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平行的视黄醇通路是如何在发育过程中建立的。这一建议关注的是视网膜神经节细胞(RGC)轴突在发育过程中如何选择其正确的靶点和靶层的问题。RGC轴突-靶点和轴突-层匹配都是视觉回路组织的关键方面，然而，人们对它们在哺乳动物中的发展知之甚少。我们建议在转基因小鼠中研究这些连接的发展，在转基因小鼠中，特定的RGC亚型表达荧光蛋白，并且特定的基因在视黄醇途径中缺失或错误表达。这一建议的具体目的是：1)表征细胞事件，使携带不同质量视觉信息的视网膜节细胞能够识别其大脑中适当的靶点；2)检验黏附分子钙粘素-6控制视网膜节细胞轴突-靶点匹配的假设；3)检验板层特异性靶向从方向选择性视网膜节细胞到上丘的轴突是由黏附分子钙粘素-7介导的假说。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的策略提供依据。 与公共健康相关：我们研究的长期目标是了解在发育过程中中央视觉通路是如何建立的，以及如何在应对使其退化的疾病或伤害时保持或补充这些联系。从这些研究中获得的知识将特别与影响视网膜与中央靶点连接的视觉系统疾病相关，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.