Integrative Analyis of Vertebrate Retinal Lamination

脊椎动物视网膜分层的综合分析

• 批准号: 9212146
• 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 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9212146
• 关键词: Address; Adult; Affect; Apical; Attention; Binding; Cell Cycle Regulation; Cell physiology; Cells; Choroid; Data; Development; Endocytosis; 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; experimental study; improved; loss of function; mutant; neurogenesis; notch protein; photoreceptor degeneration; prevent; protein transport; public health relevance; retinal neuron; retinal progenitor cell; retinogenesis; tool; trafficking

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.

描述（由申请人提供）：综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。利用斑马鱼，我们开发了一系列转基因和突变工具来探索Notch和Hippo-Yap/Taz这两个对正常视网膜发育重要的通路之间的调节和关系。我们将研究单个细胞过程，特别是内吞作用和内膜运输，如何塑造这些途径。我们将把注意力放在每个通路的组成部分以及已经被证明可以调节Notch和hippop - yap /Taz的crumb上。除了评估通路调控的细微差别外，我们还将测试每个信号模块在视网膜形成中的精确功能。最后，我们讨论了面包屑介导的Hippo-Yap/Taz-Tead信号在光感受器稳态中的作用。提出的实验解决了Notch和Hippo/Yap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光感受器变性的靶标具有重要意义。

项目成果

Actomyosin is the main driver of interkinetic nuclear migration in the retina.

• DOI: 10.1016/j.cell.2009.06.032
• 发表时间: 2009-09-18
• 期刊: Cell
• 影响因子: 64.5
• 作者: Norden C;Young S;Link BA;Harris WA
• 通讯作者: Harris WA

Cell biological regulation of division fate in vertebrate neuroepithelial cells.

• DOI: 10.1002/dvdy.22684
• 发表时间: 2011-08
• 期刊: DEVELOPMENTAL DYNAMICS
• 影响因子: 2.5
• 作者: Willardsen, Minde I.;Link, Brian A.
• 通讯作者: Link, Brian A.