脊椎动物附肢发育及进化机制的研究进展

Advances in vertebrate appendage development and its evolutionary mechanism

动物形态的多样性造就了丰富多彩的动物世界.脊椎动物附肢形态的发生一直以来是研究物种形态进化发育的典型例子.脊椎动物的附肢在漫长的进化历程中发生了多次重大的改变,这大大提高了脊椎动物的适应性.另外,在由水生鳍向陆生足演化以及四足动物形态各异的四肢发育过程中,涉及很多与发育相关的基因和调控通路.本文结合发育生物学和遗传学的证据,综述了近年来对脊椎动物四肢发育及进化机制的相关研究,强调了基因的时空差异表达及调控是造成生物形态适应性进化的主要驱动力.

Vertebrates display a vast array of morphological adaptations to ecological niches. These involve multiple large-scale changes of the appendages, such as evolving limbs from fins, wings （birds, bats）, and even the loss of appendages （caecilians, lizards, snakes） during the transition from water to land. Reversals also exist, such as whales evolving back to having fins. This tremendous diversity of appendages leads to development of vertebrate appendage being a model for understanding the evolution and development of appendage morphologies. The development of appendages from buds is conserved among vertebrate. Appendage growth depends on cell proliferation and specializations along proximal-distal （PD）, anterior-posterior （AP） and dorsal-ventral （DV） axes. Cell proliferation in lateral plate mesoderm relates to the initiation of buds. The growth of ectodermal cells forms an apical ectodermal ridge along the bud and secreted fibroblast growth factors （Fgfs） control outgrowth of the bud. Gene expression in a specific time and region and levels of expression determines if a bud becomes a fin, wing or limb. Several genes and regulation signal pathways have evolved during transition of fins to alternative types of limbs. Fgfs, Wnts, Shh, RA and Bmps signaling regulate the genes Tbx5, Tbx4, Fgf8, and Bmp and the Hox gene family, respectively, which are essential for appendage development and evolution. These genes associate with chondrocyte proliferation and differentiation. T-box, fgfs and wnts in lateral plate mesoderm are essential for lateral bud initiation, which relates to the transition of ancestral median fins to paired fins. The origin of appendages for the emergence onto land was depended on regions and levels of expression for such as Bmp4, Hoxdl3 and hand2, which bmps and shh signals regulate, respectively. Hoxl3 is expressed on the distal margin of fins and limbs buds while the larger-scale region of expression in the limb bud constitutes the basis of the development of the PD axis in terrestrial vertebrates. Loss of Hand2 leads to the deficiency of hind-limbs in whales. High levels of expression of Bmps in the forelimb of bats lead the forelimb to be longer than the hind-one. Furthermore, not only signaling regulation, but also transcription factors, regions of genome regulation and some long non-coding RNAs （lncRNAs） play regulatory roles in gene expression during appendage development. In this paper, we review the advances in limb development and evolution via evidence from developmental biology and genetics. We highlight that differences in temporal and spatial expression gene regulation are the main driving forces for adaptive evolution and morphological variation. We emphasize that by combining evolutionary genomics, comparative genomics and transcriptome analyses, it is possible to reveal how vertebrate appendages evolved. To verify the drivers of morphological diversity, it is necessary to consider the complex interactions of the multiple genes involved in the evolution of development through time.