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在少突胶质细胞分化过程中,并非必需Brg1依赖性染色质重塑。

Brg1-dependent chromatin remodelling is not essentially required during oligodendroglial differentiation.

作者信息

Bischof Melanie, Weider Matthias, Küspert Melanie, Nave Klaus-Armin, Wegner Michael

机构信息

Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander Universität Erlangen-Nürnberg, D-91054 Erlangen, Germany, and.

Department of Neurogenetics, Max Planck Institute of Experimental Medicine, D-37075 Goettingen, Germany.

出版信息

J Neurosci. 2015 Jan 7;35(1):21-35. doi: 10.1523/JNEUROSCI.1468-14.2015.

Abstract

Myelinating Schwann cells in the vertebrate peripheral nervous system rely on Brg1 (Smarca4) for terminal differentiation. Brg1 serves as central ATP-hydrolyzing subunit of the chromatin remodelling BAF complexes and is recruited during myelination as part of these complexes by the transcription factor Sox10 in Schwann cells. Here, we analyzed the role of Brg1 during development of myelinating oligodendrocytes in the CNS of the mouse. Following Brg1 deletion in oligodendrocyte precursors, these cells showed normal survival, proliferation, and migration. A mild but significant reduction in the number of oligodendrocytes with myelin gene expression in the absence of Brg1 points to a contribution to oligodendroglial differentiation but also shows that the role of Brg1 is much less prominent than during Schwann cell differentiation. Additionally, we failed to obtain evidence for a genetic interaction between Brg1 and Sox10 comparable with the one in Schwann cells. This argues that similarities exist between the regulatory networks and mechanisms in both types of myelinating glia but that the exact mode of action and the relevance of functional interactions differ, pointing to a surprising degree of variability in the control of myelination.

摘要

脊椎动物外周神经系统中形成髓鞘的施万细胞的终末分化依赖于Brg1(Smarca4)。Brg1作为染色质重塑BAF复合物的核心ATP水解亚基,在髓鞘形成过程中,作为这些复合物的一部分,被施万细胞中的转录因子Sox10招募。在此,我们分析了Brg1在小鼠中枢神经系统中形成髓鞘的少突胶质细胞发育过程中的作用。在少突胶质细胞前体中删除Brg1后,这些细胞表现出正常的存活、增殖和迁移。在缺乏Brg1的情况下,有髓鞘基因表达的少突胶质细胞数量出现轻微但显著的减少,这表明Brg1对少突胶质细胞分化有一定作用,但也表明Brg1的作用远不如在施万细胞分化过程中那么突出。此外,我们未能获得证据证明Brg1和Sox10之间存在与施万细胞中类似的遗传相互作用。这表明在这两种形成髓鞘的神经胶质细胞的调控网络和机制之间存在相似性,但具体的作用方式和功能相互作用的相关性有所不同,这表明在髓鞘形成的控制方面存在惊人程度的变异性。

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