OLIGODENDROCYTE ONTOGENY AND DIFFERENTIATION

描述（来自申请人的摘要）： 中枢神经系统中的少突胶质细胞的作用是产生髓鞘， 是跳跃式传导所必需的。我们的长期目标是 阐明髓鞘形成的过程及其调控。髓鞘碱性 蛋白质（MBP），鞘的主要结构成分，是必不可少的 髓鞘的形成。MBP在髓鞘中的组装位点合成 膜的这是通过将MBP mRNA从细胞核转运到细胞核来实现的。 细胞体和向下的细胞过程，并进入髓鞘，然后 锚定和平移。我们研究工作的短期目标是 这条贩运途径。这将通过以下方式实现： 表征不均一核核糖核蛋白的表达 （hnRNP）A2，识别信号的基本反式作用因子 存在于MBP mRNA中的转运序列;鉴定MBP mRNA的其他成分。 MBP mRNA运输系统，并确定其作用;表征 MBP mRNA运输被阻断或增强的条件，和 描绘了MBP mRNA从细胞核转位到髓鞘的步骤 膜和调节模式。在培养物中显微注射活细胞， 共聚焦显微镜，免疫细胞化学，Western blot，酵母双杂交 系统、免疫共沉淀和亚细胞分级分离程序将 采用 髓鞘形成不足和脱髓鞘具有严重的神经系统后果。 了解mRNA运输的机制是研究的第一步。 了解髓磷脂是如何在人的一生中被修复的， 单独的.这些知识应该导致治疗，免疫化学或 用于患有CNS脱髓鞘疾病的患者的药物 和PNS如多发性硬化症、腓骨肌萎缩症和 格林-巴利综合征，以及脱髓鞘疾病患者 治疗性放疗和化疗或病毒感染后。

DESCRIPTION (From the Applicant's Abstract): The major function of the oligodendrocyte in the CNS is to produce myelin, the membrane sheath that envelops axons and is necessary for saltatory conduction. Our long term goal is to elucidate the process of myelination and its regulation. Myelin basic protein (MBP), a major structural component of the sheath, is essential for the formation of myelin. MBP is synthesized at its site of assembly in the myelin membrane. This is accomplished by transport of MBP mRNA from the nucleus to the cell body and down the cell processes and into the myelin sheath, followed by anchoring and translation. The short term goal of our research efforts is to elucidate this trafficking pathway. This will be accomplished by: Characterizing the expression of heterogeneous nuclear ribonucleoprotein (hnRNP) A2, the essential trans-acting factor that recognizes the signal sequence for transport present in MBP mRNA; identifying other constituents of the MBP mRNA trafficking system and determining their role; characterizing the conditions under which MBP mRNA trafficking is blocked or enhanced, and delineating the steps in MBP mRNA translocation from the nucleus to the myelin membrane and pattern of regulation. Microinjection of live cell in culture, confocal microscopy, immunocytochemistry, Western blot, yeast two-hybrid system, co-immunoprecipitation and subcellular fractionation procedures will be used. Hypomyelination and demyelination have severe neurological consequences. Understanding the mechanism of mRNA trafficking is the first step in understanding how myelin is made a repaired throughout the life of an individual. This knowledge should lead to therapies, immunochemical or pharmaceutical for patients afflicted with demyelinating diseases of the CNS and PNS such as multiple sclerosis, Charcot-Marie-Tooth disease and Guillain-Barre syndrome, and for patients with demyelinating conditions following therapeutic irradiation and chemotherapy or viral infections.