Sema4D as an inhibitory regulator in oligodendrocyte development
Sema4D as an inhibitory regulator in oligodendrocyte development
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DOI：
10.1016/j.mcn.2011.12.004
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发表时间：
2012-03-01
影响因子：
3.5
通讯作者：
Inagaki, Shinobu
中科院分区：
文献类型：
--
作者：
Yamaguchi, Wataru;Tamai, Rie;Inagaki, Shinobu
对OL分化的内在调节因子的具体功能知之甚少。Sema4D最初被发现是轴突导向的负性调节因子，主要由出生后大脑中的少突胶质细胞表达，我们先前的研究发现，Sema4D的缺乏导致了大脑皮层中少突胶质细胞数量的增加，提示Sema4D可能是少突胶质细胞发育的内在调节因子。在这项研究中，我们评估了Sema4D缺乏和外源添加Sema4D对少突胶质细胞分化的影响。在出生后第14天及以后，Sema4D缺乏引起大脑皮层少突胶质细胞的数量增加，但不增加少突胶质前体细胞的数量。在从Sema4D缺陷小鼠获得的培养的少突胶质细胞中也观察到这种增加。然后，我们研究了Sema4D缺乏是否会增加祖细胞的增殖或影响其凋亡。在发育中的大脑皮层和从Sema4D基因缺陷小鼠获得的培养的少突胶质细胞中，凋亡的少突胶质细胞数量显著减少，而少突胶质前体细胞的增殖没有明显变化。外源性Sema4D的加入阻止了少突胶质细胞的这种凋亡减少，并进一步促进了少突胶质细胞的凋亡。因此，Sema4D可能通过促进细胞凋亡而发挥抑制少突胶质细胞分化的内在抑制作用。(C)2011 Elsevier Inc.保留所有权利。
The specific functions of intrinsic regulators of OL differentiation are poorly understood. Sema4D, originally found as a negative regulator of axon guidance, is mainly expressed by oligodendrocytes in the postnatal brain, and our previous study revealed that the lack of Sema4D induced an increase in the number of oligodendrocytes in the cerebral cortex, suggesting that Sema4D may function as an intrinsic regulator of oligodendrocyte development. In this study, we assessed the effects of Sema4D deficiency and of the exogenous addition of Sema4D on oligodendrocyte differentiation. Sema4D deficiency induced an increase in the number of oligodendrocytes in the cerebral cortex at postnatal day 14 and later, without increase in the number of oligodendrocyte progenitor cells. This increase was also observed in cultured oligodendrocytes obtained from Sema4D-deficient mice. Then we investigated whether Sema4D deficiency can increase the proliferation of the progenitor cells or influence the apoptosis. Apoptotic oligodendrocytes were markedly reduced in number in the developing cerebral cortex and in cultured oligodendrocytes obtained from Sema4D-deficient mice, although no significant change was found in proliferation of oligodendrocyte progenitor cells. Exogenous addition of Sema4D prevented the oligodendrocytes from this reduction of apoptosis, and further enhanced apoptosis in oligodendrocytes. Thus, Sema4D may act as an intrinsic inhibitory regulator of oligodendrocyte differentiation by promoting apoptosis. (C) 2011 Elsevier Inc. All rights reserved.