Morphogenesis and cytodifferentiation of the avian retinal pigmented epithelium require downregulation of Group B1 Sox genes
Morphogenesis and cytodifferentiation of the avian retinal pigmented epithelium require downregulation of Group B1 Sox genes
复制标题
DOI：
10.1242/dev.031344
复制
发表时间：
2009-08-01
期刊：
影响因子：
4.6
通讯作者：
Mikawa, Takashi
中科院分区：
文献类型：
--
作者：
Ishii, Yasuo;Weinberg, Kerry;Mikawa, Takashi
视神经泡是视网膜的多能原基，可细分为神经视网膜和视网膜色素上皮域。尽管多种旁分泌因子在视神经泡形成中的作用已被广泛研究，但对于调节视网膜色素上皮的协调细胞形态发生和细胞分化的细胞自主机制知之甚少。在这里，我们证明 SoxB1 基因家族的成员 Sox1、Sox2 和 Sox3 在假定的视网膜色素上皮中均下调。在体内和体外假定的视网膜色素上皮中 SoxB1 表达的组成性维持导致立方形形态和色素沉着的缺失，并伴随神经分化标记物的诱导。我们还证明外源性 Fgf4 抑制假定视网膜色素上皮细胞中所有 SoxB1 家族成员的下调。这些结果表明，视网膜色素上皮形态发生和细胞分化需要 SoxB1 下调，这取决于是否暴露于 FGF 样信号。
The optic vesicle is a multipotential primordium of the retina, which becomes subdivided into the neural retina and retinal pigmented epithelium domains. Although the roles of several paracrine factors in patterning the optic vesicle have been studied extensively, little is known about cell-autonomous mechanisms that regulate coordinated cell morphogenesis and cytodifferentiation of the retinal pigmented epithelium. Here we demonstrate that members of the SoxB1 gene family, Sox1, Sox2 and Sox3, are all downregulated in the presumptive retinal pigmented epithelium. Constitutive maintenance of SoxB1 expression in the presumptive retinal pigmented epithelium both in vivo and in vitro resulted in the absence of cuboidal morphology and pigmentation, and in concomitant induction of neural differentiation markers. We also demonstrate that exogenous Fgf4 inhibits downregulation all SoxB1 family members in the presumptive retinal pigment epithelium. These results suggest that retinal pigment epithelium morphogenesis and cytodifferentiation requires SoxB1 downregulation, which depends on the absence of exposure to an FGF-like signal.