CNS/PNS Boundary Transgression by Central Glia in the Absence of Schwann Cells or Krox20/Egr2 Function
CNS/PNS Boundary Transgression by Central Glia in the Absence of Schwann Cells or Krox20/Egr2 Function
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DOI：
10.1523/jneurosci.0017-10.2010
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发表时间：
2010-04-28
影响因子：
5.3
通讯作者：
Topilko, Piotr
中科院分区：
文献类型：
--
作者：
Coulpier, Fanny;Decker, Laurence;Topilko, Piotr
CNS/PNS界面构成细胞边界，因为它们划分了具有不同神经元和胶质内容物的区域。尽管它们对再生医学有潜在的兴趣，但哺乳动物中限制少突胶质细胞和星形胶质细胞进入中枢神经系统和限制雪旺细胞进入PNS的机制尚不清楚。为了研究外周胶质细胞和髓磷脂在CNS/PNS边界维持中的作用，我们首先使用了不同的小鼠突变体。我们发现，雪旺细胞和边界帽细胞的缺失或雪旺细胞中髓鞘形成的主要调控基因Krox20/Egr2的失活，会导致星形胶质细胞和少突胶质细胞越过CNS/PNS边界，并导致神经根轴突的髓鞘形成。相比之下，Trembler(J)突变不会发生这种迁移，它可以在不影响Krox20表达的情况下阻止PNS髓鞘形成。总之，这些数据表明CNS/PNS边界的维持需要与髓鞘形成控制分离的Krox20功能。最后，我们分析了一名患有先天性髓鞘性神经病变的人类患者，该病变与雪旺细胞中KROX20蛋白的缺失有关。本例中，神经根也受到少突胶质细胞和星形胶质细胞的侵袭。这表明中枢神经胶质越过CNS/PNS边界可能发生在人类的病理情况下，并表明其潜在机制与小鼠相同。
CNS/PNS interfaces constitute cell boundaries, because they delimit territories with different neuronal and glial contents. Despite their potential interest in regenerative medicine, the mechanisms restricting oligodendrocytes and astrocytes to the CNS and Schwann cells to the PNS in mammals are not known. To investigate the involvement of peripheral glia and myelin in the maintenance of the CNS/PNS boundary, we have first made use of different mouse mutants. We show that depletion of Schwann cells and boundary cap cells or inactivation of Krox20/Egr2, a master regulatory gene for myelination in Schwann cells, results in transgression of the CNS/PNS boundary by astrocytes and oligodendrocytes and in myelination of nerve root axons by oligodendrocytes. In contrast, such migration does not occur with the Trembler(J) mutation, which prevents PNS myelination without affecting Krox20 expression. Altogether, these data suggest that maintenance of the CNS/PNS boundary requires a Krox20 function separable from myelination control. Finally, we have analyzed a human patient affected by a congenital amyelinating neuropathy, associated with the absence of the KROX20 protein in Schwann cells. In this case, the nerve roots were also invaded by oligodendrocytes and astrocytes. This indicates that transgression of the CNS/PNS boundary by central glia can occur in pathological situations in humans and suggests that the underlying mechanisms are common with the mouse.