Mode and mechanisms of oligodendrocyte precursor cell migration: common regulation mechanisms regulating glial and neurons precursor migration

Netrin-1是一种轴突引导分子，可以吸引或排斥伸长的轴突和迁移的神经细胞。在这里，我们展示了少突胶质前体细胞(OPC)在Netrin-1缺陷小鼠脊髓中的发育。OPC采用Olig-1和PDGF受体α原位杂交法检测。首次在E12.5脊髓的腹侧脑室带(VZ)观察到OPCs呈寡聚1阳性。与野生型或杂合子(野生型/杂合子)小鼠相比，Netrin-1基因敲除小鼠的Orig1阳性结构域位于更腹侧。随着OPC起始点的腹移，Nkx2.2表达区域在VZ腹向缩小，Pax6阳性区域在VZ腹向扩大。因此，I类和II类基因的表达都受到Netrin-1缺乏的影响，并且背腹轴的腹侧部分发生了腹移。然而，在野生/异种小鼠和基因敲除小鼠中，声波刺猬的底板的形成及其表达似乎是相似的。在OPC出现之前，在PMN区域观察到了少突胶质细胞和运动神经元的共同前体，其中的细胞被标记为Opol2。在野生型/杂交型和基因敲除小鼠中，PMN结构域在E10.5脊髓中的位置似乎是相同的，而在E11.5基因敲除小鼠中，PMN结构域的位置与E12.5中的位置一样发生了腹移。本研究结果提示，netrin-1可能参与确定OPC起源部位的确切位置，也可能参与背腹轴的形成，特别是其腹侧区。

Netrin-1 is an axon guidance molecule which attracts or repels elongating axons and migrating neural cells. Here we demonstrate development of oligodendrocyte precursor cells (OPCs) in the netrin-1 deficient mouse spinal cord. OPCs were detected by in situ hybridization of Olig-1 and PDGF receptor alpha. Olig1 -positive OPCs were first observed in the ventral ventricular zone (VZ) of the E12.5 spinal cord. Olig1-positive domain of the netrin-1 knockout mouse is positioned more ventrally than that of wild type or of heterozygote (wild/hetero) mouse. In accordance with the ventral shift of the site of OPC origin, Nkx2.2-expressing domain is reduced ventrally and Pax6-positive domain is expanded ventrally in the VZ. Thus, expression of both class I and class II genes was affected by netrin-1 deficiency, and the ventral part of the dorsoventral axis is shifted ventrally. However, formation of the floor plate and its expression of sonic hedgehog seemed to be similar between wild/hetero and knockout mice. Before the appearance of OPCs, common precursors for oligodendrocytes and motor neurons are observed in the pMN domain, in which cells are labeled with Olig2. The position of pMN domain in E10.5 spinal cord appears to be the same in both the wild/hetero and knockout mice whereas that was shifted in E11.5 knockout mouse as ventrally as in E12.5. The present observation suggests that netrin-1 may be involved in the determination of the precise position of the site of OPC origin and probably also in the dorsoventral axis formation, especially its ventral domains.