Cadete Francisco, Francisco Miguel, Freitas Renata
I3S, Institute for Innovation and Health Research/University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal.
ICBAS, Institute of Biomedical Sciences Abel Salazar/University of Porto, Rua Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal.
Evolution. 2023 Apr 27;77(5):1262-1271. doi: 10.1093/evolut/qpad043.
In tetrapods, BMP-signaling coordinates limb outgrowth, skeleton patterning, and apoptosis during the formation of their typical autopod structures, the digits. In addition, inhibition of BMP signaling during mouse limb development leads to the persistence and enlargement of an important signaling center, the apical ectodermal ridge (AER), and consequent digit defects. Interestingly, during fish fin development there is a natural elongation of the AER, rapidly converted into an apical finfold (FF), in which osteoblasts differentiate into dermal fin-rays used in aquatic locomotion. Previous reports have led us to suggest that upregulation of Hox13 genes in the distal fin mesenchyme, caused by the origin of novel enhancer modules, may have caused an increment of the BMP signaling potentially leading to the apoptosis of these osteoblasts precursors of the fin-rays. To explore this hypothesis, we characterized the expression of several components of the BMP signaling in zebrafish lines with distinct FF sizes (bmp2b, smad1, smoc1, smoc2, grem1a, msx1b, msx2b, Psamd1/5/9). Our data suggest that the BMP signaling is enhanced in shorter FFs and inhibited in longer FFs, as implied by the differential expression of several components of this network. In addition, we detected an earlier expression of several of these BMP-signaling components associated with the development of short FFs and the opposite tendency during the development of longer FFs. Thus, our results suggest that a heterochronic shift, involving enhanced Hox13 expression and BMP signaling may have caused the reduction of the FF size during the evolutionary transition from fish fins to tetrapod limbs.
在四足动物中，骨形态发生蛋白（BMP）信号在其典型的 autopod 结构（即指）形成过程中协调肢体生长、骨骼模式形成和细胞凋亡。此外，在小鼠肢体发育过程中抑制 BMP 信号会导致一个重要信号中心——顶端外胚层嵴（AER）持续存在并扩大，进而导致指缺陷。有趣的是，在鱼类鳍发育过程中，AER 会自然延长，并迅速转变为顶端鳍褶（FF），其中成骨细胞分化为用于水生运动的真皮鳍条。先前的报道使我们推测，新增强子模块的起源导致远端鳍间充质中 Hox13 基因上调，这可能导致 BMP 信号增加，从而可能导致鳍条成骨细胞前体凋亡。为了探究这一假设，我们在具有不同 FF 大小的斑马鱼品系中（bmp2b、smad1、smoc1、smoc2、grem1a、msx1b、msx2b、Psamd1/5/9）对 BMP 信号的几个组成部分的表达进行了表征。我们的数据表明，如该网络几个组成部分的差异表达所暗示的那样，BMP 信号在较短的 FF 中增强，而在较长的 FF 中受到抑制。此外，我们检测到其中几个 BMP 信号组成部分在短 FF 发育过程中更早表达，而在长 FF 发育过程中则呈现相反趋势。因此，我们的结果表明，涉及 Hox13 表达增强和 BMP 信号的异时性转变可能在从鱼鳍到四足动物肢体的进化转变过程中导致了 FF 大小的减小。
