SURFACE AND TARGET INFLUENCED OPTIC AXON OUTGROWTH

表面和目标影响视轴突的生长

• 批准号: 3412795
• 负责人: MARK H HANKIN
• 金额: $ 7.98万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-12-01 至 1991-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3412795
• 关键词: axon; brain stem; central nervous system; developmental neurobiology; electron microscopy; graft versus host disease; laboratory mouse; laboratory rat; microscopy; mutant; nervous system transplantation; optic tract; retina; visual pathways; xenotransplantation

The aim of the proposed work is to explore the nature of cues used by optic axons to find appropriate targets in the mammalian brain. The relationship between the location of a neuron and its ability for target-directed axonal outgrowth will be explored by analyzing the projections from embryonic retinae grafted into the brainstems of newborn animals. Previously, a xenogeneic transplantation paradigm was developed in which mouse retinae are grafted into rat brains and their projections subsequently traced using mouse- specific monoclonal antibodies (directed against neuronal cell- surfaces). The proposed experiments will use these technologies to study two classes of cues: (i) those restricted to the outer surfaces of the brain, and (ii) those independent of the brain surfaces, which arise from the target region. The proposal consists of four interrelated in vivo experiments. The first will examine the patterns of axonal outgrowth from the time the projection, are first detectable. The second will examine, using light and electron microscopy, the cellular substrates utilized by retinal efferents. The third will determine the distance over which the target region influences directed axonal outgrowth. The fourth will use "eyeless" mutant mice to investigate the ability of a virgin target to support optic axon outgrowth and innervation. There are several broad objectives of these studies. First, this work will establish in vivo correlates for those axonal guidance substrates defined in vitro. In addition, these neural grafting studies address the issues of how the specificity of connections is established during development and later maintained in the mammalian CNS. Second, they provide a neuroanatomical complement to work in progress which has shown that grafted neural tissue can integrate with and function in a neural pathway. Finally, it is important that these aspects of CNS development be addressed in vivo since they are likely to be essential in understanding congenital neural defects and in designing strategies to restore functional neural circuits.

建议的工作的目的是探索使用的线索的性质 通过视神经轴突在哺乳动物大脑中找到合适的目标。 神经元的位置与其能力之间的关系 靶向轴突生长将通过分析 移植到脑干的胚胎视网膜的突起 新生动物的。 此前，异种移植 一个范例是将小鼠视网膜移植到大鼠视网膜上， 大脑和他们的投射随后用老鼠追踪， 特异性单克隆抗体（针对神经元细胞， 表面）。 拟议的实验将使用这些技术来研究两个 线索的类别：（一）那些限制在外表面的 大脑，和（ii）那些独立的大脑表面， 从目标区域产生。 该提案包括四个 相关的体内实验。 第一部分将研究 从投射开始的轴突生长模式， 第一次检测。 第二个将检查，使用光， 电子显微镜下，视网膜利用的细胞基质 传出神经 第三个将确定距离， 靶区域影响定向轴突生长。 第四 将使用“无眼”突变小鼠来研究一种 原始目标以支持视神经轴突生长和神经支配。 这些研究有几个广泛的目标。 首先 这项工作将建立在体内相关的轴突指导， 体外定义的底物。 此外，这些神经移植 研究解决了连接的特异性如何的问题 是在开发过程中建立的，后来在 哺乳动物中枢神经系统 其次，它们提供了一种神经解剖学上的补充， 这项研究表明移植的神经组织 与神经通路整合并在其中发挥作用。 最后是 重要的是，这些方面的中枢神经系统的发展， 因为它们很可能是理解 先天性神经缺陷和设计策略， 功能性神经回路