The transcription factors Sox10 and Myrf define an essential regulatory network module in differentiating oligodendrocytes.
The transcription factors Sox10 and Myrf define an essential regulatory network module in differentiating oligodendrocytes.
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DOI：
10.1371/journal.pgen.1003907
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发表时间：
2013-10
期刊：
影响因子：
4.5
通讯作者：
Wegner M
中科院分区：
文献类型：
--
作者：
Hornig J;Fröb F;Vogl MR;Hermans-Borgmeyer I;Tamm ER;Wegner M
髓鞘是快速跳跃传导所必需的，并且由外周神经系统中的许旺细胞和中枢神经系统中的少突胶质细胞产生。在这两种细胞类型中，转录因子Sox10是髓鞘特异性调控网络的重要组成部分。在这里，我们确定Myrf作为Sox10的少突胶质细胞特异性靶点，并将Sox10响应增强子映射到Myrf基因内含子1中的进化保守元件。一旦被诱导，Myrf与Sox 10合作来实施髓鞘形成程序，这从两种蛋白质之间的物理相互作用和几种髓鞘特异性基因的协同激活中可以看出。这强烈地让人想起雪旺细胞中的情况，其中Sox 10首先诱导，然后在髓鞘形成期间与Krox 20合作。我们的分析表明，在少突胶质细胞髓鞘形成的监管网络组织沿着类似的一般原则，在雪旺细胞，但差异实施。近年来，人们已经清楚地认识到，复杂的发育过程不是由单一的转录因子调控的，而是由在复杂的调控网络中相互作用的转录因子的组合调控的。在这里，我们分析了驱动少突胶质细胞终末分化的调节网络，少突胶质细胞是脊椎动物中枢神经系统的细胞，形成髓鞘，从而保证快速跳跃式传导。我们表明，转录因子Myrf是直接激活的转录因子Sox10，并映射Sox10响应增强子的Myrf基因的内含子1中的进化保守的元素。然后，我们继续表明，一旦诱导，Myrf物理相互作用和功能合作，其诱导剂Sox10激活髓鞘基因，认为这两个共同驱动少突胶质细胞的终末分化。通过这项研究，我们定义了中枢神经系统髓鞘特异性调节网络中的一个重要模块。通过比较这个模块与相应的模块在雪旺细胞的周围神经系统，其中包括Sox10和Krox20转录因子，我们进一步得出结论，髓鞘形成在两个车厢的脊椎动物神经系统的调节相似的组织，但差异实施的监管网络。
Myelin is essential for rapid saltatory conduction and is produced by Schwann cells in the peripheral nervous system and oligodendrocytes in the central nervous system. In both cell types the transcription factor Sox10 is an essential component of the myelin-specific regulatory network. Here we identify Myrf as an oligodendrocyte-specific target of Sox10 and map a Sox10 responsive enhancer to an evolutionarily conserved element in intron 1 of the Myrf gene. Once induced, Myrf cooperates with Sox10 to implement the myelination program as evident from the physical interaction between both proteins and the synergistic activation of several myelin-specific genes. This is strongly reminiscent of the situation in Schwann cells where Sox10 first induces and then cooperates with Krox20 during myelination. Our analyses indicate that the regulatory network for myelination in oligodendrocytes is organized along similar general principles as the one in Schwann cells, but is differentially implemented. In recent years it has become clear that complex developmental processes are not regulated by single transcription factors but rather by combinations of transcription factors that interact in intricate regulatory networks. Here, we analyze the regulatory network that drives terminal differentiation of oligodendrocytes, the cells of the vertebrate central nervous system that form myelin and thereby guarantee rapid saltatory conduction. We show that the transcription factor Myrf is directly activated by the transcription factor Sox10, and map a Sox10-responsive enhancer to an evolutionarily conserved element in intron 1 of the Myrf gene. We then go on to show that once induced, Myrf physically interacts and functionally cooperates with its inducer Sox10 to activate myelin genes arguing that the two jointly drive terminal differentiation of oligodendrocytes. With this study we define an essential module in the myelin-specific regulatory network in the central nervous system. By comparing this module with the corresponding module in Schwann cells of the peripheral nervous system which consists of Sox10 and the Krox20 transcription factor we furthermore conclude that myelination in the two compartments of the vertebrate nervous system is regulated by similarly organized, but differentially implemented regulatory networks.
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DOI：
10.1083/jcb.200912142
发表时间：
2010-05-17
期刊：
The Journal of cell biology
影响因子：
--
作者：
Finzsch M;Schreiner S;Kichko T;Reeh P;Tamm ER;Bösl MR;Meijer D;Wegner M
通讯作者：
Wegner M
DOI：
10.1083/jcb.85.3.890
发表时间：
1980-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
McCarthy KD;de Vellis J
通讯作者：
de Vellis J
影响因子：
--
作者：
Jones, Erin A.;Jang, Sung-Wook;Svaren, John
通讯作者：
Svaren, John
影响因子：
5.3
作者：
Kuhlbrodt, K;Herbarth, B;Wegner, M
通讯作者：
Wegner, M
影响因子：
34.7
作者：
Meijer, Dimphna H.;Kane, Michael F.;Mehta, Shwetal;Liu, Hongye;Harrington, Emily;Taylor, Christopher M.;Stiles, Charles D.;Rowitch, David H.
通讯作者：
Rowitch, David H.