Department of Biology and Chemistry, City University of Hong Kong, Kowloon, Hong Kong, China.
Dev Dyn. 2010 Dec;239(12):3204-14. doi: 10.1002/dvdy.22462.
In animal retina, hedgehog expression drives waves of neurogenesis, but genetic programs that control its expression during retinal neurogenesis are poorly elucidated. We have previously reported that irx1a is required for propagation of the sonic hedgehog (shh) expression waves in developing zebrafish retina. Here, we found that irx2a is expressed in the developing retina and that knockdown of irx2a results in a retinal phenotype strikingly similar to that of irx1a morphants. The expression of irx2a in retina ganglion cells was shown to be irx1a- and ath5-dependent suggesting that irx1a and ath5 are transcriptional regulators of irx2a. Furthermore, irx2a expression could rescue impaired propagation of shh waves in irx1a morphants. Together, these observations suggest that Irx2 functions downstream of irx1a to control shh expression in the retina. We proposed a novel transcriptional cascade of ath5-irx1a-irx2a in the regulation of hedgehog waves during vertebrate retinal development.
在动物视网膜中，刺猬表达驱动神经发生波，但控制其在视网膜神经发生过程中表达的遗传程序尚未得到充分阐明。我们之前曾报道过，irx1a 是斑马鱼视网膜中 sonic hedgehog (shh) 表达波传播所必需的。在这里，我们发现 irx2a 在发育中的视网膜中表达，irx2a 的敲低导致与 irx1a 形态发生体的视网膜表型惊人地相似。irx2a 在视网膜神经节细胞中的表达显示依赖于 irx1a 和 ath5，表明 irx1a 和 ath5 是 irx2a 的转录调节剂。此外，irx2a 的表达可以挽救 irx1a 形态发生体中 shh 波传播受损。综上所述，这些观察结果表明 Irx2 作为 irx1a 的下游因子，在控制视网膜中 shh 的表达。我们提出了一个在脊椎动物视网膜发育过程中 hedgehog 波调节中 ath5-irx1a-irx2a 的新转录级联。
