpage>2239</fpage>-<lpage>2251</lpage>. <pub-id pub-id-type="doi">10.1089/scd.2011.0607</pub-id><pub-id pub-id-type="pmid">22142223</pub-id></mixed-citation></ref><ref id="DEV138248C49"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Mason</surname><given-names>H. A.</given-names></name>, <name name-style="western"><surname>Rakowiecki</surname><given-names>S. M.</given-names></name>, <name name-style="western"><surname>Raftopoulou</surname><given-names>M.</given-names></name>, <name name-style="western"><surname>Nery</surname><given-names>S.</given-names></name>, <name name-style="western"><surname>Huang</surname><given-names>Y.</given-names></name>, <name name-style="western"><surname>Gridley</surname><given-names>T.</given-names></name> and <name name-style="western"><surname>Fishell</surname><given-names>G.</given-names></name></person-group> (<year>2005</year>). <article-title>Notch signaling coordinates the patterning of striatal compartments</article-title>. <source><italic>Development</italic></source><volume>132</volume>, <fpage>4247</fpage>-<lpage>4258</lpage>. <pub-id pub-id-type="doi">10.1242/dev.02008</pub-id><pub-id pub-id-type="pmid">16120638</pub-id></mixed-citation></ref><ref id="DEV138248C50"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>McConnell</surname><given-names>S. K.</given-names></name> and <name name-style="western"><surname>Kaznowski</surname><given-names>C. E.</given-names></name></person-group> (<year>1991</year>). <article-title>Cell cycle dependence of laminar determination in developing neocortex</article-title>. <source><italic>Science</italic></source><volume>254</volume>, <fpage>282</fpage>-<lpage>285</lpage>. <pub-id pub-id-type="doi">10.1126/science.1925583</pub-id><pub-id pub-id-type="pmid">1925583</pub-id></mixed-citation></ref><ref id="DEV138248C51"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Merkle</surname><given-names>F. T.</given-names></name> and <name name-style="western"><surname>Alvarez-Buylla</surname><given-names>A.</given-names></name></person-group> (<year>2006</year>). <article-title>Neural stem cells in mammalian development</article-title>. <source><italic>Curr. Opin. Cell Biol.</italic></source><volume>18</volume>, <fpage>704</fpage>-<lpage>709</lpage>. <pub-id pub-id-type="doi">10.1016/j.ceb.2006.09.008</pub-id><pub-id pub-id-type="pmid">17046226</pub-id></mixed-citation></ref><ref id="DEV138248C52"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Mérot</surname><given-names>Y.</given-names></name>, <name name-style="western"><surname>Rétaux</surname><given-names>S.</given-names></name> and <name name-style="western"><surname>Heng</surname><given-names>J. I.-T.</given-names></name></person-group> (<year>2009</year>). <article-title>Molecular mechanisms of projection neuron production and maturation in the developing cerebral cortex</article-title>. <source><italic>Semin. Cell Dev. Biol.</italic></source><volume>20</volume>, <fpage>726</fpage>-<lpage>734</lpage>. <pub-id pub-id-type="doi">10.1016/j.semcdb.2009.04.003</pub-id><pub-id pub-id-type="pmid">19442543</pub-id></mixed-citation></ref><ref id="DEV138248C53"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Misumi</surname><given-names>S.</given-names></name>, <name name-style="western"><surname>Kim</surname><given-names>T.-S.</given-names></name>, <name name-style="western"><surname>Jung</surname><given-names>C.-G.</given-names></name>, <name name-style="western"><surname>Masuda</surname><given-names>T.</given-names></name>, <name name-style="western"><surname>Urakawa</surname><given-names>S.</given-names></name>, <name name-style="western"><surname>Isobe</surname><given-names>Y.</given-names></name>, <name name-style="western"><surname>Furuyama</surname><given-names>F.</given-names></name>, <name name-style="western"><surname>Nishino</surname><given-names>H.</given-names></name> and <name name-style="western"><surname>Hida</surname><given-names>H.</given-names></name></person-group> (<year>2008</year>). <article-title>Enhanced neurogenesis from neural progenitor cells with G1/S-phase cell cycle arrest is mediated by transforming growth factor beta1</article-title>. <source><italic>Eur. J. Neurosci.</italic></source><volume>28</volume>, <fpage>1049</fpage>-<lpage>1059</lpage>. <pub-id pub-id-type="doi">10.1111/j.1460-9568.2008.06420.x</pub-id><pub-id pub-id-type="pmid">18783370</pub-id></mixed-citation></ref><ref id="DEV138248C54"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Miyachi</surname><given-names>S.</given-names></name>, <name name-style="western"><surname>Hikosaka</surname><given-names>O.</given-names></name> and <name name-style="western"><surname>Lu</surname><given-names>X.</given-names></name></person-group> (<year>2002</year>). <article-title>Differential activation of monkey striatal neurons in the early and late stages of procedural learning</article-title>. <source><italic>Exp. Brain Res.</italic></source><volume>146</volume>, <fpage>122</fpage>-<lpage>126</lpage>. <pub-id pub-id-type="doi">10.1007/s00221-002-1213-7</pub-id><pub-id pub-id-type="pmid">12192586</pub-id></mixed-citation></ref><ref id="DEV138248C55"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Ninkovic</surname><given-names>J.</given-names></name> and <name name-style="western"><surname>Götz</surname><given-names>M.</given-names></name></person-group> (<year>2013</year>). <article-title>Fate specification in the adult brain – lessons for eliciting neurogenesis from glial cells</article-title>. <source><italic>BioEssays</italic></source><volume>35</volume>, <fpage>242</fpage>-<lpage>252</lpage>. <pub-id pub-id-type="doi">10.1002/bies.201200108</pub-id><pub-id pub-id-type="pmid">23335359</pub-id></mixed-citation></ref><ref id="DEV138248C56"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Ohtani</surname><given-names>K.</given-names></name>, <name name-style="western"><surname>DeGregori</surname><given-names>J.</given-names></name> and <name name-style="western"><surname>Nevins</surname><given-names>J. R.</given-names></name></person-group> (<year>1995</year>). <article-title>Regulation of the cyclin E gene by transcription factor E2F1</article-title>. <source><italic>Proc. Natl. Acad. Sci. USA</italic></source><volume>92</volume>, <fpage>12146</fpage>-<lpage>12150</lpage>. <pub-id pub-id-type="doi">10.1073/pnas.92.26.12146</pub-id><pub-id pub-id-type="pmid">8618861</pub-id></mixed-citation></ref><ref id="DEV138248C57"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Ohtsubo</surname><given-names>M.</given-names></name> and <name name-style="western"><surname>Roberts</surname><given-names>J. M.</given-names></name></person-group> (<year>1993</year>). <article-title>Cyclin-dependent regulation of G1 in mammalian fibroblasts</article-title>. <source><italic>Science</italic></source><volume>259</volume>, <fpage>1908</fpage>-<lpage>1912</lpage>. <pub-id pub-id-type="doi">10.1126/science.8384376</pub-id><pub-id pub-id-type="pmid">8384376</pub-id></mixed-citation></ref><ref id="DEV138248C58"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Ohtsubo</surname><given-names>M.</given-names></name>, <name name-style="western"><surname>Theodoras</surname><given-names>A. M.</given-names></name>, <name name-style="western"><surname>Schumacher</surname><given-names>J.</given-names></name>, <name name-style="western"><surname>Roberts</surname><given-names>J. M.</given-names></name> and <name name-style="western"><surname>Pagano</surname><given-names>M.</given-names></name></person-group> (<year>1995</year>). <article-title>Human cyclin E, a nuclear protein essential for the G1-to-S phase transition</article-title>. <source><italic>Mol. Cell. Biol.</italic></source><volume>15</volume>, <fpage>2612</fpage>-<lpage>2624</lpage>. <pub-id pub-id-type="doi">10.1128/MCB.15.5.2612</pub-id><pub-id pub-id-type="pmid">7739542</pub-id></mixed-citation></ref><ref id="DEV138248C59"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Okabe</surname><given-names>M.</given-names></name>, <name name-style="western"><surname>Ikawa</surname><given-names>M.</given-names></name>, <name name-style="western"><surname>Kominami</surname><given-names>K.</given-names></name>, <name name-style="western"><surname>Nakanishi</surname><given-names>T.</given-names></name> and <name name-style="western"><surname>Nishimune</surname><given-names>Y.</given-names></name></person-group> (<year>1997</year>). <article-title>‘Green mice’ as a source of ubiquitous green cells</article-title>. <source><italic>FEBS Lett.</italic></source><volume>407</volume>, <fpage>313</fpage>-<lpage>319</lpage>. <pub-id pub-id-type="doi">10.1016/S0014-5793(97)00313-X</pub-id><pub-id pub-id-type="pmid">9175875</pub-id></mixed-citation></ref><ref id="DEV138248C60"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Pilaz</surname><given-names>L.-J.</given-names></name>, <name name-style="western"><surname>Patti</surname><given-names>D.</given-names></name>, <name name-style="western"><surname>Marcy</surname><given-names>G.</given-names></name>, <name name-style="western"><surname>Ollier</surname><given-names>E.</given-names></name>, <name name-style="western"><surname>Pfister</surname><given-names>S.</given-names></name>, <name name-style="western"><surname>Douglas</surname><given-names>R. J.</given-names></name>, <name name-style="western"><surname>Betizeau</surname><given-names>M.</given-names></name>, <name name-style="western"><surname>Gautier</surname><given-names>E.</given-names></name>, <name name-style="western"><surname>Cortay</surname><given-names>V.</given-names></name>, <name name-style="western"><surname>Doerflinger</surname><given-names>N.</given-names></name><etal>et al.</etal></person-group> (<year>2009</year>). <article-title>Forced G1-phase reduction alters mode of division, neuron number, and laminar phenotype in the cerebral cortex</article-title>. <source><italic>Proc. Natl. Acad. Sci. USA</italic></source><volume>106</volume>, <fpage>21924</fpage>-<lpage>21929</lpage>. <pub-id pub-id-type="doi">10.1073/pnas.0909894106</pub-id><pub-id pub-id-type="pmid">19959663</pub-id></mixed-citation></ref><ref id="DEV138248C61"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Pilz</surname><given-names>G.-A.</given-names></name>, <name name-style="western"><surname>Shitamukai</surname><given-names>A.</given-names></name>, <name name-style="western"><surname>Reillo</surname><given-names>I.</given-names></name>, <name name-style="western"><surname>Pacary</surname><given-names>E.</given-names></name>, <name name-style="western"><surname>Schwausch</surname><given-names>J.</given-names></name>, <name name-style="western"><surname>Stahl</surname><given-names>R.</given-names></name>, <name name-style="western"><surname>Ninkovic</surname><given-names>J.</given-names></name>, <name name-style="western"><surname>Snippert</surname><given-names>H. J.</given-names></name>, <name name-style="western"><surname>Clevers</surname><given-names>H.</given-names></name>, <name name-style="western"><surname>Godinho</surname><given-names>L.</given-names></name><etal>et al.</etal></person-group> (<year>2013</year>). <article-title>Amplification of progenitors in the mammalian telencephalon includes a new radial glial cell type</article-title>. <source><italic>Nat. Commun.</italic></source><volume>4</volume>, <fpage>2125</fpage><pub-id pub-id-type="doi">10.1038/ncomms3125</pub-id><pub-id pub-id-type="pmid">23839311</pub-id></mixed-citation></ref><ref id="DEV138248C62"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Rallu</surname><given-names>M.</given-names></name>, <name name-style="western"><surname>Corbin</surname><given-names>J. G.</given-names></name> and <name name-style="western"><surname>Fishell</surname><given-names>G.</given-names></name></person-group> (<year>2002</year>). <article-title>Parsing the prosencephalon</article-title>. <source><italic>Nat. Rev. Neurosci.</italic></source><volume>3</volume>, <fpage>943</fpage>-<lpage>951</lpage>. <pub-id pub-id-type="doi">10.1038/nrn989</pub-id><pub-id pub-id-type="pmid">12461551</pub-id></mixed-citation></ref><ref id="DEV138248C63"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Rebollo</surname><given-names>A.</given-names></name> and <name name-style="western"><surname>Schmitt</surname><given-names>C.</given-names></name></person-group> (<year>2003</year>). <article-title>Ikaros, Aiolos and Helios: transcription regulators and lymphoid malignancies</article-title>. <source><italic>Immunol. Cell Biol.</italic></source><volume>81</volume>, <fpage>171</fpage>-<lpage>175</lpage>. <pub-id pub-id-type="doi">10.1046/j.1440-1711.2003.01159.x</pub-id><pub-id pub-id-type="pmid">12752680</pub-id></mixed-citation></ref><ref id="DEV138248C64"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Resnitzky</surname><given-names>D.</given-names></name>, <name name-style="western"><surname>Gossen</surname><given-names>M.</given-names></name>, <name name-style="western"><surname>Bujard</surname><given-names>H.</given-names></name> and <name name-style="western"><surname>Reed</surname><given-names>S. I.</given-names></name></person-group> (<year>1994</year>). <article-title>Acceleration of the G1/S phase transition by expression of cyclins D1 and E with an inducible system</article-title>. <source><italic>Mol. Cell. Biol.</italic></source><volume>14</volume>, <fpage>1669</fpage>-<lpage>1679</lpage>. <pub-id pub-id-type="doi">10.1128/MCB.14.3.1669</pub-id><pub-id pub-id-type="pmid">8114703</pub-id></mixed-citation></ref><ref id="DEV138248C65"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Sausbier</surname><given-names>M.</given-names></name>, <name name-style="western"><surname>Hu</surname><given-names>H.</given-names></name>, <name name-style="western"><surname>Arntz</surname><given-names>C.</given-names></name>, <name name-style="western"><surname>Feil</surname><given-names>S.</given-names></name>, <name name-style="western"><surname>Kamm</surname><given-names>S.</given-names></name>, <name name-style="western"><surname>Adelsberger</surname><given-names>H.</given-names></name>, <name name-style="western"><surname>Sausbier</surname><given-names>U.</given-names></name>, <name name-style="western"><surname>Sailer</surname><given-names>C. A.</given-names></name>, <name name-style="western"><surname>Feil</surname><given-names>R.</given-names></name>, <name name-style="western"><surname>Hofmann</surname><given-names>F.</given-names></name><etal>et al.</etal></person-group> (<year>2004</year>). <article-title>Cerebellar ataxia and Purkinje cell dysfunction caused by Ca2<sup>+</sup>-activated K<sup>+</sup> channel deficiency</article-title>. <source><italic>Proc. Natl. Acad. Sci. USA</italic></source><volume>101</volume>, <fpage>9474</fpage>-<lpage>9478</lpage>. <pub-id pub-id-type="doi">10.1073/pnas.0401702101</pub-id><pub-id pub-id-type="pmid">15194823</pub-id></mixed-citation></ref><ref id="DEV138248C66"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Scholzen</surname><given-names>T.</given-names></name> and <name name-style="western"><surname>Gerdes</surname><given-names>J.</given-names></name></person-group> (<year>2000</year>). <article-title>The Ki-67 protein: from the known and the unknown</article-title>. <source><italic>J. Cell. Physiol.</italic></source><volume>182</volume>, <fpage>311</fpage>-<lpage>322</lpage>. <pub-id pub-id-type="doi">10.1002/(SICI)1097-4652(200003)182:3<311::AID-JCP1>3.0.CO;2-9</pub-id><pub-id pub-id-type="pmid">10653597</pub-id></mixed-citation></ref><ref id="DEV138248C67"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Stroobants</surname><given-names>S.</given-names></name>, <name name-style="western"><surname>Gantois</surname><given-names>I.</given-names></name>, <name name-style="western"><surname>Pooters</surname><given-names>T.</given-names></name> and <name name-style="western"><surname>D'Hooge</surname><given-names>R.</given-names></name></person-group> (<year>2013</year>). <article-title>Increased gait variability in mice with small cerebellar cortex lesions and normal rotarod performance</article-title>. <source><italic>Behav. Brain Res.</italic></source><volume>241</volume>, <fpage>32</fpage>-<lpage>37</lpage>. <pub-id pub-id-type="doi">10.1016/j.bbr.2012.11.034</pub-id><pub-id pub-id-type="pmid">23219967</pub-id></mixed-citation></ref><ref id="DEV138248C68"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Takahashi</surname><given-names>T.</given-names></name>, <name name-style="western"><surname>Nowakowski</surname><given-names>R. S.</given-names></name> and <name name-style="western"><surname>Caviness</surname><given-names>V. S.</given-names></name></person-group> (<year>1992</year>). <article-title>BUdR as an S-phase marker for quantitative studies of cytokinetic behaviour in the murine cerebral ventricular zone</article-title>. <source><italic>J. Neurocytol.</italic></source><volume>21</volume>, <fpage>185</fpage>-<lpage>197</lpage>. <pub-id pub-id-type="doi">10.1007/BF01194977</pub-id><pub-id pub-id-type="pmid">1373183</pub-id></mixed-citation></ref><ref id="DEV138248C69"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Takahashi</surname><given-names>T.</given-names></name>, <name name-style="western"><surname>Nowakowski</surname><given-names>R. S.</given-names></name> and <name name-style="western"><surname>Caviness</surname><given-names>V. S.</given-names></name></person-group> (<year>1995</year>). <article-title>The cell cycle of the pseudostratified ventricular epithelium of the embryonic murine cerebral wall</article-title>. <source><italic>J. Neurosci.</italic></source><volume>15</volume>, <fpage>6046</fpage>-<lpage>6057</lpage>.<pub-id pub-id-type="pmid">7666188</pub-id></mixed-citation></ref><ref id="DEV138248C70"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Tanabe</surname><given-names>Y.</given-names></name>, <name name-style="western"><surname>William</surname><given-names>C.</given-names></name> and <name name-style="western"><surname>Jessell</surname><given-names>T. M.</given-names></name></person-group> (<year>1998</year>). <article-title>Specification of motor neuron identity by the MNR2 homeodomain protein</article-title>. <source><italic>Cell</italic></source><volume>95</volume>, <fpage>67</fpage>-<lpage>80</lpage>. <pub-id pub-id-type="doi">10.1016/S0092-8674(00)81783-3</pub-id><pub-id pub-id-type="pmid">9778248</pub-id></mixed-citation></ref><ref id="DEV138248C71"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Turrero García</surname><given-names>M.</given-names></name>, <name name-style="western"><surname>Chang</surname><given-names>Y.</given-names></name>, <name name-style="western"><surname>Arai</surname><given-names>Y.</given-names></name> and <name name-style="western"><surname>Huttner</surname><given-names>W. B.</given-names></name></person-group> (<year>2015</year>). <article-title>S-phase duration is the main target of cell cycle regulation in neural progenitors of developing ferret neocortex</article-title>. <source><italic>J. Comp. Neurol.</italic></source><volume>524</volume>, <fpage>456</fpage>-<lpage>470</lpage>. <pub-id pub-id-type="doi">10.1002/cne.23801</pub-id><pub-id pub-id-type="pmid">25963823</pub-id></mixed-citation></ref><ref id="DEV138248C72"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Urbán</surname><given-names>N.</given-names></name>, <name name-style="western"><surname>Martín-Ibáñez</surname><given-names>R.</given-names></name>, <name name-style="western"><surname>Herranz</surname><given-names>C.</given-names></name>, <name name-style="western"><surname>Esgleas</surname><given-names>M.</given-names></name>, <name name-style="western"><surname>Crespo</surname><given-names>E.</given-names></name>, <name name-style="western"><surname>Pardo</surname><given-names>M.</given-names></name>, <name name-style="western"><surname>Crespo-Enríquez</surname><given-names>I.</given-names></name>, <name name-style="western"><surname>Méndez-Gómez</surname><given-names>H. R.</given-names></name>, <name name-style="western"><surname>Waclaw</surname><given-names>R.</given-names></name>, <name name-style="western"><surname>Chatzi</surname><given-names>C.</given-names></name><etal>et al.</etal></person-group> (<year>2010</year>). <article-title>Nolz1 promotes striatal neurogenesis through the regulation of retinoic acid signaling</article-title>. <source><italic>Neural Dev.</italic></source><volume>5</volume>, <fpage>21</fpage><pub-id pub-id-type="doi">10.1186/1749-8104-5-21</pub-id><pub-id pub-id-type="pmid">20735826</pub-id></mixed-citation></ref><ref id="DEV138248C73"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Vinueza Veloz</surname><given-names>M. F.</given-names></name>, <name name-style="western"><surname>Buijsen</surname><given-names>R. A. M.</given-names></name>, <name name-style="western"><surname>Willemsen</surname><given-names>R.</given-names></name>, <name name-style="western"><surname>Cupido</surname><given-names>A.</given-names></name>, <name name-style="western"><surname>Bosman</surname><given-names>L. W. J.</given-names></name>, <name name-style="western"><surname>Koekkoek</surname><given-names>S. K. E.</given-names></name>, <name name-style="western"><surname>Potters</surname><given-names>J. W.</given-names></name>, <name name-style="western"><surname>Oostra</surname><given-names>B. A.</given-names></name> and <name name-style="western"><surname>De Zeeuw</surname><given-names>C. I.</given-names></name></person-group> (<year>2012</year>). <article-title>The effect of an mGluR5 inhibitor on procedural memory and avoidance discrimination impairments in Fmr1 KO mice</article-title>. <source><italic>Genes. Brain. Behav.</italic></source><volume>11</volume>, <fpage>325</fpage>-<lpage>331</lpage>. <pub-id pub-id-type="doi">10.1111/j.1601-183X.2011.00763.x</pub-id><pub-id pub-id-type="pmid">22257369</pub-id></mixed-citation></ref><ref id="DEV138248C74"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Voorn</surname><given-names>P.</given-names></name>, <name name-style="western"><surname>Vanderschuren</surname><given-names>L. J. M. J.</given-names></name>, <name name-style="western"><surname>Groenewegen</surname><given-names>H. J.</given-names></name>, <name name-style="western"><surname>Robbins</surname><given-names>T. W.</given-names></name> and <name name-style="western"><surname>Pennartz</surname><given-names>C. M. A.</given-names></name></person-group> (<year>2004</year>). <article-title>Putting a spin on the dorsal-ventral divide of the striatum</article-title>. <source><italic>Trends Neurosci.</italic></source><volume>27</volume>, <fpage>468</fpage>-<lpage>474</lpage>. <pub-id pub-id-type="doi">10.1016/j.tins.2004.06.006</pub-id><pub-id pub-id-type="pmid">15271494</pub-id></mixed-citation></ref><ref id="DEV138248C75"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Waclaw</surname><given-names>R. R.</given-names></name>, <name name-style="western"><surname>Wang</surname><given-names>B.</given-names></name>, <name name-style="western"><surname>Pei</surname><given-names>Z.</given-names></name>, <name name-style="western"><surname>Ehrman</surname><given-names>L. A.</given-names></name> and <name name-style="western"><surname>Campbell</surname><given-names>K.</given-names></name></person-group> (<year>2009</year>). <article-title>Distinct temporal requirements for the homeobox gene Gsx2 in specifying striatal and olfactory bulb neuronal fates</article-title>. <source><italic>Neuron</italic></source><volume>63</volume>, <fpage>451</fpage>-<lpage>465</lpage>. <pub-id pub-id-type="doi">10.1016/j.neuron.2009.07.015</pub-id><pub-id pub-id-type="pmid">19709628</pub-id></mixed-citation></ref><ref id="DEV138248C76"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Yin</surname><given-names>H. H.</given-names></name> and <name name-style="western"><surname>Knowlton</surname><given-names>B. J.</given-names></name></person-group> (<year>2006</year>). <article-title>The role of the basal ganglia in habit formation</article-title>. <source><italic>Nat. Rev. Neurosci.</italic></source><volume>7</volume>, <fpage>464</fpage>-<lpage>476</lpage>. <pub-id pub-id-type="doi">10.1038/nrn1919</pub-id><pub-id pub-id-type="pmid">16715055</pub-id></mixed-citation></ref><ref id="DEV138248C77"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Yin</surname><given-names>H. H.</given-names></name>, <name name-style="western"><surname>Knowlton</surname><given-names>B. J.</given-names></name> and <name name-style="western"><surname>Balleine</surname><given-names>B. W.</given-names></name></person-group> (<year>2004</year>). <article-title>Lesions of dorsolateral striatum preserve outcome expectancy but disrupt habit formation in instrumental learning</article-title>. <source><italic>Eur. J. Neurosci.</italic></source><volume>19</volume>, <fpage>181</fpage>-<lpage>189</lpage>. <pub-id pub-id-type="doi">10.1111/j.1460-9568.2004.03095.x</pub-id><pub-id pub-id-type="pmid">14750976</pub-id></mixed-citation></ref><ref id="DEV138248C78"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Yoshida</surname><given-names>T.</given-names></name> and <name name-style="western"><surname>Georgopoulos</surname><given-names>K.</given-names></name></person-group> (<year>2014</year>). <article-title>Ikaros fingers on lymphocyte differentiation</article-title>. <source><italic>Int. J. Hematol.</italic></source><volume>100</volume>, <fpage>220</fpage>-<lpage>229</lpage>. <pub-id pub-id-type="doi">10.1007/s12185-014-1644-5</pub-id><pub-id pub-id-type="pmid">25085254</pub-id></mixed-citation></ref><ref id="DEV138248C79"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Yun</surname><given-names>K.</given-names></name>, <name name-style="western"><surname>Fischman</surname><given-names>S.</given-names></name>, <name name-style="western"><surname>Johnson</surname><given-names>J.</given-names></name>, <name name-style="western"><surname>Hrabe de Angelis</surname><given-names>M.</given-names></name>, <name name-style="western"><surname>Weinmaster</surname><given-names>G.</given-names></name> and <name name-style="western"><surname>Rubenstein</surname><given-names>J. L. R.</given-names></name></person-group> (<year>2002</year>). <article-title>Modulation of the notch signaling by Mash1 and Dlx1/2 regulates sequential specification and differentiation of progenitor cell types in the subcortical telencephalon</article-title>. <source><italic>Development</italic></source><volume>129</volume>, <fpage>5029</fpage>-<lpage>5040</lpage>.<pub-id pub-id-type="pmid">12397111</pub-id></mixed-citation></ref><ref id="DEV138248C80"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Zhang</surname><given-names>Z.</given-names></name>, <name name-style="western"><surname>Swindle</surname><given-names>C. S.</given-names></name>, <name name-style="western"><surname>Bates</surname><given-names>J. T.</given-names></name>, <name name-style="western"><surname>Ko</surname><given-names>R.</given-names></name>, <name name-style="western"><surname>Cotta</surname><given-names>C. V.</given-names></name> and <name name-style="western"><surname>Klug</surname><given-names>C. A.</given-names></name></person-group> (<year>2007</year>). <article-title>Expression of a non-DNA-binding isoform of Helios induces T-cell lymphoma in mice</article-title>. <source><italic>Blood</italic></source><volume>109</volume>, <fpage>2190</fpage>-<lpage>2197</lpage>. <pub-id pub-id-type="doi">10.1182/blood-2005-01-031930</pub-id><pub-id pub-id-type="pmid">17110463</pub-id></mixed-citation></ref></ref-list></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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