SCHWANN CELL-AXON INTERACTIONS DURING DEVELOPMENT

发育中的神经元和神经元之间的一系列相互作用 雪旺细胞导致周围神经干的形成和 最终形成轴突包膜和髓鞘形成。施万恩 细胞被认为在指导人类发展过程中发挥重要作用 在周围神经再生过程中轴突到靶点，并可能 为发育轴突提供指导线索。然而，几乎没有什么是 已知早期轴突雪旺细胞的相互作用。未解决 问题包括两人之间的确切血统关系 鞘细胞与外周运动神经元和感觉神经元 神经，这些细胞第一次相遇的时间和地点，以及 参与其识别和粘连的分子。我们计划 通过识别和表征分子来解决这些问题 调节雪旺细胞和轴突之间的初始黏附， 通过开发针对雪旺细胞前体和 使用它们来描述这些细胞所遵循的路径 迁移到外围，并通过确定雪旺细胞和 它们被包裹的神经元来自一种共同的前体。在……里面 更长期的研究，我们将评估雪旺细胞在 粘连阻滞法对周围神经发育的影响 干扰轴突-雪旺细胞相互作用的抗体。这些 研究将使用蛋白质的生化和免疫学方法 纯化，在光线下进行免疫组织化学分析， 电子显微镜水平和逆转录病毒载体谱系标记。 虽然拟议的研究集中在正常情况下的基本问题 对于周围神经的发育，这一发现可能会提供有用的 对我们对脱髓鞘疾病和 神经再生。

A series of reciprocal interactions between developing neurons and Schwann cells leads to formation of peripheral nerve trunks and culminates in ensheathment of axons and myelin formation. Schwann cells have been proposed to play an essential role in guidance of axons to targets during regeneration of peripheral nerves and may provide guidance cues to developing axons. However, little is known about early axon Schwann cell interactions. Unresolved questions include the exact lineage relationship between the ensheathing cells and the motor and sensory neurons of peripheral nerves, the time and place of these cells' first encounter, and the molecules involved in their recognition and adhesion. We plan to address these issues by identifying and characterizing molecules that mediate the initial adhesion between Schwann cells and axons, by developing markers specific for Schwann cell precursors and using them to describe the path followed by these cells as they migrate to the periphery, and by determining if Schwann cells and the neurons they ensheath are derived from a common precursor. In longer range studies we will evaluate the role of Schwann cells in the development of peripheral nerves by using adhesion-blocking antibodies to perturb axon-Schwann cell interactions. These studies will use biochemical and immunological methods of protein purification, immunohistochemical analysis at the light and, electron microscopic levels, and retrovirus vector lineage markers. While the proposed research focuses on basic issues in the normal development of peripheral nerves, the findings may provide useful insights into our understanding of both demyelinating disease and nerve regeneration.