CLONAL LINES OF THE NERVOUS SYSTEM

描述：（改编自申请人的摘要）目前 学习期间，申请者已经规范了强大的文化 用于研究少突胶质细胞 (OL) 分化和髓磷脂的系统 反映体内发育事件的形成。 使用这个 方法，可以通过实验调节 OL 祖细胞 增殖和分化，导致常规生产 扩展的、发育同步的、谱系阶段特定的 细胞群。 申请人正在使用该系统来分析 OL 祖细胞进入终末分化时发生的关键事件 并开始合成髓磷脂膜。 他们现在将调整自己的方向 OL末端分子机制分析研究 分化和髓磷脂生物发生。 下一步的具体目标 因此，项目期间要： 1) 确定关键组成部分和 OL 囊泡运输系统的分子机制 对于髓鞘质的生物发生、维持和髓鞘再生至关重要。 在 特别是，他们将研究小的 GTP 结合蛋白，这些蛋白充当 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) 描绘 成纤维细胞生长因子 (FGF) 调节 OL 的机制 增殖和分化。 重点将放在 识别 FGF 受体和辅助受体不断变化的全部功能， 并理解这种复杂性的功能意义； 3） 建立 OL-神经元共分化。 工作在 合理的假设是原发性 OL 分化和髓磷脂 形成是髓鞘再生过程中发生事件的模型 病理情况，如多发性硬化症，这些研究已经 促进临床干预的巨大潜力，以鼓励 脱髓鞘病变的修复。

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.