SCHWANN CELL-AXON INTERACTIONS DURING DEVELOPMENT

发育中的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， 在轴突的鞘化和髓鞘形成中达到高潮。 雪旺 已经提出细胞在引导 轴突到目标在周围神经再生过程中， 为轴突的发育提供指导线索 然而， 关于早期轴突施旺细胞相互作用的研究 未解决 这些问题包括： 成鞘细胞和运动和感觉神经元的外周 神经，这些细胞第一次相遇的时间和地点，以及 参与其识别和粘附的分子。 我们计划 通过识别和表征分子来解决这些问题 介导雪旺细胞和轴突之间的初始粘附， 通过开发特异于雪旺氏细胞前体的标记物， 用它们来描述这些细胞在 迁移到外周，并通过确定雪旺细胞和 它们包裹的神经元来自于共同的前体。 在 更长范围的研究，我们将评估雪旺细胞在 周围神经的粘连阻滞发育 干扰轴突-许旺细胞相互作用的抗体。 这些 研究将使用蛋白质的生物化学和免疫学方法 纯化，免疫组化分析， 电子显微镜水平和逆转录病毒载体谱系标记。 虽然建议的研究重点是正常的基本问题， 周围神经的发育，研究结果可能提供有用的 深入了解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.