Attenuated sensing of SHH by Ptch1 underlies evolution of bovine limbs
Javier Lopez-Rios
(1)
,
Amandine Duchesne
(2, 1)
,
Dario Speziale
(1)
,
Guillaume Andrey
(3)
,
Kevin A Peterson
(4)
,
Philipp Germann
(5)
,
Erkan Unal
(1, 5)
,
Jing Liu
(4)
,
Sandrine Floriot
(2)
,
Sarah Barbey
(6)
,
Yves Gallard
(6)
,
Magdalena Müller-Gerbl
(7)
,
Andrew D Courtney
(8)
,
Christophe Klopp
(9)
,
Sabrina Rodriguez
(10, 2)
,
Robert Ivanek
(11, 12)
,
Christian Beisel
(5)
,
Carol Wicking
(8)
,
Dagmar Iber
(5)
,
Benoit Robert
(13)
,
Andrew P. Mcmahon
(4)
,
Denis Duboule
(14)
,
Rolf Zeller
(1)
1
Developmental Genetics, Department Biomedicine
2 GABI - Génétique Animale et Biologie Intégrative
3 School of Life Sciences
4 Keck School of Medicine [Los Angeles]
5 D-BSSE - Department of Biosystems Science and Engineering [ETH Zürich]
6 DEP - Domaine Expérimental du Pin
7 Institute of Anatomy, Department Biomedicine
8 Institute for Molecular Bioscience
9 UBIA - Unité de Biométrie et Intelligence Artificielle (ancêtre de MIAT)
10 LISBP - Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés
11 Developmental Genetics, Department Biomedicine
12 SIB - Swiss Institute of Bioinformatics [Lausanne]
13 Génétique Moléculaire de la Morphogénèse
14 Department of Genetics and Evolution
2 GABI - Génétique Animale et Biologie Intégrative
3 School of Life Sciences
4 Keck School of Medicine [Los Angeles]
5 D-BSSE - Department of Biosystems Science and Engineering [ETH Zürich]
6 DEP - Domaine Expérimental du Pin
7 Institute of Anatomy, Department Biomedicine
8 Institute for Molecular Bioscience
9 UBIA - Unité de Biométrie et Intelligence Artificielle (ancêtre de MIAT)
10 LISBP - Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés
11 Developmental Genetics, Department Biomedicine
12 SIB - Swiss Institute of Bioinformatics [Lausanne]
13 Génétique Moléculaire de la Morphogénèse
14 Department of Genetics and Evolution
Javier Lopez-Rios
- Fonction : Auteur
- PersonId : 774865
- ORCID : 0000-0001-6731-3798
Amandine Duchesne
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- Fonction : Auteur correspondant
- PersonId : 744260
- IdHAL : amandine-duchesne
- ORCID : 0000-0002-9713-2274
- IdRef : 113847246
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Jing Liu
- Fonction : Auteur
- PersonId : 759117
- ORCID : 0000-0002-8290-3494
Sandrine Floriot
- Fonction : Auteur
- PersonId : 744473
- IdHAL : sandrine-floriot
- ORCID : 0000-0001-9936-5621
Christophe Klopp
- Fonction : Auteur
- PersonId : 735911
- IdHAL : 0000-0001-7126-5477
- ORCID : 0000-0001-7126-5477
Sabrina Rodriguez
- Fonction : Auteur
- PersonId : 1205148
- IdHAL : sabrina-legoueix
Résumé
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.