Attenuated sensing of SHH by Ptch1 underlies evolution of bovine limbs

被引:95
作者
Lopez-Rios, Javier [1 ]
Duchesne, Amandine [1 ,2 ]
Speziale, Dario [1 ]
Andrey, Guillaume [3 ]
Peterson, Kevin A. [4 ]
Germann, Philipp [5 ,6 ]
Uenal, Erkan [1 ,5 ,6 ]
Liu, Jing [4 ]
Floriot, Sandrine [2 ]
Barbey, Sarah [7 ]
Gallard, Yves [7 ]
Mueller-Gerbl, Magdalena [8 ]
Courtney, Andrew D. [9 ]
Klopp, Christophe [10 ]
Rodriguez, Sabrina [2 ]
Ivanek, Robert [1 ,6 ]
Beisel, Christian [5 ,6 ]
Wicking, Carol [9 ]
Iber, Dagmar [5 ,6 ]
Robert, Benoit [11 ,12 ]
McMahon, Andrew P. [4 ]
Duboule, Denis [3 ,13 ]
Zeller, Rolf [1 ]
机构
[1] Univ Basel, Dept Biomed, CH-4058 Basel, Switzerland
[2] INRA, Genet Anim & Biol Integrat, F-78350 Jouy En Josas, France
[3] Fed Inst Technol Lausanne, Sch Life Sci, CH-1015 Lausanne, Switzerland
[4] Univ So Calif, Keck Sch Med, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Dept Stem Cell Biol & Regenerat Med, Los Angeles, CA 90089 USA
[5] Fed Inst Technol Zurich, Dept Biosyst Sci & Engn, CH-4058 Basel, Switzerland
[6] Swiss Inst Bioinformat, CH-4058 Basel, Switzerland
[7] INRA, Domaine Expt Pin Haras, F-61310 Exmes, France
[8] Univ Basel, Dept Biomed, Inst Anat, CH-4056 Basel, Switzerland
[9] Univ Queensland, Inst Mol Biosci, St Lucia, Qld 4072, Australia
[10] INRA, Biometrie & Intelligence Artificielle, F-31326 Castanet Tolosan, France
[11] Inst Pasteur, F-75015 Paris, France
[12] CNRS, URA 2578, F-75015 Paris, France
[13] Univ Geneva, Dept Genet & Evolut, CH-1211 Geneva, Switzerland
基金
英国医学研究理事会;
关键词
GENE REGULATORY NETWORKS; SONIC-HEDGEHOG; BAC LIBRARY; DEVELOPMENTAL BASIS; DIGIT NUMBER; EXPRESSION; CONSTRUCTION; RANGE; MORPHOGEN; REDUCTION;
D O I
10.1038/nature13289
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:46 / +
页数:16
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