MOLECULES REGULATING VISUAL NEURON NUMBER & AXON GROWTH

描述：（来自申请人的摘要）本项目的长期目标 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 在哺乳动物中枢神经系统的发育过程中， 产生和随后的部分消除神经元和选择性 稳定/消除未成熟的轴突节段。 研究者 提出了对视网膜神经节细胞（RGC）的影响的检查 两种互补操作的存活和连通性：1）慢性 在发育中将过量的神经营养素递送至选定的视网膜靶点 将通过植入细胞系遗传地获得仓鼠 被改造成过度表达神经营养因子 仓鼠视网膜投影 系统是一个完善的模型，用于研究生产过剩， 随后部分消除未成熟的神经元及其连接， 发育中的神经元之间潜在的竞争性相互作用及其 轴突 2)视网膜发育中的慢性神经营养素缺乏 小鼠的投射系统将通过一个或多个基因的无效突变产生。 神经营养因子基因 这些实验的两个重要方面被注意到： 他们强调了神经营养素在决定神经元功能中的作用， 未成熟轴突干和分支的存活;并且，他们调查了 多种神经营养因子的联合作用和 发育中的神经元对不同神经营养因子的相对依赖性。 这些实验将研究神经营养因子竞争的作用 在控制程序性视网膜神经节细胞死亡的发育过程中 在未成熟视网膜神经节细胞的选择性稳定/消除中 轴突节 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术后。 格局的变化 神经连接和神经营养因子的表达发生在视觉系统中， 由于各种原因， 早期的周边视觉缺陷。 因此，了解 神经营养因子在程序性细胞死亡和神经元发育中的作用 连通性可能会建议改善相关缺陷的策略， 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.