SCHWANN CELL-AXON INTERACTIONS DURING DEVELOPMENT

发育过程中的施万细胞轴突相互作用

• 批准号: 3413460
• 负责人: ROBERT W BRACKENBURY
• 金额: $ 16.43万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 1994-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3413460
• 关键词: Schwann cells; afferent nerve; axon; biomarker; cell adhesion; cell cell interaction; cell differentiation; cell migration; chickens; electron microscopy; immunocytochemistry; immunologic assay /test; laboratory rabbit; laboratory rat; microscopy; monoclonal antibody; motor neurons; myelination; neurochemistry; neurogenesis; peripheral nervous system; tissue /cell culture

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 最终形成轴突的鞘和髓磷脂的形成。 施万 细胞被提议在指导中发挥重要作用 周围神经再生过程中轴突与目标的结合可能 为轴突的发育提供指导线索。 然而，很少的是 了解早期轴突雪旺细胞相互作用。 未解决 问题包括确切的血统关系 外周的鞘细胞以及运动和感觉神经元 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， 通过开发雪旺细胞前体特异性标记物和 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 它们所包裹的神经元源自共同的前体。 在 更长期的研究我们将评估雪旺细胞在 使用粘连阻断法促进周围神经的发育 扰乱轴突-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、光免疫组织化学分析， 电子显微镜水平和逆转录病毒载体谱系标记。 虽然拟议的研究侧重于正常情况下的基本问题 周围神经的发育，这些发现可能提供有用的 深入了解我们对脱髓鞘疾病和 神经再生。