FORMATION OF NEURAL PATHWAYS IN THE EMBRYO

该提案旨在测试关于指导意见的具体内容 胚胎脊椎动物大脑中正在生长的视网膜轴突。这 假设表明稳定的位置线索排列在 神经上皮细胞膜和生长中的轴突可以阅读 这些位置提示并使用它们导航到它们的目标 区域。启发提出这一观点的发现 假说是视网膜轴突可以从 大脑中各种不同的起点表明 分布式制导机制，以及其他几种可能的 轴突引导机制在这个系统中已经很清楚了。 排除了。有一种可能性从来没有确定过 在体内测试，是视网膜定向生长的想法 纤维是由于趋化性使生长锥体向上扩散 顶盖吸引剂的梯度。我们的前三个实验是 旨在将这种可能性与假设区分开来 结合在膜上的位置线索。 我们提出了一系列的两个实验，旨在提供 轴突的时空形态信息 神经上皮细胞中的引导信号。这将开始 对指导线索的表征，因此将内置于 关于从第一组中获得的结果的重要途径 实验。 视网膜轴突在体外可以表现出对膜的明显偏好 来自不同的大脑区域。我们的下一组实验 将在描述地形的这些偏好中做出选择 系统在体外。我们将询问发现的地形是否与 是从轴突引导的位置线索假说中预测的。 最后，我们将考虑位置提示的可能性 在放射状神经胶质细胞的末端脚上产生的可能是印记 在大脑的基底膜上。我们设计了一种活体内 将视网膜外植体定向移植到 基底膜。 我们即将了解神经元的基本原理 在脊椎动物的大脑中寻路。所描述的实验 这里可以巩固这种理解，并将问题带到 一种新的细胞和分子水平的分析。

The proposal is designed to test a specific regarding the guidance of growing retinal axons in the embryonic vertebrate brain. This hypotheses states the stable positional cues are arrayed on the membranes of neuroepithelial cells and that growing axons can read these positional cues and use them to navigate to their target area. The findings which inspired the formulation of this hypothesis are that retinal axons can grow toward the tectum from a variety of different starting points in the brain suggesting a distributed guidance mechanism, and that several other plausible mechanisms of axonal guidance in this system have been clearly ruled out. One possibility which has never been definitively tested in vivo, is the idea that the directed growth of retinal fibers is due to chemotaxis of the growth cone up a diffusible gradient of a tectal attractant. Our first three experiments are geared toward distinguishing this possibility from the hypothesis of membrane-bound positional cues. We propose a series of two experiments designed to provide information of the temporal and spatial appearance of axonal guidance cues in the neuroepithelium. This will begin the characterization of the guidance cues, and will thus build in an important way on the results obtained from the first set of experiments. Retinal axons can show distinct preferences in vitro for membranes derived from different brain areas. Our next set of experiments will be to describe the topography of these preferences in a choice system in vitro. We will ask if the topography found matches what is predicted from the position cues hypothesis of axonal guidance. Finally, we will consider the possibility that positional cues generated on the endfeet of radial glial cells may be imprinted onto the basement membrane of the brain. We devise an in vivo experiment in which retinal explant are plated directed onto basement membrane. We are on the verge of understanding basic principles of neuronal pathfinding in the vertebrate brain. The experiments described here could consolidate this understanding and bring the problem to a new cellular and molecular level of analysis.