MOLECULES REGULATING VISUAL NEURON NUMBER & AXON GROWTH

描述：(摘自申请人S摘要)这项工作的长远目标 该项目旨在阐明调节细胞和分子机制 视觉系统发育过程中的神经连接模式。在 在哺乳动物的中枢神经系统发育过程中，有大量的 神经元的产生和随后的部分消除以及选择性 稳定/消除未成熟轴突节段。调查员 提出了一项对视网膜神经节细胞(RGC)影响的研究 两种互补手法的存活率和连通性：1)慢性 在发育过程中将过量的神经营养因子输送到选定的视网膜靶点 仓鼠将通过基因植入细胞系来实现 被设计成过度表达神经营养因子。仓鼠视网膜投射 系统是一个成熟的模型，用于研究过剩和 随后部分消除未成熟神经元及其连接和 发育中神经元之间的潜在竞争相互作用及其 轴突。2)发育中视网膜的慢性神经营养素剥夺 小鼠的投影系统将由一个或多个零突变产生 神经营养因子基因。这些实验的两个重要方面值得注意： 他们强调了神经营养因子在决定神经营养因子中的作用。 未成熟轴突主干和分支的存活；他们研究了 多种神经营养因子的联合作用与脑缺血时相变化 发育中的神经元对不同神经营养因子的相对依赖性。 这些实验将检验竞争神经营养因子的作用。 在控制视网膜神经节细胞程序性死亡的发展过程中 在未成熟视网膜神经节细胞选择性稳定/消除中的作用 轴突节段。细胞程序性死亡与神经营养因子表达的变化 发生在几种人类疾病和轴突切断后。模式中的变化 神经连接和神经营养因子的表达发生在视觉中 系统由于各种原因导致视觉体验异常 生命早期的外周视力缺陷。因此，理解 神经营养因子与细胞程序性死亡和神经元发育 连通性可能会提出一些策略来改善相关的缺陷 患有这些疾病和各种发育障碍。

DESCRIPTION: (from the applicant s abstract) The long term goal of this project is to elucidate the cellular and molecular mechanisms that regulate pattern of neural connections during visual system development. In the developing mammalian central nervous system, there is a massive over production and subsequent partial elimination of neurons and the selective stabilization/elimination of immature axon segments. The investigator proposes an examination of the effects on retinal ganglion cell (RGC) survival and connectivity of two complimentary manipulations: 1) Chronic delivery of excess neurotrophins to selected retinal targets in developing hamsters will be achieved by implantation of cell lines genetically engineered to overexpress neurotrophins. The hamster retinal projection system is a well-established model for studying the over production and subsequent partial elimination of immature neurons and their connections and the underlying competitive interactions among developing neurons and their axons. 2) Chronic neurotrophin deprivation in the developing retinal projection system of mice will be produced by null mutations of one or more neurotrophin genes. Two important aspects of these experiments are noted: they emphasize the rarely studied role of neurotrophins in determining the survival of immature axon trunks and branches; and, they investigate the combined actions of multiple neurotrophins and temporal changes in the relative dependence of developing neurons on different neurotrophins. The experiments will examine the role of competition for neurotrophins during development in the control of programmed retinal ganglion cell death in the selective stabilization/elimination of immature retinal ganglion cell axon segments. Programmed cell death and changes in neurotrophin expression occur in several human diseases and after axotomy. Changes in the pattern of neural connections and in neurotrophin expression occur within the visual system as a consequence of abnormal visual experience due to various peripheral visual defects early in life. Thus, understanding the role of neurotrophins in programmed cell death and the development of neuronal connectivity may suggest strategies to ameliorate the deficits associated with these conditions and with various developmental disorders.