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（OPCs）在netrin-1缺陷小鼠脊髓中的发育。OPCs通过olig1和PDGF受体α的原位杂交检测。Olig1阳性OPCs首先在E12.5脊髓腹侧室区（VZ）观察到。与野生型或杂合子（野生/杂合子）小鼠相比，netrin-1敲除小鼠的olig1阳性结构域位于更侧侧。随着OPC起始位点的腹侧移位，VZ区nkx2.2表达域在腹侧减少，pax6阳性域在腹侧扩大。因此，I类和II类基因的表达都受到netrin-1缺乏的影响，背腹轴的腹侧部分向腹侧移位。然而，在野生/异源和基因敲除小鼠中，地板板的形成及其音hedgehog基因的表达似乎是相似的。在OPCs出现之前，在pMN结构域中观察到少突胶质细胞和运动神经元的共同前体，其中细胞被标记为Olig2。pMN结构域在E10.5脊髓中的位置在野生/异源小鼠和敲除小鼠中似乎是相同的，而在E11.5敲除小鼠中，pMN结构域在E12.5中向腹侧移动。目前的观察表明，netrin-1可能参与确定OPC起源位置的精确位置，也可能参与背腹侧轴的形成，特别是其腹侧结构域。

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.