CELLULAR EVENTS IN MYELINATION

髓鞘，在中枢神经系统中由 少突胶质细胞与神经元的突起密切相关 并促进神经冲动的传导。 的形成 髓磷脂是神经系统发育的重要部分， 在人类神经病理学病症中髓磷脂的破坏， 多发性硬化症与功能的急剧恶化有关。 这里提出的研究旨在了解细胞 在发育过程中有助于髓鞘形成的机制， 以及在脱髓鞘疾病的修复过程中其重新形成。 的 从增殖的前体细胞形成少突胶质细胞是 是中枢神经髓鞘形成的第一步 系统;然而，前体细胞知之甚少。 这些研究 将探测前体细胞的生物化学特性， 胸苷放射自显影和免疫细胞化学染色，以确定 增殖的少突胶质前体细胞是否含有 髓鞘特异性蛋白、髓鞘碱性蛋白和髓鞘相关蛋白 糖蛋白，如果没有，在细胞停止后的什么时间 这些蛋白质出现在发育中的少突胶质细胞中。 此外，髓鞘碱性蛋白和 髓鞘相关糖蛋白将与细胞精细结构的变化相关。 结构 神经胶质细胞的产生也将在两个 老鼠的遗传疾病，颤抖和颤抖，产生过量的 少突胶质细胞的数量。 对这种生产过剩的研究可能会提供线索 刺激正常人少突胶质细胞形成的机制 发育和髓鞘再生。 拟议的分析将确定 发育期，在此期间，多余的细胞在细胞中形成。 突变体，使用定量光学和电子显微镜。 胶质细胞生成 然后通过胸苷放射自显影检查突变体， 免疫细胞化学，以发现是否过度生产的 少突胶质细胞与干细胞相关， 与正常发育所建立的不同。

Myelin sheaths, elaborated in the central nervous system by oligodendrocytes, are intimately associated with the processes of neurons and act to facilitate the conduction of nerve impulses. The formation of myelin is a prominent part of the development of the nervous system, and the disruption of myelin in human neuropathological conditions such as multiple sclerosis is associated with dramatic deterioration of function. The studies proposed here are aimed at understanding the cellular mechanisms which contribute to the formation of myelin during development, and to its reformation during repair from demyelinating disease. The formation of oligodendrocytes from proliferating precursor cells is necessarily the first step in myelin formation in the central nervous system; however, the precursor cell is poorly understood. These studies will probe the biochemical indentity of the precursor cell by a combination of thymidine autoradiography and immunocytochemical staining, to determine whether the proliferating oligodendrocyte precursor cells contain the myelin specific protiens, myelin basic protein and myelin-associated glycoprotein and, if they do not, at what time after cessation of cell division these proteins appear in the developing oligodendrocytes. Furthermore, changes in immunoreactivity for myelin basic protein and myelin-associated glycoprotein will be correlated with changes in cell fine structure. The production of neuroglial cells will also be studied in two genetic disorders of mouse, quaking and shiverer, which produce excess numbers of oligodendrocytes. Study of this overproduction may give clues to the mechanisms which stimulate oligodendrocyte formation in normal development and in remyelination. The analysis proposed will establish the period of development during which the excess cells are formed in the mutants, using quantitative light and electron microscopy. Gliogenesis in the mutants wil then be examined by thymidine autoradiography and immunocytochemistry, to discover whether the overproduction of oligodendrocytes is associated with stem cells with characteristics similar to or different from those established for normal development.