I3S, Institute for Innovation and Health Research, University of Porto, Porto, Portugal.
Cell Growth and Differentiation Group, IBMC/I3S, Rua Alfredo Allen 208, 4200-135, Porto, Portugal.
Sci Rep. 2021 Mar 30;11(1):7165. doi: 10.1038/s41598-021-86621-4.
The overexpression of hoxd13a during zebrafish fin development causes distal endochondral expansion and simultaneous reduction of the finfold, mimicking the major events thought to have happened during the fin-to-limb transition in Vertebrates. We investigated the effect of hoxd13a overexpression on putative downstream targets and found it to cause downregulation of proximal fin identity markers (meis1 and emx2) and upregulation of genes involved in skeletogenesis/patterning (fbn1, dacha) and AER/Finfold maintenance (bmps). We then show that bmp2b overexpression leads to finfold reduction, recapitulating the phenotype observed in hoxd13a-overexpressing fins. In addition, we show that during the development of the long finfold in leo/lof mutants, hoxd13a and bmp2b are downregulated. Our results suggest that modulation of the transcription factor Hoxd13 during evolution may have been involved in finfold reduction through regulation of the Bmp signalling that then activated apoptotic mechanisms impairing finfold elongation.
在斑马鱼鳍发育过程中，hoxd13a 的过表达导致远端软骨外生扩张，同时鳍褶减小，模拟了在脊椎动物鳍到肢的过渡过程中被认为发生的主要事件。我们研究了 hoxd13a 过表达对潜在下游靶标的影响，发现它导致近端鳍身份标记（meis1 和 emx2）下调，以及参与骨骼发生/模式形成（fbn1、dacha）和 AER/鳍褶维持（bmps）的基因上调。然后，我们表明 bmp2b 的过表达导致鳍褶减小，再现了在 hoxd13a 过表达的鳍中观察到的表型。此外，我们表明在 leo/lof 突变体中长鳍褶的发育过程中，hoxd13a 和 bmp2b 下调。我们的结果表明，转录因子 Hoxd13 在进化过程中的调节可能通过调节 Bmp 信号通路参与了鳍褶的减小，从而激活了凋亡机制，损害了鳍褶的伸长。
