CLONAL LINES OF THE NERVOUS SYSTEM

神经系统的克隆系

• 批准号: 6139458
• 负责人: STEVEN E PFEIFFER
• 金额: $ 29.77万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-01-01 至 2001-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6139458
• 关键词: cell differentiation; cell growth regulation; clone cells; developmental neurobiology; fibroblast growth factor; growth factor receptors; guanine nucleotide binding protein; intracellular transport; myelin; myelination; neurogenesis; neurons; oligodendroglia; protein biosynthesis; vesicle /vacuole; cell differentiation; cell growth regulation; clone cells; developmental neurobiology; fibroblast growth factor; growth factor receptors; guanine nucleotide binding protein; intracellular transport; myelin; myelination; neurogenesis; neurons; oligodendroglia; protein biosynthesis; vesicle /vacuole

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.

描述：（改编自申请人的摘要） 学习期，申请人已经标准化了强大的文化 研究少突胶质细胞（OL）分化和髓磷脂的系统 反映体内发展事件的形成。 使用此 方法，可以在实验中对祖细胞进行实验调节 增殖和分化，导致常规产生 扩展，发育同步的谱系特定于阶段 细胞种群。 申请人正在使用此系统进行分析 当OL祖细胞进入终端分化时发生的关键事件 并开始合成髓鞘膜。 他们现在将定向他们的 研究OL末端分子机制的研究 分化和髓磷脂生物发生。 接下来的具体目标 因此，项目期限为：1）确定关键组件和 Ol囊泡贩运系统的分子机制 对于髓磷脂生物发生，维持和透明度至关重要。 在 特别是，他们将研究起作用的小型GTP结合蛋白 囊泡形成和矢量运输的调节器，识别 这个家庭的新成员，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 确定FGF受体和共受体的曲目不断变化的曲目， 并了解这种复杂性的功能意义； 3） 建立ol-神经元共差异化。 在 合理的假设是主要分化和髓磷脂 形成是在remer髓期间发生的事件的模型 病理状况，例如多发性硬化症，这些研究具有 有助于临床干预措施的强大潜力 脱髓鞘病变的修复。