Integrative Analyis of Vertebrate Retinal Lamination

描述（由申请人提供）：整合信号在视网膜发育和成熟神经元的维持过程中都至关重要。利用斑马鱼，我们已经开发了一系列转基因和突变体工具来探测对正常视网膜发育重要的两个途径Notch和Hippo-Yap/Taz之间的调节和关系。我们将研究如何个别细胞过程，特别是内吞作用和内膜运输，塑造这些途径。注意力将放在每个途径的组成部分以及Crumbs上，Crumbs已被证明可以调节Notch和Hippo-Yap/Taz。除了评估通路调节的细微差别，我们还将测试每个信号模块对视网膜发生的精确功能。最后，我们讨论了Crumbs介导的Hippo-Yap/Taz-Tead信号在光感受器稳态中的作用。所提出的实验解决了Notch和Hippo/雅普信号传导性质的基本细胞问题。因此，这项研究对改善干细胞操作和更好地确定减缓或预防感光细胞变性的目标具有意义。

DESCRIPTION (provided by applicant): Integrated signaling is critical both during retinal development and in maintenance of mature neurons. Using zebrafish, we have developed a series of transgenic and mutant tools to probe the regulation and relationships between two pathways important for normal retinal development, Notch and Hippo-Yap/Taz. We will investigate how individual cellular processes, particularly endocytosis and endomembrane trafficking, shape these pathways. Attention will be placed on components of each pathway as well as Crumbs, which has been shown to tune both Notch and Hippo-Yap/Taz. In addition to assessing the nuances of pathway regulation, we will also test the precise function of each signaling module on retinogenesis. Last, we address the function of Crumbs mediated Hippo-Yap/Taz-Tead signaling in photoreceptor homeostasis. The proposed experiments address basic cellular questions on the nature of Notch and Hippo/Yap signaling. This research, therefore, has implications for improving stem cell manipulation and better defining targets for slowing or preventing photoreceptor degenerations.