OLIGODENDROCYTE ONTOGENY AND DIFFERENTIATION

髓磷脂是神经元中包围轴突的多层膜鞘。 中枢神经系统和PNS，有助于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， 组装和维持髓鞘作为一个复杂的解剖和 功能结构每个少突胶质细胞延伸出几个树突 每个突起终止于髓鞘。髓磷脂成分是 通过易位在少突胶质细胞内区域性分布，和 在髓磷脂形成的部位组装。髓鞘的合成 需要分选机制，通过该机制， 被少突胶质细胞机制识别并递送到 髓鞘组装的位点。这一过程可能受到神经元的调节。 少突胶质细胞树突与轴突相互作用后的信号。我们 建议使用细胞培养，基因突变，生化， 免疫化学、生物物理学和分子生物学技术， 调节髓鞘碱性蛋白组装的机制， 髓鞘的结构成分，进入少突胶质细胞髓鞘膜 在与神经元的原代培养物中的少突胶质细胞分化期间。 我们的长期目标是描绘髓鞘的各个步骤， 形态发生，以确定其调节模式，并确定 它们背后的分子机制。更好地理解 髓鞘形成的过程，并最终维持髓鞘， 修复，可能导致治疗，免疫化学，药物或 遗传的，用于患有CNS脱髓鞘疾病的患者 和PNS如多发性硬化和格林-巴利综合征，以及 治疗性照射后脱髓鞘疾病患者 和病毒感染。

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 dendritic processes each terminating in a myelin sheath. Myelin components are regionally distributed within the oligodendrocyte by translocation, and assembled at the site of myelin formation. The synthesis of myelin thus requires sorting mechanisms by which specific myelin components are recognized by the oligodendrocyte cellular machinery and delivered to the site of myelin assembly. This process may be regulated by neuronal signals upon interaction of an oligodendrocyte dendrite with an axon. We propose to use cell culture, genetic mutations, biochemical, immunochemical, biophysical and molecular biology techniques to study the mechanisms regulating the assembly of myelin basic protein, a major structural component of myelin, into the oligodendrocyte myelin membrane during oligodendrocyte differentiation in primary culture with neurons. Our long term objectives are to delineate the various steps in myelin morphogenesis, to determine their pattern of regulation and identify the molecular mechanisms underlying them. 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 viral infections.