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Nature. 2014 Jul 3;511(7507):46-51. doi: 10.1038/nature13289. Epub 2014 Jun 18.

Attenuated sensing of SHH by Ptch1 underlies evolution of bovine limbs.

Author information

  • 11] Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland [2].
  • 21] 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].
  • 3Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland.
  • 4School of Life Sciences, Federal Institute of Technology Lausanne, CH-1015 Lausanne, Switzerland.
  • 5Department 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.
  • 6Department for Biosystems Science and Engineering, Federal Institute of Technology Zurich and Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland.
  • 71] 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.
  • 8Institut National de la Recherche Agronomique, Génétique Animale et Biologie Intégrative, F-78350 Jouy-en-Josas, France.
  • 9Institut National de la Recherche Agronomique, Domaine Expérimental du Pin au Haras, F-61310 Exmes, France.
  • 10Institute of Anatomy, Department Biomedicine, University of Basel, CH-4056 Basel, Switzerland.
  • 11Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.
  • 12Institut National de la Recherche Agronomique, Biométrie et Intelligence Artificielle, F-31326 Castanet-Tolosan, France.
  • 131] 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.
  • 141] Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland [2] Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland.
  • 15Institut Pasteur, Génétique Moléculaire de la Morphogenèse and Centre National de la Recherche Scientifique URA-2578, F-75015 Paris, France.
  • 161] 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.

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.

PMID:
24990743
[PubMed - indexed for MEDLINE]
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