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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Fat4-Dchs1 signalling controls cell proliferation in developing vertebrae</title><author><name sortKey="Kuta, Anna" sort="Kuta, Anna" uniqKey="Kuta A" first="Anna" last="Kuta">Anna Kuta</name><affiliation><nlm:aff id="af1"><addr-line>Department of Craniofacial Development and Stem Cell Biology</addr-line>,<institution>King's College London, Dental Institute</institution>,<addr-line>Guy's Tower, Floor 27, London SE1 9RT</addr-line>,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Mao, Yaopan" sort="Mao, Yaopan" uniqKey="Mao Y" first="Yaopan" last="Mao">Yaopan Mao</name><affiliation><nlm:aff id="af2"><institution>Howard Hughes Medical Institute, Waksman Institute and</institution><addr-line>Department of Molecular Biology and Biochemistry</addr-line>,<institution>Rutgers, The State University of New Jersey</institution>,<addr-line>Piscataway, NJ 08854</addr-line>,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Martin, Tina" sort="Martin, Tina" uniqKey="Martin T" first="Tina" last="Martin">Tina Martin</name><affiliation><nlm:aff id="af1"><addr-line>Department of Craniofacial Development and Stem Cell Biology</addr-line>,<institution>King's College London, Dental Institute</institution>,<addr-line>Guy's Tower, Floor 27, London SE1 9RT</addr-line>,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Ferreira De Sousa, Catia" sort="Ferreira De Sousa, Catia" uniqKey="Ferreira De Sousa C" first="Catia" last="Ferreira De Sousa">Catia Ferreira De Sousa</name><affiliation><nlm:aff id="af1"><addr-line>Department of Craniofacial Development and Stem Cell Biology</addr-line>,<institution>King's College London, Dental Institute</institution>,<addr-line>Guy's Tower, Floor 27, London SE1 9RT</addr-line>,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Whiting, Danielle" sort="Whiting, Danielle" uniqKey="Whiting D" first="Danielle" last="Whiting">Danielle Whiting</name><affiliation><nlm:aff id="af1"><addr-line>Department of Craniofacial Development and Stem Cell Biology</addr-line>,<institution>King's College London, Dental Institute</institution>,<addr-line>Guy's Tower, Floor 27, London SE1 9RT</addr-line>,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Zakaria, Sana" sort="Zakaria, Sana" uniqKey="Zakaria S" first="Sana" last="Zakaria">Sana Zakaria</name><affiliation><nlm:aff id="af1"><addr-line>Department of Craniofacial Development and Stem Cell Biology</addr-line>,<institution>King's College London, Dental Institute</institution>,<addr-line>Guy's Tower, Floor 27, London SE1 9RT</addr-line>,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Crespo Enriquez, Ivan" sort="Crespo Enriquez, Ivan" uniqKey="Crespo Enriquez I" first="Ivan" last="Crespo-Enriquez">Ivan Crespo-Enriquez</name><affiliation><nlm:aff id="af1"><addr-line>Department of Craniofacial Development and Stem Cell Biology</addr-line>,<institution>King's College London, Dental Institute</institution>,<addr-line>Guy's Tower, Floor 27, London SE1 9RT</addr-line>,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Evans, Philippa" sort="Evans, Philippa" uniqKey="Evans P" first="Philippa" last="Evans">Philippa Evans</name><affiliation><nlm:aff id="af1"><addr-line>Department of Craniofacial Development and Stem Cell Biology</addr-line>,<institution>King's College London, Dental Institute</institution>,<addr-line>Guy's Tower, Floor 27, London SE1 9RT</addr-line>,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Balczerski, Bartosz" sort="Balczerski, Bartosz" uniqKey="Balczerski B" first="Bartosz" last="Balczerski">Bartosz Balczerski</name><affiliation><nlm:aff id="af1"><addr-line>Department of Craniofacial Development and Stem Cell Biology</addr-line>,<institution>King's College London, Dental Institute</institution>,<addr-line>Guy's Tower, Floor 27, London SE1 9RT</addr-line>,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Mankoo, Baljinder" sort="Mankoo, Baljinder" uniqKey="Mankoo B" first="Baljinder" last="Mankoo">Baljinder Mankoo</name><affiliation><nlm:aff id="af3"><addr-line>Randall Division of Cell and Molecular Biophysics, Faculty of Life Sciences & Medicine</addr-line>,<institution>King's College London</institution>,<addr-line>Guy's Campus, London SE1 1UL</addr-line>,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Irvine, Kenneth D" sort="Irvine, Kenneth D" uniqKey="Irvine K" first="Kenneth D." last="Irvine">Kenneth D. Irvine</name><affiliation><nlm:aff id="af2"><institution>Howard Hughes Medical Institute, Waksman Institute and</institution><addr-line>Department of Molecular Biology and Biochemistry</addr-line>,<institution>Rutgers, The State University of New Jersey</institution>,<addr-line>Piscataway, NJ 08854</addr-line>,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Francis West, Philippa H" sort="Francis West, Philippa H" uniqKey="Francis West P" first="Philippa H." last="Francis-West">Philippa H. Francis-West</name><affiliation><nlm:aff id="af1"><addr-line>Department of Craniofacial Development and Stem Cell Biology</addr-line>,<institution>King's College London, Dental Institute</institution>,<addr-line>Guy's Tower, Floor 27, London SE1 9RT</addr-line>,<country>UK</country></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27381226</idno><idno type="pmc">4958319</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4958319</idno><idno type="RBID">PMC:4958319</idno><idno type="doi">10.1242/dev.131037</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">000651</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000651</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Fat4-Dchs1 signalling controls cell proliferation in developing vertebrae</title><author><name sortKey="Kuta, Anna" sort="Kuta, Anna" uniqKey="Kuta A" first="Anna" last="Kuta">Anna Kuta</name><affiliation><nlm:aff id="af1"><addr-line>Department of Craniofacial Development and Stem Cell Biology</addr-line>,<institution>King's College London, Dental Institute</institution>,<addr-line>Guy's Tower, Floor 27, London SE1 9RT</addr-line>,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Mao, Yaopan" sort="Mao, Yaopan" uniqKey="Mao Y" first="Yaopan" last="Mao">Yaopan Mao</name><affiliation><nlm:aff id="af2"><institution>Howard Hughes Medical Institute, Waksman Institute and</institution><addr-line>Department of Molecular Biology and Biochemistry</addr-line>,<institution>Rutgers, The State University of New Jersey</institution>,<addr-line>Piscataway, NJ 08854</addr-line>,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Martin, Tina" sort="Martin, Tina" uniqKey="Martin T" first="Tina" last="Martin">Tina Martin</name><affiliation><nlm:aff id="af1"><addr-line>Department of Craniofacial Development and Stem Cell Biology</addr-line>,<institution>King's College London, Dental Institute</institution>,<addr-line>Guy's Tower, Floor 27, London SE1 9RT</addr-line>,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Ferreira De Sousa, Catia" sort="Ferreira De Sousa, Catia" uniqKey="Ferreira De Sousa C" first="Catia" last="Ferreira De Sousa">Catia Ferreira De Sousa</name><affiliation><nlm:aff id="af1"><addr-line>Department of Craniofacial Development and Stem Cell Biology</addr-line>,<institution>King's College London, Dental Institute</institution>,<addr-line>Guy's Tower, Floor 27, London SE1 9RT</addr-line>,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Whiting, Danielle" sort="Whiting, Danielle" uniqKey="Whiting D" first="Danielle" last="Whiting">Danielle Whiting</name><affiliation><nlm:aff id="af1"><addr-line>Department of Craniofacial Development and Stem Cell Biology</addr-line>,<institution>King's College London, Dental Institute</institution>,<addr-line>Guy's Tower, Floor 27, London SE1 9RT</addr-line>,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Zakaria, Sana" sort="Zakaria, Sana" uniqKey="Zakaria S" first="Sana" last="Zakaria">Sana Zakaria</name><affiliation><nlm:aff id="af1"><addr-line>Department of Craniofacial Development and Stem Cell Biology</addr-line>,<institution>King's College London, Dental Institute</institution>,<addr-line>Guy's Tower, Floor 27, London SE1 9RT</addr-line>,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Crespo Enriquez, Ivan" sort="Crespo Enriquez, Ivan" uniqKey="Crespo Enriquez I" first="Ivan" last="Crespo-Enriquez">Ivan Crespo-Enriquez</name><affiliation><nlm:aff id="af1"><addr-line>Department of Craniofacial Development and Stem Cell Biology</addr-line>,<institution>King's College London, Dental Institute</institution>,<addr-line>Guy's Tower, Floor 27, London SE1 9RT</addr-line>,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Evans, Philippa" sort="Evans, Philippa" uniqKey="Evans P" first="Philippa" last="Evans">Philippa Evans</name><affiliation><nlm:aff id="af1"><addr-line>Department of Craniofacial Development and Stem Cell Biology</addr-line>,<institution>King's College London, Dental Institute</institution>,<addr-line>Guy's Tower, Floor 27, London SE1 9RT</addr-line>,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Balczerski, Bartosz" sort="Balczerski, Bartosz" uniqKey="Balczerski B" first="Bartosz" last="Balczerski">Bartosz Balczerski</name><affiliation><nlm:aff id="af1"><addr-line>Department of Craniofacial Development and Stem Cell Biology</addr-line>,<institution>King's College London, Dental Institute</institution>,<addr-line>Guy's Tower, Floor 27, London SE1 9RT</addr-line>,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Mankoo, Baljinder" sort="Mankoo, Baljinder" uniqKey="Mankoo B" first="Baljinder" last="Mankoo">Baljinder Mankoo</name><affiliation><nlm:aff id="af3"><addr-line>Randall Division of Cell and Molecular Biophysics, Faculty of Life Sciences & Medicine</addr-line>,<institution>King's College London</institution>,<addr-line>Guy's Campus, London SE1 1UL</addr-line>,<country>UK</country></nlm:aff></affiliation></author><author><name sortKey="Irvine, Kenneth D" sort="Irvine, Kenneth D" uniqKey="Irvine K" first="Kenneth D." last="Irvine">Kenneth D. Irvine</name><affiliation><nlm:aff id="af2"><institution>Howard Hughes Medical Institute, Waksman Institute and</institution><addr-line>Department of Molecular Biology and Biochemistry</addr-line>,<institution>Rutgers, The State University of New Jersey</institution>,<addr-line>Piscataway, NJ 08854</addr-line>,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Francis West, Philippa H" sort="Francis West, Philippa H" uniqKey="Francis West P" first="Philippa H." last="Francis-West">Philippa H. Francis-West</name><affiliation><nlm:aff id="af1"><addr-line>Department of Craniofacial Development and Stem Cell Biology</addr-line>,<institution>King's College London, Dental Institute</institution>,<addr-line>Guy's Tower, Floor 27, London SE1 9RT</addr-line>,<country>UK</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="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The protocadherins Fat4 and Dchs1 act as a receptor-ligand pair to regulate many developmental processes in mice and humans, including development of the vertebrae. Based on conservation of function between <italic>Drosophila</italic> and mammals, Fat4-Dchs1 signalling has been proposed to regulate planar cell polarity (PCP) and activity of the Hippo effectors Yap and Taz, which regulate cell proliferation, survival and differentiation. There is strong evidence for Fat regulation of PCP in mammals but the link with the Hippo pathway is unclear. In <italic>Fat4<sup>−/−</sup></italic> and <italic>Dchs1<sup>−/−</sup></italic> mice, many vertebrae are split along the midline and fused across the anterior-posterior axis, suggesting that these defects might arise due to altered cell polarity and/or changes in cell proliferation/differentiation. We show that the somite and sclerotome are specified appropriately, the transcriptional network that drives early chondrogenesis is intact, and that cell polarity within the sclerotome is unperturbed. We find that the key defect in <italic>Fat4</italic> and <italic>Dchs1</italic> mutant mice is decreased proliferation in the early sclerotome. This results in fewer chondrogenic cells within the developing vertebral body, which fail to condense appropriately along the midline. Analysis of <italic>Fat4;Yap</italic> and <italic>Fat4;Taz</italic> double mutants, and expression of their transcriptional target Ctgf, indicates that Fat4-Dchs1 regulates vertebral development independently of Yap and Taz. Thus, we have identified a new pathway crucial for the development of the vertebrae and our data indicate that novel mechanisms of Fat4-Dchs1 signalling have evolved to control cell proliferation within the developing vertebrae.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<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">27381226</article-id><article-id pub-id-type="pmc">4958319</article-id><article-id pub-id-type="doi">10.1242/dev.131037</article-id><article-id pub-id-type="publisher-id">DEV131037</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>Fat4-Dchs1 signalling controls cell proliferation in developing vertebrae</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Kuta</surname><given-names>Anna</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="author-notes" rid="AN1">*</xref></contrib><contrib contrib-type="author"><name><surname>Mao</surname><given-names>Yaopan</given-names></name><xref ref-type="aff" rid="af2">2</xref><xref ref-type="author-notes" rid="AN1">*</xref></contrib><contrib contrib-type="author"><name><surname>Martin</surname><given-names>Tina</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Ferreira de Sousa</surname><given-names>Catia</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Whiting</surname><given-names>Danielle</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Zakaria</surname><given-names>Sana</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Crespo-Enriquez</surname><given-names>Ivan</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Evans</surname><given-names>Philippa</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Balczerski</surname><given-names>Bartosz</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Mankoo</surname><given-names>Baljinder</given-names></name><xref ref-type="aff" rid="af3">3</xref></contrib><contrib contrib-type="author"><name><surname>Irvine</surname><given-names>Kenneth D.</given-names></name><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="false">http://orcid.org/0000-0001-5179-5892</contrib-id><name><surname>Francis-West</surname><given-names>Philippa H.</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="author-notes" rid="AN1">*</xref><xref ref-type="corresp" rid="cor1">‡</xref></contrib></contrib-group><aff id="af1"><label>1</label><addr-line>Department of Craniofacial Development and Stem Cell Biology</addr-line>,<institution>King's College London, Dental Institute</institution>,<addr-line>Guy's Tower, Floor 27, London SE1 9RT</addr-line>,<country>UK</country></aff><aff id="af2"><label>2</label><institution>Howard Hughes Medical Institute, Waksman Institute and</institution><addr-line>Department of Molecular Biology and Biochemistry</addr-line>,<institution>Rutgers, The State University of New Jersey</institution>,<addr-line>Piscataway, NJ 08854</addr-line>,<country>USA</country></aff><aff id="af3"><label>3</label><addr-line>Randall Division of Cell and Molecular Biophysics, Faculty of Life Sciences & Medicine</addr-line>,<institution>King's College London</institution>,<addr-line>Guy's Campus, London SE1 1UL</addr-line>,<country>UK</country></aff><author-notes><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>philippa.francis-west@kcl.ac.uk</email>)</corresp></author-notes><pub-date pub-type="ppub"><day>1</day><month>7</month><year>2016</year></pub-date><pub-date pub-type="pmc-release"><day>1</day><month>1</month><year>2017</year></pub-date><pmc-comment> PMC Release delay is 6 months and
0 days and was based on the
<volume>143</volume><issue>13</issue><fpage>2367</fpage><lpage>2375</lpage><history><date date-type="received"><day>16</day><month>9</month><year>2015</year></date><date date-type="accepted"><day>11</day><month>5</month><year>2016</year></date></history><permissions><copyright-statement>© 2016. Published by The Company of Biologists Ltd</copyright-statement><copyright-year>2016</copyright-year></permissions><self-uri content-type="pdf" xlink:href="develop-143-131037.pdf"></self-uri><abstract><p>The protocadherins Fat4 and Dchs1 act as a receptor-ligand pair to regulate many developmental processes in mice and humans, including development of the vertebrae. Based on conservation of function between <italic>Drosophila</italic> and mammals, Fat4-Dchs1 signalling has been proposed to regulate planar cell polarity (PCP) and activity of the Hippo effectors Yap and Taz, which regulate cell proliferation, survival and differentiation. There is strong evidence for Fat regulation of PCP in mammals but the link with the Hippo pathway is unclear. In <italic>Fat4<sup>−/−</sup></italic> and <italic>Dchs1<sup>−/−</sup></italic> mice, many vertebrae are split along the midline and fused across the anterior-posterior axis, suggesting that these defects might arise due to altered cell polarity and/or changes in cell proliferation/differentiation. We show that the somite and sclerotome are specified appropriately, the transcriptional network that drives early chondrogenesis is intact, and that cell polarity within the sclerotome is unperturbed. We find that the key defect in <italic>Fat4</italic> and <italic>Dchs1</italic> mutant mice is decreased proliferation in the early sclerotome. This results in fewer chondrogenic cells within the developing vertebral body, which fail to condense appropriately along the midline. Analysis of <italic>Fat4;Yap</italic> and <italic>Fat4;Taz</italic> double mutants, and expression of their transcriptional target Ctgf, indicates that Fat4-Dchs1 regulates vertebral development independently of Yap and Taz. Thus, we have identified a new pathway crucial for the development of the vertebrae and our data indicate that novel mechanisms of Fat4-Dchs1 signalling have evolved to control cell proliferation within the developing vertebrae.</p></abstract><abstract abstract-type="precis"><p><bold>Summary:</bold> The protocadherins Fat4 and Dchs1 promote proliferation in the developing mouse somites, independently of both the planar cell polarity pathway and the Yap/Taz Hippo effectors.</p></abstract><kwd-group><title>KEY WORDS</title><kwd>Fat4</kwd><kwd>Dchs1</kwd><kwd>Vertebrae</kwd><kwd>Somite</kwd><kwd>Chondrocyte</kwd><kwd>Yap1</kwd><kwd>Taz (Wwtr1)</kwd><kwd>Mouse</kwd></kwd-group><funding-group specific-use="FundRef"><award-group><funding-source><institution-wrap><institution>Biotechnology and Biological Sciences Research Council</institution><institution-id>http://dx.doi.org/10.13039/501100000268</institution-id></institution-wrap></funding-source><award-id>BB/G021074/1</award-id><award-id>BB/K001671/1</award-id><award-id>BB/K008668/1</award-id></award-group></funding-group><funding-group specific-use="FundRef"><award-group><funding-source><institution-wrap><institution>King's College London</institution><institution-id>http://dx.doi.org/10.13039/501100000764</institution-id></institution-wrap></funding-source></award-group></funding-group><funding-group specific-use="FundRef"><award-group><funding-source><institution-wrap><institution>Howard Hughes Medical Institute</institution><institution-id>http://dx.doi.org/10.13039/100000011</institution-id></institution-wrap></funding-source></award-group></funding-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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