Attenuated sensing of SHH by Ptch1 underlies evolution of bovine limbs

Javier Lopez-Rios¹, Amandine Duchesne², Dario Speziale³, Guillaume Andrey⁴, Kevin A Peterson⁵, Philipp Germann⁶, Erkan Unal⁷, Jing Liu⁵, Sandrine Floriot⁸, Sarah Barbey⁹, Yves Gallard⁹, Magdalena Müller-Gerbl¹⁰, Andrew D Courtney¹¹, Christophe Klopp¹², Sabrina Rodriguez¹³, Robert Ivanek¹⁴, Christian Beisel⁶, Carol Wicking¹¹, Dagmar Iber⁶, Benoit Robert¹⁵, Andrew P McMahon⁵, Denis Duboule¹⁶, Rolf Zeller³

Affiliations

¹ 1] Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland [2].
² 1] Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland [2] Institut National de la Recherche Agronomique, Génétique Animale et Biologie Intégrative, F-78350 Jouy-en-Josas, France [3].
³ Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland.
⁴ School of Life Sciences, Federal Institute of Technology Lausanne, CH-1015 Lausanne, Switzerland.
⁵ Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
⁶ Department for Biosystems Science and Engineering, Federal Institute of Technology Zurich and Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland.
⁷ 1] Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland [2] Department for Biosystems Science and Engineering, Federal Institute of Technology Zurich and Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland.
⁸ Institut National de la Recherche Agronomique, Génétique Animale et Biologie Intégrative, F-78350 Jouy-en-Josas, France.
⁹ Institut National de la Recherche Agronomique, Domaine Expérimental du Pin au Haras, F-61310 Exmes, France.
¹⁰ Institute of Anatomy, Department Biomedicine, University of Basel, CH-4056 Basel, Switzerland.
¹¹ Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.
¹² Institut National de la Recherche Agronomique, Biométrie et Intelligence Artificielle, F-31326 Castanet-Tolosan, France.
¹³ 1] Institut National de la Recherche Agronomique, Génétique Animale et Biologie Intégrative, F-78350 Jouy-en-Josas, France [2] Institut National de la Recherche Agronomique, Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés, F-31077 Toulouse, France.
¹⁴ 1] Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland [2] Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland.
¹⁵ Institut Pasteur, Génétique Moléculaire de la Morphogenèse and Centre National de la Recherche Scientifique URA-2578, F-75015 Paris, France.
¹⁶ 1] School of Life Sciences, Federal Institute of Technology Lausanne, CH-1015 Lausanne, Switzerland [2] Department of Genetics and Evolution, University of Geneva, CH-1211 Geneva, Switzerland.

PMID: 24990743
DOI: 10.1038/nature13289

Attenuated sensing of SHH by Ptch1 underlies evolution of bovine limbs

Javier Lopez-Rios et al. Nature. 2014.

. 2014 Jul 3;511(7507):46-51.

doi: 10.1038/nature13289. Epub 2014 Jun 18.

Authors

Affiliations

¹ 1] Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland [2].
² 1] Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland [2] Institut National de la Recherche Agronomique, Génétique Animale et Biologie Intégrative, F-78350 Jouy-en-Josas, France [3].
³ Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland.
⁴ School of Life Sciences, Federal Institute of Technology Lausanne, CH-1015 Lausanne, Switzerland.
⁵ Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
⁶ Department for Biosystems Science and Engineering, Federal Institute of Technology Zurich and Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland.
⁷ 1] Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland [2] Department for Biosystems Science and Engineering, Federal Institute of Technology Zurich and Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland.
⁸ Institut National de la Recherche Agronomique, Génétique Animale et Biologie Intégrative, F-78350 Jouy-en-Josas, France.
⁹ Institut National de la Recherche Agronomique, Domaine Expérimental du Pin au Haras, F-61310 Exmes, France.
¹⁰ Institute of Anatomy, Department Biomedicine, University of Basel, CH-4056 Basel, Switzerland.
¹¹ Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.
¹² Institut National de la Recherche Agronomique, Biométrie et Intelligence Artificielle, F-31326 Castanet-Tolosan, France.
¹³ 1] Institut National de la Recherche Agronomique, Génétique Animale et Biologie Intégrative, F-78350 Jouy-en-Josas, France [2] Institut National de la Recherche Agronomique, Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés, F-31077 Toulouse, France.
¹⁴ 1] Developmental Genetics, Department Biomedicine, University of Basel, CH-4058 Basel, Switzerland [2] Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland.
¹⁵ Institut Pasteur, Génétique Moléculaire de la Morphogenèse and Centre National de la Recherche Scientifique URA-2578, F-75015 Paris, France.
¹⁶ 1] School of Life Sciences, Federal Institute of Technology Lausanne, CH-1015 Lausanne, Switzerland [2] Department of Genetics and Evolution, University of Geneva, CH-1211 Geneva, Switzerland.

PMID: 24990743
DOI: 10.1038/nature13289

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.

PubMed Disclaimer

Comment in

Evolutionary developmental biology: Use it or lose it.
Huang BL, Mackem S. Huang BL, et al. Nature. 2014 Jul 3;511(7507):34-5. doi: 10.1038/nature13509. Epub 2014 Jun 18. Nature. 2014. PMID: 24990735 No abstract available.

References

1. Nat Methods. 2012 Oct;9(10):969-72 - PubMed
1. Bioinformatics. 2009 Jul 15;25(14):1754-60 - PubMed
1. Genes Dev. 2008 Jan 15;22(2):141-51 - PubMed
1. Dev Dyn. 2001 Oct;222(2):178-91 - PubMed
1. Science. 2002 Feb 1;295(5556):868-72 - PubMed

Publication types

Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions
Actions

Associated data

Actions
- Search in PubMed
- Search in GEO
Actions
- Search in PubMed
- Search in GEO

Grants and funding

LinkOut - more resources

Full Text Sources
- Nature Publishing Group
- Ovid Technologies, Inc.
Other Literature Sources
- scite Smart Citations
Molecular Biology Databases
- Mouse Genome Informatics (MGI)
- NIAID Data Ecosystem - Find datasets on Infectious and Immune-mediated Diseases

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Attenuated sensing of SHH by Ptch1 underlies evolution of bovine limbs

Affiliations

Attenuated sensing of SHH by Ptch1 underlies evolution of bovine limbs

Authors

Affiliations

Abstract

Comment in

References

Publication types

MeSH terms

Substances

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Molecular Biology Databases