通过音猬因子和HOXD增强子的模块化进化实现蛇类腿部的丢失与重新出现

Loss and Re-emergence of Legs in Snakes by Modular Evolution of Sonic hedgehog and HOXD Enhancers.

作者信息

Leal Francisca, Cohn Martin J

机构信息

Howard Hughes Medical Institute, UF Genetics Institute, University of Florida, P.O. Box 103610, University of Florida, Gainesville, FL 32610, USA; Department of Biology, UF Genetics Institute, University of Florida, P.O. Box 103610, University of Florida, Gainesville, FL 32610, USA; Department of Molecular Genetics and Microbiology, UF Genetics Institute, University of Florida, P.O. Box 103610, University of Florida, Gainesville, FL 32610, USA.

出版信息

Curr Biol. 2016 Nov 7;26(21):2966-2973. doi: 10.1016/j.cub.2016.09.020. Epub 2016 Oct 20.

DOI:10.1016/j.cub.2016.09.020

PMID:27773569

Abstract

Limb reduction and loss are hallmarks of snake evolution. Although advanced snakes are completely limbless, basal and intermediate snakes retain pelvic girdles and small rudiments of the femur. Moreover, legs may have re-emerged in extinct snake lineages [1-5], suggesting that the mechanisms of limb development were not completely lost in snakes. Here we report that hindlimb development arrests in python embryos as a result of mutations that abolish essential transcription factor binding sites in the limb-specific enhancer of Sonic hedgehog (SHH). Consequently, SHH transcription is weak and transient in python hindlimb buds, leading to early termination of a genetic circuit that drives limb outgrowth. Our results suggest that degenerate evolution of the SHH limb enhancer played a role in reduction of hindlimbs during snake evolution. By contrast, HOXD digit enhancers are conserved in pythons, and HOXD gene expression in the hindlimb buds progresses to the distal phase, forming an autopodial (digit) domain. Python hindlimb buds then develop transitory pre-chondrogenic condensations of the tibia, fibula, and footplate, raising the possibility that re-emergence of hindlimbs during snake evolution did not require de novo re-evolution of lost structures but instead could have resulted from persistence of embryonic legs. VIDEO ABSTRACT.

摘要

肢体减少和缺失是蛇类进化的标志。尽管高等蛇类完全没有四肢，但基干蛇类和中间过渡型蛇类仍保留着骨盆带和微小的股骨残迹。此外，在已灭绝的蛇类谱系中，腿部可能曾再次出现[1 - 5]，这表明肢体发育机制在蛇类中并未完全丧失。在此，我们报告说，由于突变消除了音猬因子（SHH）肢体特异性增强子中必需的转录因子结合位点，蟒胚胎的后肢发育停滞。因此，SHH转录在蟒后肢芽中微弱且短暂，导致驱动肢体生长的遗传回路提前终止。我们的结果表明，SHH肢体增强子的退化进化在蛇类进化过程中后肢的减少中发挥了作用。相比之下，HOXD指增强子在蟒中是保守的，并且后肢芽中HOXD基因的表达进展到远端阶段，形成一个自足（指）域。蟒的后肢芽随后会发育出胫骨、腓骨和足板的短暂软骨前凝聚，这增加了蛇类进化过程中后肢再次出现并非需要重新从头进化已丢失结构，而是可能源于胚胎腿部持续存在的可能性。视频摘要。