Integrative Analyis of Vertebrate Retinal Lamination

脊椎动物视网膜分层的综合分析

• 批准号: 8638317
• 负责人: Brian A Link
• 金额: $ 38.25万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-01 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8638317
• 关键词: Address; Adult; Affect; Apical; Attention; Binding; Cell Cycle Regulation; Cell physiology; Cells; Choroid; Data; Development; Endocytosis; Figs - dietary; Funding; Genetic; Goals; Homeostasis; Human; Individual; Maintenance; Mediating; Modification; Mutation; Nature; Neurons; Nuclear; Pathway interactions; Pattern; Phenotype; Photoreceptors; Positioning Attribute; Regulation; Research; Retina; Retinal; Role; Series; Shapes; Signal Pathway; Signal Transduction; Stem cells; Structure of retinal pigment epithelium; System; Testing; Tissues; Transgenic Organisms; Zebrafish; base; improved; loss of function; mutant; neuroepithelium; neurogenesis; notch protein; photoreceptor degeneration; prevent; protein transport; public health relevance; research study; retinal neuron; retinal progenitor cell; retinogenesis; tool; trafficking

ABSTRACT 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 a 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 a better defining targets for slowing or preventing photoreceptor degenerations. !

摘要 整合信号在视网膜发育和成熟神经元的维持中都是至关重要的。使用 斑马鱼，我们已经开发了一系列的转基因和突变的工具，以探讨调控和关系 两个重要的途径之间的正常视网膜发育，Notch和Hippo-Yap/Taz。我们将 研究单个细胞过程，特别是内吞作用和内膜运输， 这些途径。注意力将放在每个途径的组成部分，以及一个面包屑，这已经被 所示为调谐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在视网膜发生中的精确功能。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拟议的实验 解决Notch和Hippo/雅普信号传导的本质的基本细胞问题。因此，这项研究 对改善干细胞操作和更好地定义减缓或预防 光感受器退化。 !