Brg1-Dependent Chromatin Remodelling Is Not Essentially Required during Oligodendroglial Differentiation
Brg1-Dependent Chromatin Remodelling Is Not Essentially Required during Oligodendroglial Differentiation
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DOI：
10.1523/jneurosci.1468-14.2015
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发表时间：
2015-01-07
影响因子：
5.3
通讯作者：
Wegner, Michael
中科院分区：
文献类型：
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作者：
Bischof, Melanie;Weider, Matthias;Wegner, Michael
脊椎动物周围神经系统中的髓鞘形成雪旺细胞依赖于Brg1（Smarca 4）进行终末分化。Brg1作为染色质重塑BAF复合物的中央ATP水解亚基，并在髓鞘形成过程中被雪旺细胞中的转录因子Sox 10招募为这些复合物的一部分。在这里，我们分析了Brg1在小鼠中枢神经系统中髓鞘形成少突胶质细胞发育过程中的作用。在少突胶质细胞前体中Brg1缺失后，这些细胞表现出正常的存活、增殖和迁移。一个温和的，但显着的减少少突胶质细胞与髓鞘基因表达的情况下，Brg1点的贡献少突胶质细胞分化，但也表明，Brg1的作用是不太突出，比在雪旺细胞分化。此外，我们未能获得Brg1和Sox10之间的遗传相互作用与雪旺细胞中的遗传相互作用相当的证据。这表明两种类型的髓鞘形成神经胶质的调控网络和机制之间存在相似性，但确切的作用模式和功能相互作用的相关性不同，这表明髓鞘形成控制的可变性程度令人惊讶。
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.