CLONAL LINES OF THE NERVOUS SYSTEM

描述：(改编自申请者摘要)目前 在求学期间，应聘者形成了强大的标准化文化 研究少突胶质细胞分化和髓鞘的系统 反映体内发育事件的队形。使用这个 方法，OL祖细胞可以根据以下方面进行实验性调节 增殖分化，导致常规生产 扩展、发育同步、特定于世系阶段的 大量的细胞。申请者正在使用这个系统来分析 OL前体进入终端分化时发生的关键事件 并开始合成髓鞘膜。他们现在将调整他们的 OL末端分子机制分析的研究进展 分化与髓鞘的生物发生。下一步的具体目标是 因此，项目期是：1)确定关键组件和 OL囊泡转运系统的分子机制是 对髓鞘的生物发生、维持和再髓鞘形成至关重要。在……里面 特别是，他们将研究小的GTP结合蛋白，这些蛋白起到 囊泡形成和载体运输的调节因子，识别 这个家族的新成员，并定义他们的功能；2)描述 成纤维细胞生长因子调节OL的机制 增殖分化。重点将放在 确定成纤维细胞生长因子受体和辅助受体的变化谱系， 并理解这种复杂性的功能意义；3) 建立OL-神经元的共同分化。在以下情况下工作 合理假设原发OL分化与髓鞘 形成是在髓鞘再生过程中发生的事件的一个模型 病理情况，如多发性硬化症，这些研究已经 为临床干预做出贡献的强大潜力鼓励 脱髓鞘损伤的修复。

DESCRIPTION: (adapted from Applicant's Abstract) During the present period of study, the applicants have standardized a powerful culture system for studying oligodendrocyte (OL) differentiation and myelin formation that reflects developmental events in vivo. Using this approach, OL progenitors can be experimentally regulated with regard to proliferation and differentiation, resulting in the routine production of expanded, developmentally synchronized, lineage stage-specific populations of cells. The applicants are using this system to analyze key events that occur as OL progenitors enter terminal differentiation and begin to synthesize myelin membrane. They will now orient their studies towards an analysis of molecular mechanisms of OL terminal differentiation and myelin biogenesis. The specific aims of this next project period are therefore to: 1) identify key components and molecular mechanisms of the OL vesicular trafficking system that are critical for myelin biogenesis, maintenance, and remyelination. In particular, they will study the small GTP-binding proteins that act as regulators of vesicle formation and vectorial transport, identifying novel members of this family, and defining their function; 2) Delineate the mechanism by which fibroblast growth factor (FGF) regulates OL proliferation and differentiation. Emphasis will be placed on identifying the changing repertoire of FGF receptors and co-receptors, and understanding the functional significance of this complexity; 3) Establish an OL-neuronal co-differentiation. Working under the reasonable hypothesis that primary OL differentiation and myelin formation is a model for events occurring during remyelination in pathological situations such as multiple sclerosis, these studies have the strong potential to contribute to clinical intervention to encourage the repair of demyelinated lesions.