CNRS, UMR 7102, Paris, France.
Glia. 2012 Oct;60(10):1590-604. doi: 10.1002/glia.22378. Epub 2012 Jul 9.
Myelination is regulated by extracellular proteins, which control interactions between oligodendrocytes and axons. Semaphorins are repulsive axon guidance molecules, which control the migration of oligodendrocyte precursors during normal development and possibly in demyelinating diseases. We show here that the transmembrane semaphorin 6A (Sema6A) is highly expressed by myelinating oligodendrocytes in the postnatal mouse brain. In adult mice, Sema6A expression is upregulated in demyelinating lesions in cuprizone-treated mice. The analysis of the optic nerve and anterior commissure of Sema6A-deficient mice revealed a marked delay of oligodendrocyte differentiation. Accordingly, the development of the nodes of Ranvier is also transiently delayed. We also observed an arrest in the in vitro differentiation of purified oligodendrocytes lacking Sema6A, with a reduction of the expression level of Myelin Basic Protein. Their morphology is also abnormal, with less complex and ramified processes than wild-type oligodendrocytes. In myelinating co-cultures of dorsal root ganglion neurons and purified oligodendrocytes we found that myelination is perturbed in absence of Sema6A. These results suggest that Sema6A might have a role in myelination by controlling oligodendrocyte differentiation.
髓鞘形成受到细胞外蛋白的调节，这些蛋白控制着少突胶质细胞与轴突之间的相互作用。信号素是排斥性的轴突导向分子，它控制着少突胶质细胞前体细胞在正常发育过程中的迁移，并且可能在脱髓鞘疾病中发挥作用。我们在这里表明，跨膜信号素 6A（Sema6A）在出生后小鼠大脑中有髓鞘形成的少突胶质细胞中高度表达。在成年小鼠中，Sema6A 的表达在杯状醇处理的脱髓鞘病变中上调。对 Sema6A 缺陷小鼠视神经和前连合的分析表明，少突胶质细胞分化明显延迟。相应地，Ranvier 结的发育也暂时延迟。我们还观察到缺乏 Sema6A 的纯化少突胶质细胞在体外分化过程中停滞，少突胶质细胞碱性蛋白的表达水平降低。它们的形态也异常，与野生型少突胶质细胞相比，它们的突起更简单、分支更少。在背根神经节神经元和纯化少突胶质细胞的共培养中，我们发现缺乏 Sema6A 会干扰髓鞘形成。这些结果表明，Sema6A 可能通过控制少突胶质细胞分化在髓鞘形成中发挥作用。
