Nelson Branden R, Gumuscu Burak, Hartman Byron H, Reh Thomas A
Department of Biological Structure, University of Washington, Seattle, WA 98195, USA.
Dev Neurosci. 2006;28(1-2):128-41. doi: 10.1159/000090759.
The Notch signaling pathway is important at several stages of retinal development including the differentiation of retinal ganglion cells and Muller glia. The downstream effectors of Notch signaling, Hes1 and Hes5, have been shown to be critical in the retina as well. While Notch activity directly regulates Hes1 and Hes5 elsewhere in the nervous system, it has been unclear whether Hes1 and/or Hes5 are directly regulated by Notch activity in the developing retina. Here, we report that both Hes1 and Hes5 are directly regulated by Notch activity during retinal development. Using fluorescence-based Hes1 and Hes5 reporter constructs, we can monitor Notch activity in progenitor cells in the intact retina, and we find that Notch activity is downregulated just prior to retinal ganglion cell differentiation.
Notch信号通路在视网膜发育的几个阶段都很重要，包括视网膜神经节细胞和穆勒胶质细胞的分化。Notch信号通路的下游效应分子Hes1和Hes5在视网膜中也被证明至关重要。虽然Notch活性在神经系统的其他部位直接调节Hes1和Hes5，但在发育中的视网膜中，Hes1和/或Hes5是否直接受Notch活性调节尚不清楚。在此，我们报告在视网膜发育过程中，Hes1和Hes5均直接受Notch活性调节。使用基于荧光的Hes1和Hes5报告基因构建体，我们可以监测完整视网膜中祖细胞的Notch活性，并且我们发现就在视网膜神经节细胞分化之前，Notch活性被下调。
