Attenuated sensing of SHH by Ptch1 underlies evolution of bovine limbs

Lopez-Rios, Javier, Duchesne, Amandine, Speziale, Dario, Peterson, Kevin A., Germann, Philipp, Unal, Erkan, Liu, Jing, Floriot, Sandrine, Barbey, Sarah, Gallard, Yves, Muller-Gerbl, Magdalena, Courtney, Andrew D., Klopp, Christophe, Rodriguez, Sabrina, Ivanek, Robert, Beisel, Christian, Wicking, Carol, Iber, Dagmar, Robert, Benoit, McMahon, Andrew P., Duboule, Denis and Zeller, Rolf (2014) Attenuated sensing of SHH by Ptch1 underlies evolution of bovine limbs. Nature, 511 7507: 46-51. doi:10.1038/nature13289

Author Lopez-Rios, Javier
Duchesne, Amandine
Speziale, Dario
Peterson, Kevin A.
Germann, Philipp
Unal, Erkan
Liu, Jing
Floriot, Sandrine
Barbey, Sarah
Gallard, Yves
Muller-Gerbl, Magdalena
Courtney, Andrew D.
Klopp, Christophe
Rodriguez, Sabrina
Ivanek, Robert
Beisel, Christian
Wicking, Carol
Iber, Dagmar
Robert, Benoit
McMahon, Andrew P.
Duboule, Denis
Zeller, Rolf
Title Attenuated sensing of SHH by Ptch1 underlies evolution of bovine limbs
Journal name Nature   Check publisher's open access policy
ISSN 0028-0836
Publication date 2014-01-01
Year available 2014
Sub-type Article (original research)
DOI 10.1038/nature13289
Open Access Status Not yet assessed
Volume 511
Issue 7507
Start page 46
End page 51
Total pages 6
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 1000 General
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.
Keyword Multidisciplinary Sciences
Science & Technology - Other Topics
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 31003A_130803/146248
NS 033642
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 36 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 40 times in Scopus Article | Citations
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