Attenuated sensing of SHH by Ptch1 underlies evolution of bovine limbs.
Identifieur interne : 003B85 ( Main/Exploration ); précédent : 003B84; suivant : 003B86Attenuated sensing of SHH by Ptch1 underlies evolution of bovine limbs.
Auteurs : Javier Lopez-Rios ; Amandine Duchesne ; Dario Speziale [Suisse] ; Guillaume Andrey [Suisse] ; Kevin A. Peterson [États-Unis] ; Philipp Germann [Suisse] ; Erkan Unal [Suisse] ; Jing Liu [États-Unis] ; Sandrine Floriot [France] ; Sarah Barbey [France] ; Yves Gallard [France] ; Magdalena Müller-Gerbl [Suisse] ; Andrew D. Courtney [Australie] ; Christophe Klopp [France] ; Sabrina Rodriguez [France] ; Robert Ivanek [Suisse] ; Christian Beisel [Suisse] ; Carol Wicking [Australie] ; Dagmar Iber [Suisse] ; Benoit Robert [France] ; Andrew P. Mcmahon [États-Unis] ; Denis Duboule [Suisse] ; Rolf Zeller [Suisse]Source :
- Nature [ 1476-4687 ] ; 2014.
Descripteurs français
- KwdFr :
- Animaux, Bourgeons de membre (anatomie et histologie), Bourgeons de membre (embryologie), Bovins, Femelle, Membres (anatomie et histologie), Membres (embryologie), Mâle, Mésoderme (métabolisme), Plan d'organisation du corps, Protéines Hedgehog (métabolisme), Récepteur Patched-1, Récepteurs de surface cellulaire (génétique), Récepteurs de surface cellulaire (métabolisme), Récepteurs patched, Régulation de l'expression des gènes au cours du développement (génétique), Souris, Souris transgéniques, Séquences d'acides nucléiques régulatrices (génétique), Évolution biologique.
- MESH :
- anatomie et histologie : Bourgeons de membre, Membres.
- embryologie : Bourgeons de membre, Membres.
- génétique : Récepteurs de surface cellulaire, Régulation de l'expression des gènes au cours du développement, Séquences d'acides nucléiques régulatrices.
- métabolisme : Mésoderme, Protéines Hedgehog, Récepteurs de surface cellulaire.
- Animaux, Bovins, Femelle, Mâle, Plan d'organisation du corps, Récepteur Patched-1, Récepteurs patched, Souris, Souris transgéniques, Évolution biologique.
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
Affiliations:
- Australie, France, Suisse, États-Unis
- Californie, Canton de Genève
- Genève, Los Angeles
- Université de Californie du Sud, Université de Genève
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Le document en format XML
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wicri:level="1"><nlm:affiliation>Department for Biosystems Science and Engineering, Federal Institute of Technology Zurich and Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department for Biosystems Science and Engineering, Federal Institute of Technology Zurich and Swiss Institute of Bioinformatics, CH-4058 Basel</wicri:regionArea><wicri:noRegion>CH-4058 Basel</wicri:noRegion></affiliation></author><author><name sortKey="Unal, Erkan" sort="Unal, Erkan" uniqKey="Unal E" first="Erkan" last="Unal">Erkan Unal</name><affiliation wicri:level="1"><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><country xml:lang="fr">Suisse</country><wicri:regionArea>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</wicri:regionArea><wicri:noRegion>CH-4058 Basel</wicri:noRegion></affiliation></author><author><name sortKey="Liu, Jing" sort="Liu, Jing" uniqKey="Liu J" first="Jing" last="Liu">Jing Liu</name><affiliation wicri:level="4"><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><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><orgName type="university">Université de Californie du Sud</orgName><placeName><settlement type="city">Los Angeles</settlement><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Floriot, Sandrine" sort="Floriot, Sandrine" uniqKey="Floriot S" first="Sandrine" last="Floriot">Sandrine Floriot</name><affiliation wicri:level="1"><nlm:affiliation>Institut National de la Recherche Agronomique, Génétique Animale et Biologie Intégrative, F-78350 Jouy-en-Josas, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Recherche Agronomique, Génétique Animale et Biologie Intégrative, F-78350 Jouy-en-Josas</wicri:regionArea><wicri:noRegion>78350 Jouy-en-Josas</wicri:noRegion><wicri:noRegion>78350 Jouy-en-Josas</wicri:noRegion></affiliation></author><author><name sortKey="Barbey, Sarah" sort="Barbey, Sarah" uniqKey="Barbey S" first="Sarah" last="Barbey">Sarah Barbey</name><affiliation wicri:level="1"><nlm:affiliation>Institut National de la Recherche Agronomique, Domaine Expérimental du Pin au Haras, F-61310 Exmes, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Recherche Agronomique, Domaine Expérimental du Pin au Haras, F-61310 Exmes</wicri:regionArea><wicri:noRegion>61310 Exmes</wicri:noRegion><wicri:noRegion>61310 Exmes</wicri:noRegion></affiliation></author><author><name sortKey="Gallard, Yves" sort="Gallard, Yves" uniqKey="Gallard Y" first="Yves" last="Gallard">Yves Gallard</name><affiliation wicri:level="1"><nlm:affiliation>Institut National de la Recherche Agronomique, Domaine Expérimental du Pin au Haras, F-61310 Exmes, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Recherche Agronomique, Domaine Expérimental du Pin au Haras, F-61310 Exmes</wicri:regionArea><wicri:noRegion>61310 Exmes</wicri:noRegion><wicri:noRegion>61310 Exmes</wicri:noRegion></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 wicri:level="1"><nlm:affiliation>Institute of Anatomy, Department Biomedicine, University of Basel, CH-4056 Basel, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Anatomy, Department Biomedicine, University of Basel, CH-4056 Basel</wicri:regionArea><wicri:noRegion>CH-4056 Basel</wicri:noRegion></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 wicri:level="1"><nlm:affiliation>Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072</wicri:regionArea><wicri:noRegion>Queensland 4072</wicri:noRegion></affiliation></author><author><name sortKey="Klopp, Christophe" sort="Klopp, Christophe" uniqKey="Klopp C" first="Christophe" last="Klopp">Christophe Klopp</name><affiliation wicri:level="1"><nlm:affiliation>Institut National de la Recherche Agronomique, Biométrie et Intelligence Artificielle, F-31326 Castanet-Tolosan, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Recherche Agronomique, Biométrie et Intelligence Artificielle, F-31326 Castanet-Tolosan</wicri:regionArea><wicri:noRegion>31326 Castanet-Tolosan</wicri:noRegion><wicri:noRegion>31326 Castanet-Tolosan</wicri:noRegion></affiliation></author><author><name sortKey="Rodriguez, Sabrina" sort="Rodriguez, Sabrina" uniqKey="Rodriguez S" first="Sabrina" last="Rodriguez">Sabrina Rodriguez</name><affiliation wicri:level="1"><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><country xml:lang="fr">France</country><wicri:regionArea>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</wicri:regionArea><wicri:noRegion>31077 Toulouse</wicri:noRegion><wicri:noRegion>31077 Toulouse</wicri:noRegion></affiliation></author><author><name sortKey="Ivanek, Robert" sort="Ivanek, Robert" uniqKey="Ivanek R" first="Robert" last="Ivanek">Robert Ivanek</name><affiliation wicri:level="1"><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><country xml:lang="fr">Suisse</country><wicri:regionArea>1] Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland [2] Swiss Institute of Bioinformatics, CH-4058 Basel</wicri:regionArea><wicri:noRegion>CH-4058 Basel</wicri:noRegion></affiliation></author><author><name sortKey="Beisel, Christian" sort="Beisel, Christian" uniqKey="Beisel C" first="Christian" last="Beisel">Christian Beisel</name><affiliation wicri:level="1"><nlm:affiliation>Department for Biosystems Science and Engineering, Federal Institute of Technology Zurich and Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department for Biosystems Science and Engineering, Federal Institute of Technology Zurich and Swiss Institute of Bioinformatics, CH-4058 Basel</wicri:regionArea><wicri:noRegion>CH-4058 Basel</wicri:noRegion></affiliation></author><author><name sortKey="Wicking, Carol" sort="Wicking, Carol" uniqKey="Wicking C" first="Carol" last="Wicking">Carol Wicking</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072</wicri:regionArea><wicri:noRegion>Queensland 4072</wicri:noRegion></affiliation></author><author><name sortKey="Iber, Dagmar" sort="Iber, Dagmar" uniqKey="Iber D" first="Dagmar" last="Iber">Dagmar Iber</name><affiliation wicri:level="1"><nlm:affiliation>Department for Biosystems Science and Engineering, Federal Institute of Technology Zurich and Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department for Biosystems Science and Engineering, Federal Institute of Technology Zurich and Swiss Institute of Bioinformatics, CH-4058 Basel</wicri:regionArea><wicri:noRegion>CH-4058 Basel</wicri:noRegion></affiliation></author><author><name sortKey="Robert, Benoit" sort="Robert, Benoit" uniqKey="Robert B" first="Benoit" last="Robert">Benoit Robert</name><affiliation wicri:level="1"><nlm:affiliation>Institut Pasteur, Génétique Moléculaire de la Morphogenèse and Centre National de la Recherche Scientifique URA-2578, F-75015 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut Pasteur, Génétique Moléculaire de la Morphogenèse and Centre National de la Recherche Scientifique URA-2578, F-75015 Paris</wicri:regionArea><wicri:noRegion>75015 Paris</wicri:noRegion><wicri:noRegion>75015 Paris</wicri:noRegion></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 wicri:level="4"><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><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><orgName type="university">Université de Californie du Sud</orgName><placeName><settlement type="city">Los Angeles</settlement><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Duboule, Denis" sort="Duboule, Denis" uniqKey="Duboule D" first="Denis" last="Duboule">Denis Duboule</name><affiliation wicri:level="4"><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><country xml:lang="fr">Suisse</country><wicri:regionArea>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</wicri:regionArea><orgName type="university">Université de Genève</orgName><placeName><settlement type="city">Genève</settlement><region nuts="3" type="region">Canton de Genève</region></placeName></affiliation></author><author><name sortKey="Zeller, Rolf" sort="Zeller, Rolf" uniqKey="Zeller R" first="Rolf" last="Zeller">Rolf Zeller</name><affiliation wicri:level="1"><nlm:affiliation>Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel</wicri:regionArea><wicri:noRegion>CH-4058 Basel</wicri:noRegion></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><idno type="wicri:Area/PubMed/Curation">003494</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">003494</idno><idno type="wicri:Area/PubMed/Checkpoint">003494</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">003494</idno><idno type="wicri:Area/Ncbi/Merge">001B93</idno><idno type="wicri:Area/Ncbi/Curation">001B93</idno><idno 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Basel, Switzerland [2] Institut National de la Recherche Agronomique, Génétique Animale et Biologie Intégrative, F-78350 Jouy-en-Josas, France [3].</nlm:affiliation><wicri:noCountry code="subField">France [3]</wicri:noCountry></affiliation></author><author><name sortKey="Speziale, Dario" sort="Speziale, Dario" uniqKey="Speziale D" first="Dario" last="Speziale">Dario Speziale</name><affiliation wicri:level="1"><nlm:affiliation>Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel</wicri:regionArea><wicri:noRegion>CH-4058 Basel</wicri:noRegion></affiliation></author><author><name sortKey="Andrey, Guillaume" sort="Andrey, Guillaume" uniqKey="Andrey G" first="Guillaume" last="Andrey">Guillaume Andrey</name><affiliation wicri:level="1"><nlm:affiliation>School of Life Sciences, Federal Institute of Technology Lausanne, CH-1015 Lausanne, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>School of Life Sciences, Federal Institute of Technology Lausanne, CH-1015 Lausanne</wicri:regionArea><wicri:noRegion>CH-1015 Lausanne</wicri:noRegion></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 wicri:level="4"><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><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><orgName type="university">Université de Californie du Sud</orgName><placeName><settlement type="city">Los Angeles</settlement><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Germann, Philipp" sort="Germann, Philipp" uniqKey="Germann P" first="Philipp" last="Germann">Philipp Germann</name><affiliation wicri:level="1"><nlm:affiliation>Department for Biosystems Science and Engineering, Federal Institute of Technology Zurich and Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department for Biosystems Science and Engineering, Federal Institute of Technology Zurich and Swiss Institute of Bioinformatics, CH-4058 Basel</wicri:regionArea><wicri:noRegion>CH-4058 Basel</wicri:noRegion></affiliation></author><author><name sortKey="Unal, Erkan" sort="Unal, Erkan" uniqKey="Unal E" first="Erkan" last="Unal">Erkan Unal</name><affiliation wicri:level="1"><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><country xml:lang="fr">Suisse</country><wicri:regionArea>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</wicri:regionArea><wicri:noRegion>CH-4058 Basel</wicri:noRegion></affiliation></author><author><name sortKey="Liu, Jing" sort="Liu, Jing" uniqKey="Liu J" first="Jing" last="Liu">Jing Liu</name><affiliation wicri:level="4"><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><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><orgName type="university">Université de Californie du Sud</orgName><placeName><settlement type="city">Los Angeles</settlement><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Floriot, Sandrine" sort="Floriot, Sandrine" uniqKey="Floriot S" first="Sandrine" last="Floriot">Sandrine Floriot</name><affiliation wicri:level="1"><nlm:affiliation>Institut National de la Recherche Agronomique, Génétique Animale et Biologie Intégrative, F-78350 Jouy-en-Josas, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Recherche Agronomique, Génétique Animale et Biologie Intégrative, F-78350 Jouy-en-Josas</wicri:regionArea><wicri:noRegion>78350 Jouy-en-Josas</wicri:noRegion><wicri:noRegion>78350 Jouy-en-Josas</wicri:noRegion></affiliation></author><author><name sortKey="Barbey, Sarah" sort="Barbey, Sarah" uniqKey="Barbey S" first="Sarah" last="Barbey">Sarah Barbey</name><affiliation wicri:level="1"><nlm:affiliation>Institut National de la Recherche Agronomique, Domaine Expérimental du Pin au Haras, F-61310 Exmes, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Recherche Agronomique, Domaine Expérimental du Pin au Haras, F-61310 Exmes</wicri:regionArea><wicri:noRegion>61310 Exmes</wicri:noRegion><wicri:noRegion>61310 Exmes</wicri:noRegion></affiliation></author><author><name sortKey="Gallard, Yves" sort="Gallard, Yves" uniqKey="Gallard Y" first="Yves" last="Gallard">Yves Gallard</name><affiliation wicri:level="1"><nlm:affiliation>Institut National de la Recherche Agronomique, Domaine Expérimental du Pin au Haras, F-61310 Exmes, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Recherche Agronomique, Domaine Expérimental du Pin au Haras, F-61310 Exmes</wicri:regionArea><wicri:noRegion>61310 Exmes</wicri:noRegion><wicri:noRegion>61310 Exmes</wicri:noRegion></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 wicri:level="1"><nlm:affiliation>Institute of Anatomy, Department Biomedicine, University of Basel, CH-4056 Basel, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Anatomy, Department Biomedicine, University of Basel, CH-4056 Basel</wicri:regionArea><wicri:noRegion>CH-4056 Basel</wicri:noRegion></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 wicri:level="1"><nlm:affiliation>Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072</wicri:regionArea><wicri:noRegion>Queensland 4072</wicri:noRegion></affiliation></author><author><name sortKey="Klopp, Christophe" sort="Klopp, Christophe" uniqKey="Klopp C" first="Christophe" last="Klopp">Christophe Klopp</name><affiliation wicri:level="1"><nlm:affiliation>Institut National de la Recherche Agronomique, Biométrie et Intelligence Artificielle, F-31326 Castanet-Tolosan, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Recherche Agronomique, Biométrie et Intelligence Artificielle, F-31326 Castanet-Tolosan</wicri:regionArea><wicri:noRegion>31326 Castanet-Tolosan</wicri:noRegion><wicri:noRegion>31326 Castanet-Tolosan</wicri:noRegion></affiliation></author><author><name sortKey="Rodriguez, Sabrina" sort="Rodriguez, Sabrina" uniqKey="Rodriguez S" first="Sabrina" last="Rodriguez">Sabrina Rodriguez</name><affiliation wicri:level="1"><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><country xml:lang="fr">France</country><wicri:regionArea>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</wicri:regionArea><wicri:noRegion>31077 Toulouse</wicri:noRegion><wicri:noRegion>31077 Toulouse</wicri:noRegion></affiliation></author><author><name sortKey="Ivanek, Robert" sort="Ivanek, Robert" uniqKey="Ivanek R" first="Robert" last="Ivanek">Robert Ivanek</name><affiliation wicri:level="1"><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><country xml:lang="fr">Suisse</country><wicri:regionArea>1] Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland [2] Swiss Institute of Bioinformatics, CH-4058 Basel</wicri:regionArea><wicri:noRegion>CH-4058 Basel</wicri:noRegion></affiliation></author><author><name sortKey="Beisel, Christian" sort="Beisel, Christian" uniqKey="Beisel C" first="Christian" last="Beisel">Christian Beisel</name><affiliation wicri:level="1"><nlm:affiliation>Department for Biosystems Science and Engineering, Federal Institute of Technology Zurich and Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department for Biosystems Science and Engineering, Federal Institute of Technology Zurich and Swiss Institute of Bioinformatics, CH-4058 Basel</wicri:regionArea><wicri:noRegion>CH-4058 Basel</wicri:noRegion></affiliation></author><author><name sortKey="Wicking, Carol" sort="Wicking, Carol" uniqKey="Wicking C" first="Carol" last="Wicking">Carol Wicking</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072</wicri:regionArea><wicri:noRegion>Queensland 4072</wicri:noRegion></affiliation></author><author><name sortKey="Iber, Dagmar" sort="Iber, Dagmar" uniqKey="Iber D" first="Dagmar" last="Iber">Dagmar Iber</name><affiliation wicri:level="1"><nlm:affiliation>Department for Biosystems Science and Engineering, Federal Institute of Technology Zurich and Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department for Biosystems Science and Engineering, Federal Institute of Technology Zurich and Swiss Institute of Bioinformatics, CH-4058 Basel</wicri:regionArea><wicri:noRegion>CH-4058 Basel</wicri:noRegion></affiliation></author><author><name sortKey="Robert, Benoit" sort="Robert, Benoit" uniqKey="Robert B" first="Benoit" last="Robert">Benoit Robert</name><affiliation wicri:level="1"><nlm:affiliation>Institut Pasteur, Génétique Moléculaire de la Morphogenèse and Centre National de la Recherche Scientifique URA-2578, F-75015 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut Pasteur, Génétique Moléculaire de la Morphogenèse and Centre National de la Recherche Scientifique URA-2578, F-75015 Paris</wicri:regionArea><wicri:noRegion>75015 Paris</wicri:noRegion><wicri:noRegion>75015 Paris</wicri:noRegion></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 wicri:level="4"><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><country xml:lang="fr">États-Unis</country><wicri:regionArea>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</wicri:regionArea><orgName type="university">Université de Californie du Sud</orgName><placeName><settlement type="city">Los Angeles</settlement><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Duboule, Denis" sort="Duboule, Denis" uniqKey="Duboule D" first="Denis" last="Duboule">Denis Duboule</name><affiliation wicri:level="4"><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><country xml:lang="fr">Suisse</country><wicri:regionArea>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</wicri:regionArea><orgName type="university">Université de Genève</orgName><placeName><settlement type="city">Genève</settlement><region nuts="3" type="region">Canton de Genève</region></placeName></affiliation></author><author><name sortKey="Zeller, Rolf" sort="Zeller, Rolf" uniqKey="Zeller R" first="Rolf" last="Zeller">Rolf Zeller</name><affiliation wicri:level="1"><nlm:affiliation>Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel</wicri:regionArea><wicri:noRegion>CH-4058 Basel</wicri:noRegion></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="KwdFr" xml:lang="fr"><term>Animaux</term><term>Bourgeons de membre (anatomie et histologie)</term><term>Bourgeons de membre (embryologie)</term><term>Bovins</term><term>Femelle</term><term>Membres (anatomie et histologie)</term><term>Membres (embryologie)</term><term>Mâle</term><term>Mésoderme (métabolisme)</term><term>Plan d'organisation du corps</term><term>Protéines Hedgehog (métabolisme)</term><term>Récepteur Patched-1</term><term>Récepteurs de surface cellulaire (génétique)</term><term>Récepteurs de surface cellulaire (métabolisme)</term><term>Récepteurs patched</term><term>Régulation de l'expression des gènes au cours du développement (génétique)</term><term>Souris</term><term>Souris transgéniques</term><term>Séquences d'acides nucléiques régulatrices (génétique)</term><term>Évolution biologique</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="anatomie et histologie" xml:lang="fr"><term>Bourgeons de membre</term><term>Membres</term></keywords><keywords scheme="MESH" qualifier="anatomy & histology" xml:lang="en"><term>Extremities</term><term>Limb Buds</term></keywords><keywords scheme="MESH" qualifier="embryologie" xml:lang="fr"><term>Bourgeons de membre</term><term>Membres</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="génétique" xml:lang="fr"><term>Récepteurs de surface cellulaire</term><term>Régulation de l'expression des gènes au cours du développement</term><term>Séquences d'acides nucléiques régulatrices</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Mesoderm</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Mésoderme</term><term>Protéines Hedgehog</term><term>Récepteurs de surface cellulaire</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><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Bovins</term><term>Femelle</term><term>Mâle</term><term>Plan d'organisation du corps</term><term>Récepteur Patched-1</term><term>Récepteurs patched</term><term>Souris</term><term>Souris transgéniques</term><term>Évolution biologique</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><affiliations><list><country><li>Australie</li><li>France</li><li>Suisse</li><li>États-Unis</li></country><region><li>Californie</li><li>Canton de Genève</li></region><settlement><li>Genève</li><li>Los Angeles</li></settlement><orgName><li>Université de Californie du Sud</li><li>Université de Genève</li></orgName></list><tree><noCountry><name sortKey="Duchesne, Amandine" sort="Duchesne, Amandine" uniqKey="Duchesne A" first="Amandine" last="Duchesne">Amandine Duchesne</name><name sortKey="Lopez Rios, Javier" sort="Lopez Rios, Javier" uniqKey="Lopez Rios J" first="Javier" last="Lopez-Rios">Javier Lopez-Rios</name></noCountry><country name="Suisse"><noRegion><name sortKey="Speziale, Dario" sort="Speziale, Dario" uniqKey="Speziale D" first="Dario" last="Speziale">Dario Speziale</name></noRegion><name sortKey="Andrey, Guillaume" sort="Andrey, Guillaume" uniqKey="Andrey G" first="Guillaume" last="Andrey">Guillaume Andrey</name><name sortKey="Beisel, Christian" sort="Beisel, Christian" uniqKey="Beisel C" first="Christian" last="Beisel">Christian Beisel</name><name sortKey="Duboule, Denis" sort="Duboule, Denis" uniqKey="Duboule D" first="Denis" last="Duboule">Denis Duboule</name><name sortKey="Germann, Philipp" sort="Germann, Philipp" uniqKey="Germann P" first="Philipp" last="Germann">Philipp Germann</name><name sortKey="Iber, Dagmar" sort="Iber, Dagmar" uniqKey="Iber D" first="Dagmar" last="Iber">Dagmar Iber</name><name sortKey="Ivanek, Robert" sort="Ivanek, Robert" uniqKey="Ivanek R" first="Robert" last="Ivanek">Robert Ivanek</name><name sortKey="Muller Gerbl, Magdalena" sort="Muller Gerbl, Magdalena" uniqKey="Muller Gerbl M" first="Magdalena" last="Müller-Gerbl">Magdalena Müller-Gerbl</name><name sortKey="Unal, Erkan" sort="Unal, Erkan" uniqKey="Unal E" first="Erkan" last="Unal">Erkan Unal</name><name sortKey="Zeller, Rolf" sort="Zeller, Rolf" uniqKey="Zeller R" first="Rolf" last="Zeller">Rolf Zeller</name></country><country name="États-Unis"><region name="Californie"><name sortKey="Peterson, Kevin A" sort="Peterson, Kevin A" uniqKey="Peterson K" first="Kevin A" last="Peterson">Kevin A. Peterson</name></region><name sortKey="Liu, Jing" sort="Liu, Jing" uniqKey="Liu J" first="Jing" last="Liu">Jing Liu</name><name sortKey="Mcmahon, Andrew P" sort="Mcmahon, Andrew P" uniqKey="Mcmahon A" first="Andrew P" last="Mcmahon">Andrew P. Mcmahon</name></country><country name="France"><noRegion><name sortKey="Floriot, Sandrine" sort="Floriot, Sandrine" uniqKey="Floriot S" first="Sandrine" last="Floriot">Sandrine Floriot</name></noRegion><name sortKey="Barbey, Sarah" sort="Barbey, Sarah" uniqKey="Barbey S" first="Sarah" last="Barbey">Sarah Barbey</name><name sortKey="Gallard, Yves" sort="Gallard, Yves" uniqKey="Gallard Y" first="Yves" last="Gallard">Yves Gallard</name><name sortKey="Klopp, Christophe" sort="Klopp, Christophe" uniqKey="Klopp C" first="Christophe" last="Klopp">Christophe Klopp</name><name sortKey="Robert, Benoit" sort="Robert, Benoit" uniqKey="Robert B" first="Benoit" last="Robert">Benoit Robert</name><name sortKey="Rodriguez, Sabrina" sort="Rodriguez, Sabrina" uniqKey="Rodriguez S" first="Sabrina" last="Rodriguez">Sabrina Rodriguez</name></country><country name="Australie"><noRegion><name sortKey="Courtney, Andrew D" sort="Courtney, Andrew D" uniqKey="Courtney A" first="Andrew D" last="Courtney">Andrew D. Courtney</name></noRegion><name sortKey="Wicking, Carol" sort="Wicking, Carol" uniqKey="Wicking C" first="Carol" last="Wicking">Carol Wicking</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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