Involvement of the myelin-associated inhibitor Nogo-A in early cortical development and neuronal maturation
Involvement of the myelin-associated inhibitor Nogo-A in early cortical development and neuronal maturation
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DOI：
10.1093/cercor/bhl146
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发表时间：
2007-10-01
期刊：
影响因子：
3.7
通讯作者：
del Rio, Jose A.
中科院分区：
文献类型：
--
作者：
Meur, Ana Mingorance-Le;Zheng, Binhai;del Rio, Jose A.
Nogo-A是由中枢神经系统中的神经元和髓鞘形成成熟少突胶质细胞表达的髓鞘相关蛋白。虽然大多数研究都集中在Nogo-A参与成年轴突再生和可塑性的预防，很少有人注意到Nogo-A在胚胎发育过程中的假定功能。在这里，我们研究了Nogo-A在产前小鼠端脑的一般模式和细胞特异性分布。此外，我们研究了Nogo-A/ B/C基因敲除小鼠主要轴突束的发育以及径向和切向迁移。Nogo-A在放射状神经胶质细胞和有丝分裂后神经元中的分布模式不同，其中Nogo-A在发育中的轴突中特别丰富。同样，Nogo-A在切向迁移的中间神经元的前导过程中富集，但在径向迁移的神经元中检测不到。虽然低水平的Nogo-A似乎在许多皮层神经元的表面上，但大多数蛋白质具有细胞内定位。在Nogo缺陷的背景下，神经元显示早期极化和增加的分支在体外，可能反映了Nogo蛋白在分支减少的细胞内在作用，和早期切线迁移延迟。在这些观察的基础上，我们提出，Nogo蛋白，特别是Nogo-A，参与在皮层发育过程中的多个过程。
Nogo-A is a myelin-associated protein expressed by neurons and myelinating mature oligodendrocytes in the central nervous system. Although most research has focused on the participation of Nogo-A in the prevention of axonal regeneration and plasticity in the adult, little attention has been paid to the putative functions of Nogo-A during embryonic development. Here we examined the general pattern and cell-specific distribution of Nogo-A in the prenatal mouse telencephalon. In addition, we studied the development of the major axon tracts and radial and tangential migration in Nogo-A/ B/C knockout mice. The pattern of Nogo-A showed distinct distribution in radial glia and postmitotic neurons, in which it is particularly enriched in developing axons. Similarly, Nogo-A was enriched at the leading process of tangentially migrating interneurons but not detectable in radial migrating neurons. Although a low level of Nogo-A appears to be on the surface of many cortical neurons, most proteins have intracellular localization. In Nogo-deficient background, neurons displayed early polarization and increased branching in vitro, probably reflecting a cell-intrinsic role of Nogo proteins in branching reduction, and early tangential migration was delayed. On the basis of these observations, we propose that Nogo proteins, particularly Nogo-A, are involved in multiple processes during cortical development.