Attenuated sensing of SHH by Ptch1 underlies evolution of bovine limbs.
Identifieur interne : 003607 ( PubMed/Corpus ); précédent : 003606; suivant : 003608Attenuated sensing of SHH by Ptch1 underlies evolution of bovine limbs.
Auteurs : Javier Lopez-Rios ; Amandine Duchesne ; Dario Speziale ; Guillaume Andrey ; Kevin A. Peterson ; Philipp Germann ; Erkan Unal ; Jing Liu ; Sandrine Floriot ; Sarah Barbey ; Yves Gallard ; Magdalena Müller-Gerbl ; Andrew D. Courtney ; Christophe Klopp ; Sabrina Rodriguez ; Robert Ivanek ; Christian Beisel ; Carol Wicking ; Dagmar Iber ; Benoit Robert ; Andrew P. Mcmahon ; Denis Duboule ; Rolf ZellerSource :
- Nature [ 1476-4687 ] ; 2014.
English descriptors
- KwdEn :
- Animals, Biological Evolution, Body Patterning, Cattle, Extremities (anatomy & histology), Extremities (embryology), Female, Gene Expression Regulation, Developmental (genetics), Hedgehog Proteins (metabolism), Limb Buds (anatomy & histology), Limb Buds (embryology), Male, Mesoderm (metabolism), Mice, Mice, Transgenic, Patched Receptors, Patched-1 Receptor, Receptors, Cell Surface (genetics), Receptors, Cell Surface (metabolism), Regulatory Sequences, Nucleic Acid (genetics).
- MESH :
- chemical , genetics : Receptors, Cell Surface.
- chemical , metabolism : Hedgehog Proteins, Receptors, Cell Surface.
- anatomy & histology : Extremities, Limb Buds.
- embryology : Extremities, Limb Buds.
- genetics : Gene Expression Regulation, Developmental, Regulatory Sequences, Nucleic Acid.
- metabolism : Mesoderm.
- Animals, Biological Evolution, Body Patterning, Cattle, Female, Male, Mice, Mice, Transgenic, Patched Receptors, Patched-1 Receptor.
Abstract
The large spectrum of limb morphologies reflects the wide evolutionary diversification of the basic pentadactyl pattern in tetrapods. In even-toed ungulates (artiodactyls, including cattle), limbs are adapted for running as a consequence of progressive reduction of their distal skeleton to symmetrical and elongated middle digits with hoofed phalanges. Here we analyse bovine embryos to establish that polarized gene expression is progressively lost during limb development in comparison to the mouse. Notably, the transcriptional upregulation of the Ptch1 gene, which encodes a Sonic hedgehog (SHH) receptor, is disrupted specifically in the bovine limb bud mesenchyme. This is due to evolutionary alteration of a Ptch1 cis-regulatory module, which no longer responds to graded SHH signalling during bovine handplate development. Our study provides a molecular explanation for the loss of digit asymmetry in bovine limb buds and suggests that modifications affecting the Ptch1 cis-regulatory landscape have contributed to evolutionary diversification of artiodactyl limbs.
DOI: 10.1038/nature13289
PubMed: 24990743
Links to Exploration step
pubmed:24990743Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Attenuated sensing of SHH by Ptch1 underlies evolution of bovine limbs.</title><author><name sortKey="Lopez Rios, Javier" sort="Lopez Rios, Javier" uniqKey="Lopez Rios J" first="Javier" last="Lopez-Rios">Javier Lopez-Rios</name><affiliation><nlm:affiliation>1] Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland [2].</nlm:affiliation></affiliation></author><author><name sortKey="Duchesne, Amandine" sort="Duchesne, Amandine" uniqKey="Duchesne A" first="Amandine" last="Duchesne">Amandine Duchesne</name><affiliation><nlm:affiliation>1] Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland [2] Institut National de la Recherche Agronomique, Génétique Animale et Biologie Intégrative, F-78350 Jouy-en-Josas, France [3].</nlm:affiliation></affiliation></author><author><name sortKey="Speziale, Dario" sort="Speziale, Dario" uniqKey="Speziale D" first="Dario" last="Speziale">Dario Speziale</name><affiliation><nlm:affiliation>Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland.</nlm:affiliation></affiliation></author><author><name sortKey="Andrey, Guillaume" sort="Andrey, Guillaume" uniqKey="Andrey G" first="Guillaume" last="Andrey">Guillaume Andrey</name><affiliation><nlm:affiliation>School of Life Sciences, Federal Institute of Technology Lausanne, CH-1015 Lausanne, Switzerland.</nlm:affiliation></affiliation></author><author><name sortKey="Peterson, Kevin A" sort="Peterson, Kevin A" uniqKey="Peterson K" first="Kevin A" last="Peterson">Kevin A. Peterson</name><affiliation><nlm:affiliation>Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Germann, Philipp" sort="Germann, Philipp" uniqKey="Germann P" first="Philipp" last="Germann">Philipp Germann</name><affiliation><nlm:affiliation>Department for Biosystems Science and Engineering, Federal Institute of Technology Zurich and Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland.</nlm:affiliation></affiliation></author><author><name sortKey="Unal, Erkan" sort="Unal, Erkan" uniqKey="Unal E" first="Erkan" last="Unal">Erkan Unal</name><affiliation><nlm:affiliation>1] Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland [2] Department for Biosystems Science and Engineering, Federal Institute of Technology Zurich and Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland.</nlm:affiliation></affiliation></author><author><name sortKey="Liu, Jing" sort="Liu, Jing" uniqKey="Liu J" first="Jing" last="Liu">Jing Liu</name><affiliation><nlm:affiliation>Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Floriot, Sandrine" sort="Floriot, Sandrine" uniqKey="Floriot S" first="Sandrine" last="Floriot">Sandrine Floriot</name><affiliation><nlm:affiliation>Institut National de la Recherche Agronomique, Génétique Animale et Biologie Intégrative, F-78350 Jouy-en-Josas, France.</nlm:affiliation></affiliation></author><author><name sortKey="Barbey, Sarah" sort="Barbey, Sarah" uniqKey="Barbey S" first="Sarah" last="Barbey">Sarah Barbey</name><affiliation><nlm:affiliation>Institut National de la Recherche Agronomique, Domaine Expérimental du Pin au Haras, F-61310 Exmes, France.</nlm:affiliation></affiliation></author><author><name sortKey="Gallard, Yves" sort="Gallard, Yves" uniqKey="Gallard Y" first="Yves" last="Gallard">Yves Gallard</name><affiliation><nlm:affiliation>Institut National de la Recherche Agronomique, Domaine Expérimental du Pin au Haras, F-61310 Exmes, France.</nlm:affiliation></affiliation></author><author><name sortKey="Muller Gerbl, Magdalena" sort="Muller Gerbl, Magdalena" uniqKey="Muller Gerbl M" first="Magdalena" last="Müller-Gerbl">Magdalena Müller-Gerbl</name><affiliation><nlm:affiliation>Institute of Anatomy, Department Biomedicine, University of Basel, CH-4056 Basel, Switzerland.</nlm:affiliation></affiliation></author><author><name sortKey="Courtney, Andrew D" sort="Courtney, Andrew D" uniqKey="Courtney A" first="Andrew D" last="Courtney">Andrew D. Courtney</name><affiliation><nlm:affiliation>Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Klopp, Christophe" sort="Klopp, Christophe" uniqKey="Klopp C" first="Christophe" last="Klopp">Christophe Klopp</name><affiliation><nlm:affiliation>Institut National de la Recherche Agronomique, Biométrie et Intelligence Artificielle, F-31326 Castanet-Tolosan, France.</nlm:affiliation></affiliation></author><author><name sortKey="Rodriguez, Sabrina" sort="Rodriguez, Sabrina" uniqKey="Rodriguez S" first="Sabrina" last="Rodriguez">Sabrina Rodriguez</name><affiliation><nlm:affiliation>1] Institut National de la Recherche Agronomique, Génétique Animale et Biologie Intégrative, F-78350 Jouy-en-Josas, France [2] Institut National de la Recherche Agronomique, Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés, F-31077 Toulouse, France.</nlm:affiliation></affiliation></author><author><name sortKey="Ivanek, Robert" sort="Ivanek, Robert" uniqKey="Ivanek R" first="Robert" last="Ivanek">Robert Ivanek</name><affiliation><nlm:affiliation>1] Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland [2] Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland.</nlm:affiliation></affiliation></author><author><name sortKey="Beisel, Christian" sort="Beisel, Christian" uniqKey="Beisel C" first="Christian" last="Beisel">Christian Beisel</name><affiliation><nlm:affiliation>Department for Biosystems Science and Engineering, Federal Institute of Technology Zurich and Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland.</nlm:affiliation></affiliation></author><author><name sortKey="Wicking, Carol" sort="Wicking, Carol" uniqKey="Wicking C" first="Carol" last="Wicking">Carol Wicking</name><affiliation><nlm:affiliation>Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Iber, Dagmar" sort="Iber, Dagmar" uniqKey="Iber D" first="Dagmar" last="Iber">Dagmar Iber</name><affiliation><nlm:affiliation>Department for Biosystems Science and Engineering, Federal Institute of Technology Zurich and Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland.</nlm:affiliation></affiliation></author><author><name sortKey="Robert, Benoit" sort="Robert, Benoit" uniqKey="Robert B" first="Benoit" last="Robert">Benoit Robert</name><affiliation><nlm:affiliation>Institut Pasteur, Génétique Moléculaire de la Morphogenèse and Centre National de la Recherche Scientifique URA-2578, F-75015 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Mcmahon, Andrew P" sort="Mcmahon, Andrew P" uniqKey="Mcmahon A" first="Andrew P" last="Mcmahon">Andrew P. Mcmahon</name><affiliation><nlm:affiliation>Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Duboule, Denis" sort="Duboule, Denis" uniqKey="Duboule D" first="Denis" last="Duboule">Denis Duboule</name><affiliation><nlm:affiliation>1] School of Life Sciences, Federal Institute of Technology Lausanne, CH-1015 Lausanne, Switzerland [2] Department of Genetics and Evolution, University of Geneva, CH-1211 Geneva, Switzerland.</nlm:affiliation></affiliation></author><author><name sortKey="Zeller, Rolf" sort="Zeller, Rolf" uniqKey="Zeller R" first="Rolf" last="Zeller">Rolf Zeller</name><affiliation><nlm:affiliation>Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:24990743</idno><idno type="pmid">24990743</idno><idno type="doi">10.1038/nature13289</idno><idno type="wicri:Area/PubMed/Corpus">003607</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">003607</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Attenuated sensing of SHH by Ptch1 underlies evolution of bovine limbs.</title><author><name sortKey="Lopez Rios, Javier" sort="Lopez Rios, Javier" uniqKey="Lopez Rios J" first="Javier" last="Lopez-Rios">Javier Lopez-Rios</name><affiliation><nlm:affiliation>1] Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland [2].</nlm:affiliation></affiliation></author><author><name sortKey="Duchesne, Amandine" sort="Duchesne, Amandine" uniqKey="Duchesne A" first="Amandine" last="Duchesne">Amandine Duchesne</name><affiliation><nlm:affiliation>1] Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland [2] Institut National de la Recherche Agronomique, Génétique Animale et Biologie Intégrative, F-78350 Jouy-en-Josas, France [3].</nlm:affiliation></affiliation></author><author><name sortKey="Speziale, Dario" sort="Speziale, Dario" uniqKey="Speziale D" first="Dario" last="Speziale">Dario Speziale</name><affiliation><nlm:affiliation>Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland.</nlm:affiliation></affiliation></author><author><name sortKey="Andrey, Guillaume" sort="Andrey, Guillaume" uniqKey="Andrey G" first="Guillaume" last="Andrey">Guillaume Andrey</name><affiliation><nlm:affiliation>School of Life Sciences, Federal Institute of Technology Lausanne, CH-1015 Lausanne, Switzerland.</nlm:affiliation></affiliation></author><author><name sortKey="Peterson, Kevin A" sort="Peterson, Kevin A" uniqKey="Peterson K" first="Kevin A" last="Peterson">Kevin A. Peterson</name><affiliation><nlm:affiliation>Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Germann, Philipp" sort="Germann, Philipp" uniqKey="Germann P" first="Philipp" last="Germann">Philipp Germann</name><affiliation><nlm:affiliation>Department for Biosystems Science and Engineering, Federal Institute of Technology Zurich and Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland.</nlm:affiliation></affiliation></author><author><name sortKey="Unal, Erkan" sort="Unal, Erkan" uniqKey="Unal E" first="Erkan" last="Unal">Erkan Unal</name><affiliation><nlm:affiliation>1] Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland [2] Department for Biosystems Science and Engineering, Federal Institute of Technology Zurich and Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland.</nlm:affiliation></affiliation></author><author><name sortKey="Liu, Jing" sort="Liu, Jing" uniqKey="Liu J" first="Jing" last="Liu">Jing Liu</name><affiliation><nlm:affiliation>Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Floriot, Sandrine" sort="Floriot, Sandrine" uniqKey="Floriot S" first="Sandrine" last="Floriot">Sandrine Floriot</name><affiliation><nlm:affiliation>Institut National de la Recherche Agronomique, Génétique Animale et Biologie Intégrative, F-78350 Jouy-en-Josas, France.</nlm:affiliation></affiliation></author><author><name sortKey="Barbey, Sarah" sort="Barbey, Sarah" uniqKey="Barbey S" first="Sarah" last="Barbey">Sarah Barbey</name><affiliation><nlm:affiliation>Institut National de la Recherche Agronomique, Domaine Expérimental du Pin au Haras, F-61310 Exmes, France.</nlm:affiliation></affiliation></author><author><name sortKey="Gallard, Yves" sort="Gallard, Yves" uniqKey="Gallard Y" first="Yves" last="Gallard">Yves Gallard</name><affiliation><nlm:affiliation>Institut National de la Recherche Agronomique, Domaine Expérimental du Pin au Haras, F-61310 Exmes, France.</nlm:affiliation></affiliation></author><author><name sortKey="Muller Gerbl, Magdalena" sort="Muller Gerbl, Magdalena" uniqKey="Muller Gerbl M" first="Magdalena" last="Müller-Gerbl">Magdalena Müller-Gerbl</name><affiliation><nlm:affiliation>Institute of Anatomy, Department Biomedicine, University of Basel, CH-4056 Basel, Switzerland.</nlm:affiliation></affiliation></author><author><name sortKey="Courtney, Andrew D" sort="Courtney, Andrew D" uniqKey="Courtney A" first="Andrew D" last="Courtney">Andrew D. Courtney</name><affiliation><nlm:affiliation>Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Klopp, Christophe" sort="Klopp, Christophe" uniqKey="Klopp C" first="Christophe" last="Klopp">Christophe Klopp</name><affiliation><nlm:affiliation>Institut National de la Recherche Agronomique, Biométrie et Intelligence Artificielle, F-31326 Castanet-Tolosan, France.</nlm:affiliation></affiliation></author><author><name sortKey="Rodriguez, Sabrina" sort="Rodriguez, Sabrina" uniqKey="Rodriguez S" first="Sabrina" last="Rodriguez">Sabrina Rodriguez</name><affiliation><nlm:affiliation>1] Institut National de la Recherche Agronomique, Génétique Animale et Biologie Intégrative, F-78350 Jouy-en-Josas, France [2] Institut National de la Recherche Agronomique, Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés, F-31077 Toulouse, France.</nlm:affiliation></affiliation></author><author><name sortKey="Ivanek, Robert" sort="Ivanek, Robert" uniqKey="Ivanek R" first="Robert" last="Ivanek">Robert Ivanek</name><affiliation><nlm:affiliation>1] Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland [2] Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland.</nlm:affiliation></affiliation></author><author><name sortKey="Beisel, Christian" sort="Beisel, Christian" uniqKey="Beisel C" first="Christian" last="Beisel">Christian Beisel</name><affiliation><nlm:affiliation>Department for Biosystems Science and Engineering, Federal Institute of Technology Zurich and Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland.</nlm:affiliation></affiliation></author><author><name sortKey="Wicking, Carol" sort="Wicking, Carol" uniqKey="Wicking C" first="Carol" last="Wicking">Carol Wicking</name><affiliation><nlm:affiliation>Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Iber, Dagmar" sort="Iber, Dagmar" uniqKey="Iber D" first="Dagmar" last="Iber">Dagmar Iber</name><affiliation><nlm:affiliation>Department for Biosystems Science and Engineering, Federal Institute of Technology Zurich and Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland.</nlm:affiliation></affiliation></author><author><name sortKey="Robert, Benoit" sort="Robert, Benoit" uniqKey="Robert B" first="Benoit" last="Robert">Benoit Robert</name><affiliation><nlm:affiliation>Institut Pasteur, Génétique Moléculaire de la Morphogenèse and Centre National de la Recherche Scientifique URA-2578, F-75015 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Mcmahon, Andrew P" sort="Mcmahon, Andrew P" uniqKey="Mcmahon A" first="Andrew P" last="Mcmahon">Andrew P. Mcmahon</name><affiliation><nlm:affiliation>Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Duboule, Denis" sort="Duboule, Denis" uniqKey="Duboule D" first="Denis" last="Duboule">Denis Duboule</name><affiliation><nlm:affiliation>1] School of Life Sciences, Federal Institute of Technology Lausanne, CH-1015 Lausanne, Switzerland [2] Department of Genetics and Evolution, University of Geneva, CH-1211 Geneva, Switzerland.</nlm:affiliation></affiliation></author><author><name sortKey="Zeller, Rolf" sort="Zeller, Rolf" uniqKey="Zeller R" first="Rolf" last="Zeller">Rolf Zeller</name><affiliation><nlm:affiliation>Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Nature</title><idno type="eISSN">1476-4687</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Biological Evolution</term><term>Body Patterning</term><term>Cattle</term><term>Extremities (anatomy & histology)</term><term>Extremities (embryology)</term><term>Female</term><term>Gene Expression Regulation, Developmental (genetics)</term><term>Hedgehog Proteins (metabolism)</term><term>Limb Buds (anatomy & histology)</term><term>Limb Buds (embryology)</term><term>Male</term><term>Mesoderm (metabolism)</term><term>Mice</term><term>Mice, Transgenic</term><term>Patched Receptors</term><term>Patched-1 Receptor</term><term>Receptors, Cell Surface (genetics)</term><term>Receptors, Cell Surface (metabolism)</term><term>Regulatory Sequences, Nucleic Acid (genetics)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Receptors, Cell Surface</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Hedgehog Proteins</term><term>Receptors, Cell Surface</term></keywords><keywords scheme="MESH" qualifier="anatomy & histology" xml:lang="en"><term>Extremities</term><term>Limb Buds</term></keywords><keywords scheme="MESH" qualifier="embryology" xml:lang="en"><term>Extremities</term><term>Limb Buds</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Gene Expression Regulation, Developmental</term><term>Regulatory Sequences, Nucleic Acid</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Mesoderm</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Biological Evolution</term><term>Body Patterning</term><term>Cattle</term><term>Female</term><term>Male</term><term>Mice</term><term>Mice, Transgenic</term><term>Patched Receptors</term><term>Patched-1 Receptor</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The large spectrum of limb morphologies reflects the wide evolutionary diversification of the basic pentadactyl pattern in tetrapods. In even-toed ungulates (artiodactyls, including cattle), limbs are adapted for running as a consequence of progressive reduction of their distal skeleton to symmetrical and elongated middle digits with hoofed phalanges. Here we analyse bovine embryos to establish that polarized gene expression is progressively lost during limb development in comparison to the mouse. Notably, the transcriptional upregulation of the Ptch1 gene, which encodes a Sonic hedgehog (SHH) receptor, is disrupted specifically in the bovine limb bud mesenchyme. This is due to evolutionary alteration of a Ptch1 cis-regulatory module, which no longer responds to graded SHH signalling during bovine handplate development. Our study provides a molecular explanation for the loss of digit asymmetry in bovine limb buds and suggests that modifications affecting the Ptch1 cis-regulatory landscape have contributed to evolutionary diversification of artiodactyl limbs.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">24990743</PMID><DateCreated><Year>2014</Year><Month>07</Month><Day>03</Day></DateCreated><DateCompleted><Year>2014</Year><Month>08</Month><Day>15</Day></DateCompleted><DateRevised><Year>2017</Year><Month>02</Month><Day>20</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1476-4687</ISSN><JournalIssue CitedMedium="Internet"><Volume>511</Volume><Issue>7507</Issue><PubDate><Year>2014</Year><Month>Jul</Month><Day>03</Day></PubDate></JournalIssue><Title>Nature</Title><ISOAbbreviation>Nature</ISOAbbreviation></Journal><ArticleTitle>Attenuated sensing of SHH by Ptch1 underlies evolution of bovine limbs.</ArticleTitle><Pagination><MedlinePgn>46-51</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/nature13289</ELocationID><Abstract><AbstractText>The large spectrum of limb morphologies reflects the wide evolutionary diversification of the basic pentadactyl pattern in tetrapods. In even-toed ungulates (artiodactyls, including cattle), limbs are adapted for running as a consequence of progressive reduction of their distal skeleton to symmetrical and elongated middle digits with hoofed phalanges. Here we analyse bovine embryos to establish that polarized gene expression is progressively lost during limb development in comparison to the mouse. Notably, the transcriptional upregulation of the Ptch1 gene, which encodes a Sonic hedgehog (SHH) receptor, is disrupted specifically in the bovine limb bud mesenchyme. This is due to evolutionary alteration of a Ptch1 cis-regulatory module, which no longer responds to graded SHH signalling during bovine handplate development. Our study provides a molecular explanation for the loss of digit asymmetry in bovine limb buds and suggests that modifications affecting the Ptch1 cis-regulatory landscape have contributed to evolutionary diversification of artiodactyl limbs.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Lopez-Rios</LastName><ForeName>Javier</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>1] Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland [2].</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Duchesne</LastName><ForeName>Amandine</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>1] Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland [2] Institut National de la Recherche Agronomique, Génétique Animale et Biologie Intégrative, F-78350 Jouy-en-Josas, France [3].</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Speziale</LastName><ForeName>Dario</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Andrey</LastName><ForeName>Guillaume</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>School of Life Sciences, Federal Institute of Technology Lausanne, CH-1015 Lausanne, Switzerland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Peterson</LastName><ForeName>Kevin A</ForeName><Initials>KA</Initials><AffiliationInfo><Affiliation>Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Germann</LastName><ForeName>Philipp</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department for Biosystems Science and Engineering, Federal Institute of Technology Zurich and Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Unal</LastName><ForeName>Erkan</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>1] Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland [2] Department for Biosystems Science and Engineering, Federal Institute of Technology Zurich and Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Jing</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Floriot</LastName><ForeName>Sandrine</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Institut National de la Recherche Agronomique, Génétique Animale et Biologie Intégrative, F-78350 Jouy-en-Josas, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Barbey</LastName><ForeName>Sarah</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Institut National de la Recherche Agronomique, Domaine Expérimental du Pin au Haras, F-61310 Exmes, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gallard</LastName><ForeName>Yves</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Institut National de la Recherche Agronomique, Domaine Expérimental du Pin au Haras, F-61310 Exmes, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Müller-Gerbl</LastName><ForeName>Magdalena</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Institute of Anatomy, Department Biomedicine, University of Basel, CH-4056 Basel, Switzerland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Courtney</LastName><ForeName>Andrew D</ForeName><Initials>AD</Initials><AffiliationInfo><Affiliation>Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Klopp</LastName><ForeName>Christophe</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Institut National de la Recherche Agronomique, Biométrie et Intelligence Artificielle, F-31326 Castanet-Tolosan, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rodriguez</LastName><ForeName>Sabrina</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>1] Institut National de la Recherche Agronomique, Génétique Animale et Biologie Intégrative, F-78350 Jouy-en-Josas, France [2] Institut National de la Recherche Agronomique, Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés, F-31077 Toulouse, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ivanek</LastName><ForeName>Robert</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>1] Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland [2] Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Beisel</LastName><ForeName>Christian</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department for Biosystems Science and Engineering, Federal Institute of Technology Zurich and Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wicking</LastName><ForeName>Carol</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Iber</LastName><ForeName>Dagmar</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Department for Biosystems Science and Engineering, Federal Institute of Technology Zurich and Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Robert</LastName><ForeName>Benoit</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Institut Pasteur, Génétique Moléculaire de la Morphogenèse and Centre National de la Recherche Scientifique URA-2578, F-75015 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>McMahon</LastName><ForeName>Andrew P</ForeName><Initials>AP</Initials><AffiliationInfo><Affiliation>Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Duboule</LastName><ForeName>Denis</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>1] School of Life Sciences, Federal Institute of Technology Lausanne, CH-1015 Lausanne, Switzerland [2] Department of Genetics and Evolution, University of Geneva, CH-1211 Geneva, Switzerland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zeller</LastName><ForeName>Rolf</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><DataBankList CompleteYN="Y"><DataBank><DataBankName>GEO</DataBankName><AccessionNumberList><AccessionNumber>GSE52939</AccessionNumber><AccessionNumber>GSE52988</AccessionNumber></AccessionNumberList></DataBank></DataBankList><GrantList CompleteYN="Y"><Grant><GrantID>NS 033642</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D013486">Research Support, U.S. Gov't, Non-P.H.S.</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2014</Year><Month>06</Month><Day>18</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Nature</MedlineTA><NlmUniqueID>0410462</NlmUniqueID><ISSNLinking>0028-0836</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D053823">Hedgehog Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000072079">Patched Receptors</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000072081">Patched-1 Receptor</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C000606240">Ptch1 protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011956">Receptors, Cell Surface</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections 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