Nel positively regulates the genesis of retinal ganglion cells by promoting their differentiation and survival during development.
Nel positively regulates the genesis of retinal ganglion cells by promoting their differentiation and survival during development.
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DOI：
10.1091/mbc.e13-08-0453
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发表时间：
2014-01
影响因子：
3.3
通讯作者：
Nakamoto M
中科院分区：
文献类型：
--
作者：
Nakamoto C;Kuan SL;Findlay AS;Durward E;Ouyang Z;Zakrzewska ED;Endo T;Nakamoto M
Nel是一种血小板反应蛋白-1样细胞外糖蛋白，主要在脊椎动物神经系统中表达。它通过促进视网膜神经节细胞（RGCs）在发育过程中的分化和存活来刺激其发生，是产生适量RGCs的必要条件。为了神经系统的正常运作，在发育过程中必须产生适当数量和补充的神经元细胞类型。然而，调控单个神经元种类产生的分子机制尚不清楚。在这项研究中，我们研究了血小板反应蛋白-1样糖蛋白Nel（神经表皮生长因子[EGF]样）在小鸡视网膜神经节细胞（RGCs）生成中的功能。在眼睛发育过程中，Nel在视网膜色素上皮和RGCs中强烈表达。通过卵内电穿孔在发育中的视网膜中过度表达Nel增加了RGCs的数量，而移位的无突细胞的数量减少。相反，通过转座子介导的RNA干扰构建物敲低Nel表达，可导致RGC数量减少，无毛细胞移位数量增加。Nel表达水平的改变似乎不影响视网膜祖细胞的增殖，但它们显著改变了RGC从中央视网膜向周围视网膜分化的进展速度。此外，Nel在视网膜发育过程中保护RGCs免于凋亡。这些结果表明，在发育过程中，Nel通过促进RGC的分化和存活，积极调节RGC的产生。
Nel is a thrombospondin-1–like extracellular glycoprotein that is predominantly expressed in the vertebrate nervous system. It stimulates the genesis of retinal ganglion cells (RGCs) by promoting their differentiation and survival during development and is essential for production of proper numbers of RGCs. For correct functioning of the nervous system, the appropriate number and complement of neuronal cell types must be produced during development. However, the molecular mechanisms that regulate the production of individual classes of neurons are poorly understood. In this study, we investigate the function of the thrombospondin-1–like glycoprotein, Nel (neural epidermal growth factor [EGF]-like), in the generation of retinal ganglion cells (RGCs) in chicks. During eye development, Nel is strongly expressed in the presumptive retinal pigment epithelium and RGCs. Nel overexpression in the developing retina by in ovo electroporation increases the number of RGCs, whereas the number of displaced amacrine cells decreases. Conversely, knockdown of Nel expression by transposon-mediated introduction of RNA interference constructs results in decrease in RGC number and increase in the number of displaced amacrine cells. Modifications of Nel expression levels do not appear to affect proliferation of retinal progenitor cells, but they significantly alter the progression rate of RGC differentiation from the central retina to the periphery. Furthermore, Nel protects RGCs from apoptosis during retinal development. These results indicate that Nel positively regulates RGC production by promoting their differentiation and survival during development.