SCHWANN CELL-AXON INTERACTIONS DURING DEVELOPMENT

发育过程中的施万细胞轴突相互作用

基本信息

批准号：
2266337
负责人：
ROBERT W BRACKENBURY
金额：
$ 17.09万
依托单位：
UNIVERSITY OF CINCINNATI
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-04-01 至 1995-03-31
项目状态：
已结题

项目摘要

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.

发展神经元与 Schwann细胞会导致外周神经躯干形成最终导致轴突和髓磷脂形成。 Schwann 已经提议细胞在指导中发挥重要作用周围神经再生期间靶向靶标的轴突，可能为开发轴突提供指导线索。但是，几乎没有关于早期轴突schwann细胞相互作用的已知。未解决问题包括分院细胞以及周围的电动机和感觉神经元神经，这些细胞第一次相遇的时间和地点，以及分子参与其识别和粘附。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，通过开发特定于Schwann细胞前体的标记和用它们描述这些细胞在这些细胞之后的路径通过确定schwann细胞和是否迁移到外围它们所包含的神经元来自常见的前体。在长期研究我们将评估雪旺细胞在通过使用粘附阻滞的周围神经的发展抗体轴突 - 切恩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，免疫组织化学分析在光线和电子显微镜水平和逆转录病毒载体谱系标记。拟议的研究重点是正常的基本问题周围神经的发展，发现可能会提供有用了解我们对脱髓鞘疾病和神经再生。