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Molecular mechanisms of bidirectional axon- oligodendrocytes signaling during the initial stages of myelination

髓鞘形成初始阶段双向轴突-少突胶质细胞信号传导的分子机制

基本信息

批准号：
13680889
负责人：
ITOH Kouichi
金额：
$ 2.3万
依托单位：
Tokyo Metropolitan Medical Research Organization
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13680889/
关键词：
Myelin Oligodendrocyte Axon Neural cell adhesion molecule L1 Cell culture

项目摘要

The goal of the study was to investigate the molecular mechanisms of bidirectional axon- oligodendrocytes (OL) signaling during the initial stages of myelination by testing the hypothesis : Mediators of initial axon-to-OL signaling include the neural cell adhesion molecule L1 on OL as well as axonal L1.1. New culture techniques to purify oligodendrocyte precursor cells (OPC) and OL.To search for genes/molecules that control the differentiation of OL, I developed a new cell culture system to get a large number of purified OPC and OL. OPC (NG2+, O1-) cultures were prepared from an embryonic 15〜16 days-old rat cerebrum.2. The expression pattern of L 1 during the development of OL.These studies provide the first evidence that expression of L1 appears in OL, but is absent in OPC. The results suggest that this differential expression pattern of L1 may have functional significance in the initial mechanisms of myelination in brain.3. Relationship between OL and myelination in vitro.The mechanisms controlling myelination at the cellular level are not fully understood. To understand these molecular processes between axon and OL, I developed in vitro myelination system. OL was co-cultured with primary neurons in the presence of astrocytes. These results indicated that L1 is expressed on premeylinated axons and OL, but is down-regulated on fully myelinated axons and OL.The results suggest that this differential expression pattern of L I may have functional significance in the initial mechanisms of myelination in brain.

本研究的目的是通过验证以下假设来研究髓鞘形成初始阶段双向轴突-少突胶质细胞（OL）信号传导的分子机制：初始轴突-OL信号传导的介质包括OL上的神经细胞粘附分子L1以及轴突L1.1。分离纯化少突胶质前体细胞（OPC）和寡突胶质前体细胞（OL）的新培养技术。为了寻找控制OL分化的基因/分子，我开发了一种新的细胞培养系统，以获得大量纯化的OPC和OL。从15 ~ 16日龄的胚胎大鼠大脑制备OPC（NG 2+，O 1-）培养物.这些研究首次证明了L1在OL中表达，而在OPC中不表达。结果提示L1的这种差异表达模式可能在脑髓鞘形成的初始机制中具有功能意义. OL与体外髓鞘形成之间的关系：在细胞水平上控制髓鞘形成的机制尚未完全了解。为了了解轴突和OL之间的这些分子过程，我开发了体外髓鞘形成系统。OL与原代神经元在星形胶质细胞的存在下共培养。这些结果表明，L1在有髓前轴突和OL上表达，而在完全有髓轴突和OL上表达下调。结果表明，L1的这种差异表达模式可能在脑髓鞘形成的初始机制中具有功能意义。