OLIGODENDROCYTE ONTOGENY AND DIFFERENTIATION

髓磷脂是围绕轴突的多层膜鞘 CNS 和 PNS，通过以下方式促进神经冲动的快速传导 跳跃式传导。 在中枢神经系统中，少突胶质细胞合成， 组装并维持髓鞘作为一个复杂的解剖学和 功能结构。 每个少突胶质细胞各自延伸出几个过程 终止于髓鞘。 为了实现生产和 大量膜的定向组装，细胞在空间上 通过重新分配其合成机器来组织其合成机器 细胞骨架元件。 这个假设将通过微观检验 细胞器和细胞骨架的分布分析 髓磷脂形成各个阶段的少突胶质细胞中的元素。 髓磷脂成分局部分布在少突胶质细胞内 和髓鞘。 因此，髓磷脂的合成需要分选 特定髓磷脂成分被识别的机制 少突胶质细胞机器并输送到髓磷脂部位 装配。 髓磷脂碱性蛋白的分选发生在 它的 mRNA，沿着突起运输到髓鞘 与少突胶质细胞骨架相关的复合物。我们建议 通过使用原位杂交来表征该复合物， 免疫细胞化学，E.N.定位和代谢抑制剂。 我们的长期目标是描述和表征各种 髓磷脂形态发生的步骤。 更好地理解过程 髓磷脂的形成，以及最终髓磷脂的维护和修复，可以 导致免疫化学、药物或遗传疗法 患有中枢神经系统和PNS脱髓鞘疾病的患者，例如 多发性硬化症和格林巴利综合征，以及患有以下疾病的患者 治疗性辐射后的脱髓鞘病症和 化疗或病毒感染。

Myelin is the multilamellar membranous sheath that surrounds axons in the CNS and the PNS, contributing to fast conduction of nerve impulses by saltatory conduction. In the CNS, the oligodendrocyte synthesizes, assembles, and maintains the myelin sheath as a complex anatomical and functional structure. Each oligodendrocyte extends several processes each terminating in a myelin sheath. In order to achieve the production and directional assembly of this large amount of membrane, the cell spatially organizes its synthetic machinery through the redistribution of its cytoskeletal elements. This hypothesis will be tested by microscopic analysis of the distribution of cellular organelles and cytoskeletal elements in oligodendrocytes at various stages of myelin formation. Myelin components are regionally distributed within the oligodendrocytes and the myelin sheath. Thus, the synthesis of myelin requires sorting mechanisms by which specific myelin components are recognized by the oligodendrocyte cellular machinery and delivered to the site of myelin assembly. The sorting of myelin basic protein takes place at the level of its mRNA, which is transported down the processes to the myelin sheath in a complex associated with the oligodendrocyte cytoskeleton. We propose to characterize this complex by the use of in situ hybridization, immunocytochemistry, E.N. localization, and metabolic inhibitors. Our long term objectives are to delineate and characterize the various steps in myelin morphogenesis. A better understanding of the process of myelin formation, and eventually of myelin maintenance and repair, could lead to therapies, immunochemical, pharmaceutical, or genetic, for patients afflicted with demyelinating diseases of the CNS and PNS, such as multiple sclerosis and Guillain-Barre syndrome, and for patients with demyelinating conditions following therapeutic irradiation and chemotherapy or viral infections.