Lee Hae Young, Wroblewski Emily, Philips Gary T, Stair Carrie N, Conley Kevin, Reedy Meredith, Mastick Grant S, Brown Nadean L
Department of Pediatrics, Northwestern University Medical School at Children's Memorial Institute for Education and Research, Chicago, IL 60614, USA.
Dev Biol. 2005 Aug 15;284(2):464-78. doi: 10.1016/j.ydbio.2005.06.010.
During embryogenesis, multiple developmental processes are integrated through their precise temporal regulation. Hes1 is a transcriptional repressor that regulates the timing of mammalian retinal neurogenesis. However, roles for Hes1 in early eye development have not been well defined. Here, we show that Hes1 is expressed in the forming lens, optic vesicle, cup, and pigmented epithelium and is necessary for proper growth, morphogenesis, and differentiation of these tissues. Because Hes1 is required throughout the eye, we investigated its interaction with Pax6. Hes1-Pax6 double mutant embryos are eyeless suggesting these genes are coordinately required for initial morphogenesis and outgrowth of the optic vesicle. In Hes1 mutants, Math5 expression is precocious along with retinal ganglion cell, amacrine, and horizontal neuron formation. In contrast to apparent cooperativity between Pax6 and Hes1 during morphogenesis, each gene regulates Math5 and RGC genesis independently. Together, these studies demonstrate that Hes1, like Pax6, simultaneously regulates multiple developmental processes during optic development.
在胚胎发生过程中，多个发育过程通过其精确的时间调控得以整合。Hes1是一种转录抑制因子，可调节哺乳动物视网膜神经发生的时间。然而，Hes1在早期眼睛发育中的作用尚未明确界定。在此，我们表明Hes1在形成中的晶状体、视泡、视杯和色素上皮中表达，并且对于这些组织的正常生长、形态发生和分化是必需的。由于整个眼睛都需要Hes1，我们研究了它与Pax6的相互作用。Hes1-Pax6双突变胚胎没有眼睛，这表明这些基因对于视泡的初始形态发生和生长是协同必需的。在Hes1突变体中，Math5的表达早熟，同时伴有视网膜神经节细胞、无长突细胞和水平神经元的形成。与形态发生过程中Pax6和Hes1之间明显的协同作用相反，每个基因独立调节Math5和视网膜神经节细胞的发生。总之，这些研究表明，与Pax6一样，Hes1在视神经发育过程中同时调节多个发育过程。
