SURFACE AND TARGET INFLUENCED OPTIC AXON OUTGROWTH

拟议工作的目的是探索所使用的线索的性质 通过视轴突在哺乳动物的大脑中找到合适的靶点。 神经元的位置与其能力之间的关系 对于靶向轴突生长，将通过分析 胚胎视网膜移植到脑内的投射 新生的动物。此前，异种移植 发展了将小鼠视网膜移植到大鼠体内的范例 大脑和它们的投射随后用老鼠追踪- 特异性单抗(针对神经细胞- 曲面)。 拟议的实验将使用这些技术来研究两个 球杆类别：(I)仅限于球杆表面的球杆 大脑，以及(Ii)与大脑表面无关的那些，它们 从目标区域产生。该提案由四个部分组成 相互关联的活体实验。第一个将检查 自投射时起轴突生长的模式如下 第一个可以检测到的。第二个将检查，使用光和 电子显微镜，视网膜利用的细胞底物 传出物。第三个将确定在多长时间内 靶区影响定向轴突生长。第四次 将使用“盲目”突变小鼠来研究 维珍的目标是支持视轴突的生长和神经支配。 这些研究有几个广泛的目标。首先，这是 这项工作将在体内建立这些轴突引导的相关性 在体外定义的底物。此外，这些神经移植 研究解决的问题是连接的专一性如何 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，它们提供了神经解剖学上的补充 已经表明移植的神经组织可以 与神经通路整合在一起并在其中发挥作用。最后，它是 重要的是，CNS开发的这些方面在 活体，因为它们可能是理解 先天性神经缺陷及其修复策略的设计 功能神经回路。

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.