Two adhesive systems cooperatively regulate axon ensheathment and myelin growth in the CNS
Two adhesive systems cooperatively regulate axon ensheathment and myelin growth in the CNS
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DOI：
10.1038/s41467-019-12789-z
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发表时间：
2019-10-22
影响因子：
16.6
通讯作者：
Simons, Mikael
中科院分区：
文献类型：
--
作者：
Djannatian, Minou;Timmler, Sebastian;Simons, Mikael
中枢神经系统髓鞘是由少突胶质细胞产生的多层膜，以增加神经加工速度和效率，但轴突选择和髓鞘包裹的分子机制尚不清楚。在这里，在小鼠和斑马鱼的形态学和分子分析相结合，我们表明，粘附分子的paranodal和internodal段协同工作，利用重叠的功能来调节轴突的相互作用和髓鞘包装。在没有这些粘附系统的情况下，髓鞘的轴突识别受损，髓鞘生长在先前有髓鞘纤维的顶部，神经元细胞体周围和朗维尔结上方。此外，髓磷脂包裹被扰乱，前缘远离轴突移动并位于先前形成的层之间。这些数据显示了两个粘附系统如何共同作用以引导轴突鞘化和髓鞘包裹，并提供了对髓鞘空间组织如何实现的机械理解。
Central nervous system myelin is a multilayered membrane produced by oligodendrocytes to increase neural processing speed and efficiency, but the molecular mechanisms underlying axonal selection and myelin wrapping are unknown. Here, using combined morphological and molecular analyses in mice and zebrafish, we show that adhesion molecules of the paranodal and the internodal segment work synergistically using overlapping functions to regulate axonal interaction and myelin wrapping. In the absence of these adhesive systems, axonal recognition by myelin is impaired with myelin growing on top of previously myelinated fibers, around neuronal cell bodies and above nodes of Ranvier. In addition, myelin wrapping is disturbed with the leading edge moving away from the axon and in between previously formed layers. These data show how two adhesive systems function together to guide axonal ensheathment and myelin wrapping, and provide a mechanistic understanding of how the spatial organization of myelin is achieved.