1. Attenuated sensing of SHH by Ptch1 underlies evolution of bovine limbs
- Author
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Dario Speziale, Sabrina Rodriguez, Andrew D. Courtney, Benoît Robert, Sandrine Floriot, Christophe Klopp, Jing Liu, Dagmar Iber, Philipp Germann, Javier Lopez-Rios, Christian Beisel, Yves Gallard, Amandine Duchesne, Sarah Barbey, Magdalena Müller-Gerbl, Denis Duboule, Carol Wicking, Robert Ivanek, Guillaume Andrey, Rolf Zeller, Kevin A. Peterson, Erkan Ünal, Andrew P. McMahon, Developmental Genetics, Department Biomedicine, University of Basel (Unibas), Génétique Animale et Biologie Intégrative (GABI), AgroParisTech-Institut National de la Recherche Agronomique (INRA), School of Life Sciences, Federal Institute of Technology Lausann, 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 (USC), Department of Biosystems Science and Engineering [ETH Zürich] (D-BSSE), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Domaine expérimental animal du Pin (SEA), Institut National de la Recherche Agronomique (INRA), Institute of Anatomy, Department Biomedicine, Institute for Molecular Bioscience, University of Queensland [Brisbane], Unité de Biométrie et Intelligence Artificielle (UBIA), Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Swiss Institute of Bioinformatics, Génétique Moléculaire de la Morphogénèse, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Department of Genetics and Evolution, Université de Genève (UNIGE), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Domaine Expérimental du Pin (DEP), Unité de Biométrie et Intelligence Artificielle (ancêtre de MIAT) (UBIA), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne = University of Lausanne (UNIL), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université de Genève = University of Geneva (UNIGE), Université de Lausanne (UNIL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]
- Subjects
Male ,Patched Receptors ,Extremities/anatomy & histology/embryology ,Mesenchyme ,[SDV]Life Sciences [q-bio] ,Cell Surface/genetics/metabolism ,Transgenic ,Limb Buds/anatomy & histology/embryology ,Mice ,03 medical and health sciences ,Limb bud ,0302 clinical medicine ,ddc:590 ,Nucleic Acid/genetics ,Receptors ,Gene expression ,medicine ,Animals ,Hedgehog Proteins/metabolism ,Limb development ,Sonic hedgehog ,Body Patterning ,030304 developmental biology ,Regulation of gene expression ,Mesoderm/metabolism ,0303 health sciences ,Multidisciplinary ,biology ,Anatomy ,Biological Evolution ,Cell biology ,Patched-1 Receptor ,body regions ,Developmental/genetics ,medicine.anatomical_structure ,Gene Expression Regulation ,PTCH1 ,biology.protein ,Evolutionary developmental biology ,Cattle ,Female ,Regulatory Sequences ,030217 neurology & neurosurgery - Abstract
Chantier qualité spécifique "Auteurs Externes" département de Génétique animale : uniquement liaison auteur au référentiel HR-Access; 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.
- Published
- 2014
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