Netrin-1 is required for the normal development of spinal cord oligodendrocytes
Netrin-1 is required for the normal development of spinal cord oligodendrocytes
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DOI：
10.1523/jneurosci.3571-05.2006
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发表时间：
2006-02-15
影响因子：
5.3
通讯作者：
Miller, RH
中科院分区：
文献类型：
--
作者：
Tsai, HH;Macklin, WB;Miller, RH
成功的中枢神经系统髓鞘形成取决于少突胶质细胞的正确定位及其与相邻轴突的相互作用。在脊髓中，少突胶质细胞前体起源于腹侧中线，随后迁移到白质并在那里成熟。体外研究表明这种分散是由引导分子 netrin-1 介导的。在这里，我们发现，在 netrin-1 突变小鼠的脊髓中，由于缺乏极化和定向迁移，少突胶质细胞前体未能从腹侧中线分散。 netrin-1 的缺乏还导致少突胶质细胞系细胞的总体减少，这与初始分散的失败无关。注射到假定白质中的少突胶质细胞前体在野生型宿主中经历了广泛的径向迁移和扩张，但在 netrin-1 突变宿主中却没有。这些数据表明，netrin-1 对于脊髓少突胶质细胞前体的初始分散及其随后在假定白质中的发育至关重要。
Successful CNS myelination is dependent on the correct localization of oligodendrocytes and their interactions with adjacent axons. In the spinal cord, oligodendrocyte precursors originate at the ventral midline and subsequently migrate to the white matter where they mature. In vitro studies suggest this dispersal is mediated by the guidance molecule netrin-1. Here, we show that in the spinal cord of netrin- 1 mutant mice, oligodendrocyte precursors failed to disperse from the ventral midline as a consequence of a lack of polarization and directional migration. The lack of netrin- 1 also resulted in an overall reduction of oligodendrocyte lineage cells that was independent of the failure of initial dispersal. Oligodendrocyte precursors injected into presumptive white matter underwent extensive radial migration and expansion in wild-type but not netrin-1 mutant hosts. These data indicate that netrin- 1 is crucial for both the initial dispersal of spinal cord oligodendrocyte precursors and their subsequent development in the presumptive white matter.