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Attenuated sensing of SHH by Ptch1 underlies evolution of bovine limbs

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

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Official URL: https://edoc.unibas.ch/62382/

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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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Anatomy > Developmental Genetics (Zeller/Zuniga)
03 Faculty of Medicine > Departement Biomedizin > Division of Anatomy > Musculosceletal Research (Müller-Gerbl)
UniBasel Contributors:Müller-Gerbl, Magdalena and Zeller, Rolf
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Macmillan
ISSN:0028-0836
e-ISSN:1476-4687
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:04 Aug 2020 11:37
Deposited On:04 Aug 2020 11:37

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