Oligodendrocytes and axon interaction

少突胶质细胞和轴突相互作用

• 批准号: 200513589
• 负责人: Professor Dr. Mikael Jakob Simons
• 金额: --
• 依托单位: Institut für Zellbiologie des Nervensystems
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/200513589?language=en
• 关键词: Oligodendrocytes; axon; interaction

The myelin sheath is one of the most abundant membrane structures in the vertebrate nervous sys-tem. It is produced by two types of specialized glial cells, oligodendrocytes in the central nervous system, and Schwann-cells in the peripheral nervous system. Cell adhesion plays a key role in the formation of myelin. Not only the specific interaction of the glial cell with the axon, but also the adhesive interactions of the individual layers of myelin membrane are essential for the generation of the multilamellar myelin sheath. Whereas many of the axonal signals that regulate myelination in the PNS are known, the factors that control myelination of axons in the CNS by oligodendrocytes have not been identified. Oligodendrocytes seem to require unique and so far unidentified molecules for axon and oligodendrocyte interaction. The goal of this project is therefore to elucidate the mechanisms governing the onset and progression of myelination in the CNS. We plan to identify novel adhesion molecules that mediate oligodendrocyte and axon interaction. We will use a proteome approach to identify candidate molecules, expression cloning to determine the interaction partners and perform functional assays in a neuron and oligodendrodyte co-culture system. In addition, we aim at identifying the mechanism underlying the adhesive interactions of the individual layers of myelin membrane.

髓鞘是脊椎动物神经系统中最丰富的膜结构之一。它由两种类型的特化胶质细胞产生，即中枢神经系统中的少突胶质细胞和外周神经系统中的许旺细胞。细胞粘附在髓鞘的形成中起着关键作用。不仅胶质细胞与轴突的特异性相互作用，而且髓鞘膜的各个层的粘附相互作用对于多层髓鞘的产生是必不可少的。尽管许多调节PNS中髓鞘形成的轴突信号是已知的，但通过少突胶质细胞控制CNS中轴突髓鞘形成的因子尚未被鉴定。少突胶质细胞似乎需要独特的，迄今尚未确定的分子轴突和少突胶质细胞的相互作用。因此，本项目的目标是阐明中枢神经系统髓鞘形成的发生和发展的机制。我们计划确定新的粘附分子介导少突胶质细胞和轴突的相互作用。我们将使用蛋白质组学方法来鉴定候选分子，表达克隆来确定相互作用伙伴，并在神经元和少突细胞共培养系统中进行功能测定。此外，我们的目标是确定的机制，潜在的粘附相互作用的各个层的髓鞘膜。