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24, chemin de Borde Rouge –Auzeville – CS52627
31326 Castanet Tolosan CEDEX - France

Dernière mise à jour : Mai 2018

Menu Logo Principal AgroParisTech Université Paris-Saclay


GABI : Génétique Animale et Biologie IntégrativeUnité Mixte de Recherche INRA - AgroParisTech

Evo-devo : Why cattle only have two toes

cattle in a prairie
During evolution of tetrapods, the organisation of the limbs of pentadactyls has often changed, reflecting a useful diversification through evolution. A study carried out in cattle in partnership with the Bale University and recently published in Nature, explored the genetic basis for the reduction of the number of limb buds, allowing an adaptation of this species during evolution.

Context and stakes

Like mice and men, primitive Artiodactyls (ungulates with an even number of limbs) had a pentadactyl skeleton. Progressively, the skeleton was modified, with both a decreased number of limbs and a lengthening of the existing ones, giving the Artiodactyls an evolutive advantage for running on differing terrains. Amongst them, cattle only have two rudimentary ergots and two symetric and elogated autopods.

To understand what molecular changes could be responsible for this adaptation, we undertook the study of the activity of the main genes that control limb development in mice and cattle.


The first stages of limb development in cattle are surprisingly similar to those in mice. The asymetry of gene expression is quickly lost in cattle and we were able to identify the cause.

Indeed, the regulation of the Ptch1 gene, which codes for the SHH (Sonic Headgehog) morphogen receptor, is specifically modified in the mesenchyme of the bovine limb-bud, due to a change in the cis-regulatory module of this gene.

This change has also been found in pigs, as confirmed by an American study, published in the same journal  (Cooper et al, 2014).


These studies show the remarkable plasticity of the mechanisms that preceded limb evolution.

The cow has proven to be an extremely original model, in addition to mice, for this evo-devo study.


Javier Lopez-Rios *, Amandine Duchesne *, Dario Speziale, Guillaume Andrey, Kevin A. Peterson, Philipp Germann, Erkan Ünal, Jing Liu, Sandrine Floriot, Sarah Barbey, Yves Gallard, Magdalena Müller-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. Attenuated sensing of SHH by Ptch1 underlies evolution of bovine limbs. Nature, 2014, 511 (7507): 46–51.

* Joint first authors