Attenuated sensing of SHH by Ptch1 underlies evolution of bovine limbs

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 in:
NATURE, 511, 7507, 46-U553
London, Nature Publishing Group
Lopez-Rios, Javier Duchesne, Amandine Speziale, Dario Andrey, Guillaume 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 eng NS 033642/NS/NINDS NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. England 2014/07/06 06:00 Nature. 2014 Jul 3;511(7507):46-51. doi: 10.1038/nature13289. Epub 2014 Jun 18.

 Record created 2014-08-07, last modified 2018-12-03

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