Development of retinofugal parallel pathways

视网膜脱离平行通路的发展

• 批准号: 8411123
• 负责人: Andrew D Huberman
• 金额: $ 35.92万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-01 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8411123
• 关键词: Axon; Brain; Cadherins; Cell Adhesion Molecules; Data; Development; Disease; Embryo; Event; Family; Genes; Glaucoma; Goals; Injury; Knowledge; Lead; Left; Mammals; Mediating; Modeling; Molecular; Mus; Pathway interactions; Pattern; Process; Proteins; Research; Retinal; Retinal Ganglion Cells; Route; Specificity; Testing; Transgenic Mice; Visual; Visual Pathways; Visual system structure; abstracting; cadherin 7; cadherin-6; cohort; design; injured; knock-down; novel; postnatal; programs; research study; response; response to injury; selective expression; superior colliculus Corpora quadrigemina; visual information

Project Summary/Abstract The overall goal of this research program is to understand how parallel retinofugal pathways are established during development. This proposal focuses on the question of how retinal ganglion cell (RGC) axons select their correct targets and target layers in the brain during development. RGC axon-target and axon-layer matching are both critical aspects of visual circuit organization and yet, very little is known about how they develop in mammals. We propose to study the development of these connections in transgenic mice where specific RGC subtypes express fluorescent proteins and in which specific genes are absent or misexpressed in the retinofugal pathway. The specific aims of this proposal are to 1) characterize the cellular events that enable RGCs carrying different qualities of visual information to recognize their appropriate targets in the brain, 2) test the hypothesis that the adhesion molecule cadherin-6 controls RGC axon-target matching 3) test the hypothesis that lamina specific targeting of axons from direction selective RGCs to the superior colliculus is mediated by the adhesion molecule cadherin-7. Results from these experiments should lead to new understanding of how mammalian visual circuits are established and inform strategies for maintaining and replenishing visual circuits in response to injury or disease.

项目总结/摘要 这项研究计划的总体目标是了解如何并行视网膜离体 在发展过程中建立了通道。本建议的重点是 视网膜神经节细胞（RGC）轴突如何选择正确的目标和目标层， 大脑在发展过程中RGC轴突-靶和轴突-层匹配都是关键 视觉回路组织的各个方面，然而，关于它们是如何发展的， 在哺乳动物中。我们建议在转基因动物中研究这些连接的发展， 特定RGC亚型表达荧光蛋白且特定RGC亚型表达荧光蛋白的小鼠 脱视网膜途径中基因缺失或错误表达。具体目标是 建议是1）表征使RGC能够携带不同的 视觉信息的质量，以识别其在大脑中的适当目标，2）测试 粘附分子钙粘蛋白-6控制RGC轴突靶点的假设 匹配3）测试假设，从方向的轴突的层特异性靶向 粘附分子介导RGCs选择性地进入上级丘 钙粘蛋白-7。这些实验的结果应该会导致对 哺乳动物的视觉回路建立，并告知维持和 在受伤或疾病时补充视觉回路。