Furimsky Marosh, Wallace Valerie A
Molecular Medicine Program, Ottawa Health Research Institute and University of Ottawa Eye Institute, Ottawa, Ontario, Canada.
Dev Dyn. 2006 Mar;235(3):594-605. doi: 10.1002/dvdy.20658.
The Sonic hedgehog (Shh) signaling pathway plays a key role in the development of the vertebrate central nervous system, including the eye. This pathway is mediated by the Gli transcription factors (Gli1, Gli2, and Gli3) that differentially activate and repress the expression of specific downstream target genes. In this study, we investigated the roles of the three vertebrate Glis in mediating midline Shh signaling in early ocular development. We examined the ocular phenotypes of Shh and Gli combination mutant mouse embryos and monitored proximodistal and dorsoventral patterning by the expression of specific eye development regulatory genes using in situ hybridization. We show that midline Shh signaling relieves the repressor activity of Gli3 adjacent to the midline and then promotes eye pattern formation through the nonredundant activities of all three Gli proteins. Gli3, in particular, is required to specify the dorsal optic stalk and to define the boundary between the optic stalk and the optic cup.
音猬因子（Shh）信号通路在脊椎动物中枢神经系统（包括眼睛）的发育中起关键作用。该通路由Gli转录因子（Gli1、Gli2和Gli3）介导，这些转录因子差异激活和抑制特定下游靶基因的表达。在本研究中，我们研究了三种脊椎动物Gli蛋白在早期眼部发育中介导中线Shh信号的作用。我们检查了Shh和Gli组合突变小鼠胚胎的眼部表型，并通过原位杂交使用特定的眼睛发育调控基因的表达来监测近远轴和背腹轴模式形成。我们发现中线Shh信号解除了中线附近Gli3的抑制活性，然后通过所有三种Gli蛋白的非冗余活性促进眼睛模式形成。特别是，Gli3是确定背侧视神经柄和定义视神经柄与视杯之间边界所必需的。
