Development of retinofugal parallel pathways

描述（由申请人提供）：本研究计划的总体目标是了解在发育过程中如何建立平行的离视网膜途径。该建议的重点是视网膜神经节细胞（RGC）轴突如何在发育过程中选择正确的靶点和靶层的问题。RGC轴突-目标和轴突-层匹配都是视觉回路组织的关键方面，然而，很少有人知道它们在哺乳动物中是如何发展的。我们建议在转基因小鼠中研究这些连接的发展，其中特定的RGC亚型表达荧光蛋白，并且其中特定的基因在离视网膜途径中不存在或错误表达。该提议的具体目的是1）表征使携带不同质量的视觉信息的RGC能够识别其在大脑中的适当目标的细胞事件，2）检验粘附分子钙粘蛋白-6控制RGC轴突-靶标匹配的假设3）检验以下假设：从方向选择性RGCs到上级丘的轴突的层特异性靶向是由粘附介导的分子钙粘蛋白-7。这些实验的结果应该会导致对哺乳动物视觉回路是如何建立的新的理解，并为维持和补充视觉回路以应对损伤或疾病提供信息。 公共卫生相关性：我们研究的长期目标是了解中央视觉通路在发育过程中是如何建立的，以及这些连接如何在疾病或损伤时得以维持或补充。从这些研究中获得的知识将特别与影响视网膜与中央目标连接的视觉系统疾病相关，例如青光眼。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: The long-term objectives of our research are to understand how central visual pathways are established during development and how those connections can be maintained or replenished in response to diseases or injuries that degrade them. Knowledge gained from these studies will be particularly relevant to diseases of the visual system that impact retinal connections with central targets, such as glaucoma.