Visualization of spatiotemporal activation of Notch signaling: Live monitoring and significance in neural development
Visualization of spatiotemporal activation of Notch signaling: Live monitoring and significance in neural development
复制标题
DOI：
10.1016/j.ydbio.2005.08.003
复制
发表时间：
2005-10-01
影响因子：
2.7
通讯作者：
Okano, H
中科院分区：
文献类型：
--
作者：
Kohyama, J;Tokunaga, A;Okano, H
Notch信号在中枢神经系统发育过程中以环境依赖的方式在细胞命运决定中起着各种关键作用。然而，其确切的生理作用及其靶细胞的定位仍不清楚。为了解决这个问题，我们开发了一种新的报告系统，用于使用荧光蛋白Venus评估活细胞和组织中RBP-J介导的Notch信号转导靶基因的激活。我们的报告系统显示，Notch信号被选择性激活的神经球启动多能神经干细胞在体外和放射状胶质细胞在胚胎前脑在体内。此外，Notch信号的激活发生在胶质细胞生成期间，并且在星形胶质细胞发育的早期阶段是必需的。与这些发现一致，Notch信号的持续激活抑制GFAP阳性星形胶质细胞的分化。因此，我们的RBP-J依赖性活报告系统的开发，其在Notch激活时被激活，以及阶段依赖性功能获得分析，使我们能够进一步深入了解哺乳动物CNS发育中Notch信号传导的复杂性。(c)2005年爱思唯尔公司All rights reserved.
Notch signaling plays various key roles in cell fate determination during CNS development in a context-dependent fashion. However, its precise physiological role and the localization of its target cells remain unclear. To address this issue, we developed a new reporter system for assessing the RBP-J-mediated activation of Notch signaling target genes in living cells and tissues using a fluorescent protein Venus. Our reporter system revealed that Notch signaling is selectively activated in neurosphere-initiating multipotent neural stem cells in vitro and in radial glia in the embryonic forebrain in vivo. Furthermore, the activation of Notch signaling occurs during gliogenesis and is required in the early stage of astroglial development. Consistent with these findings, the persistent activation of Notch signaling inhibits the differentiation of GFAP-positive astrocytes. Thus, the development of our RBP-J-dependent live reporter system, which is activated upon Notch activation, together with a stage-dependent gain-of-function analysis allowed us to gain further insight into the complexity of Notch signaling in mammalian CNS development. (c) 2005 Elsevier Inc. All rights reserved.