Attenuated Sensing of SHH by Ptch1 Underlies Evolution of Bovine Limbs

Overview

Journal Nature

Specialty Science

Date 2014 Jul 4

PMID 24990743

Citations 58

Authors

Javier Lopez-Rios

Amandine Duchesne

Dario Speziale

Guillaume Andrey

Kevin A Peterson

Philipp Germann

Erkan Unal

Jing Liu

Sandrine Floriot

Sarah Barbey

Yves Gallard

Magdalena Muller-Gerbl

Andrew D Courtney

Christophe Klopp

Sabrina Rodriguez

Robert Ivanek

Christian Beisel

Carol Wicking

Dagmar Iber

Benoit Robert

Andrew P McMahon

Denis Duboule

Rolf Zeller

Affiliations

Soon will be listed here.

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.

Citing Articles

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