FORMATION OF NEURAL PATHWAYS IN THE AMPHIBIAN EMBRYO

对这项提案中提出的问题的回答将为以下人提供见解 在最困难和最耐人寻味的发展过程中， 日本血吸虫胚胎中枢神经系统神经连接的形成 脊椎动物。讨论了两个具体问题：(1)神经纤维是如何 被引导到发育中的中枢神经系统中的适当目标？ (2)有哪些因素会影响人与人之间的功能联系 这些过程和它们的目标细胞？大多数实验都是 描述了对不同基因类型的两栖动物进行胚胎手术，或 不同的胚胎阶段将被用来明确测试拟议的角色 对于(1)可扩散因素，(2)神经冲动活动，(3)时机。 这些实验的结果将通过询问(1)进一步寻求 神经通路形成过程中使用的线索是否常见 对于不同的脊椎动物物种，(2)如果消除任何单一线索 不干扰轴突导航是否消除 线索的组合做到了这一点，以及(3)我们能否证明轴突 导航到体外的目标。一种带延时视频的文化系统 记录也将用于分析对视网膜轴突的转向反应 靶组织渗出的或从靶组织提取的因子。的长期目标是 这项研究将确定特定的生物因素和它们的 在神经发育中的作用。这样的知识将使我们能够专注于 对这些因素的逐一关注，最终达到了细胞和 对神经连接形成的分子理解。是这样的 关于以下方面的知识也可能具有重要的医学价值 人胎脑畸形的防治。

Answers to the questions posed in this proposal would offer insights to one of the most difficult and intriguing of developmental processes, the formation of neural connections in the embryonic central nervous system of vertebrates. Two specific issues are addressed: (1) How are nerve fibers guided to their proper targets in the developing central nervous system? (2) What factors influence the formation of functional connections between these processes and their target cells? The majority of the experiments described use embryonic surgery on amphibians, different genotypes, or different embryonic stages will be used to explicitly test proposed roles for (1) diffusable factors, (2) neural impulse activity, (3) timing. Results from these experiments will be further pursued by asking (1) whether cues that are used in the formation of neural pathways are common to different vertebrate species, (2) if the elimination of any single cue does not interfere with axonal navigation whether the elimination of combinations of cues does so, and (3) whether we can demonstrate axonal navigation to a target in vitro. A culture system with time-lapse video recording will also be used to assay turning responses to retinal axons to factors exuded by or extracted from target tissues. The long term goal of this research would be to identify specific biological factors and their roles in neural development. Such knowledge would allow us to focus attention on these factors individually and finally come to a cellular and molecular understanding of the formation of neural connections. Such knowledge might also be of significant medical value with respect to the prevention and treatment of malformation in human fetal brain.