Waisman Center, University of Wisconsin, Madison, WI, USA.
Nucleic Acids Res. 2012 Aug;40(14):6449-60. doi: 10.1093/nar/gks313. Epub 2012 Apr 9.
Myelin is essential for the rapidity of saltatory nerve conduction, and also provides trophic support for axons to prevent axonal degeneration. Two critical determinants of myelination are SOX10 and EGR2/KROX20. SOX10 is required for specification of Schwann cells from neural crest, and is required at every stage of Schwann cell development. Egr2/Krox20 expression is activated by axonal signals in myelinating Schwann cells, and is required for cell cycle arrest and myelin formation. To elucidate the integrated function of these two transcription factors during peripheral nerve myelination, we performed in vivo ChIP-Seq analysis of myelinating peripheral nerve. Integration of these binding data with loss-of-function array data identified a range of genes regulated by these factors. In addition, although SOX10 itself regulates Egr2/Krox20 expression, leading to coordinate activation of several major myelin genes by the two factors, there is a large subset of genes that are activated independent of EGR2. Finally, the results identify a set of SOX10-dependent genes that are expressed in early Schwann cell development, but become subsequently repressed by EGR2/KROX20.
髓鞘对于跳跃式神经传导的速度至关重要，它还为轴突提供营养支持，以防止轴突退化。髓鞘形成的两个关键决定因素是 SOX10 和 EGR2/KROX20。SOX10 是神经嵴来源的施万细胞特化所必需的，并且在施万细胞发育的每个阶段都需要。Egr2/Krox20 的表达受髓鞘形成施万细胞中的轴突信号激活，并且对于细胞周期停滞和髓鞘形成是必需的。为了阐明这两个转录因子在外周神经髓鞘形成过程中的综合功能，我们对有髓神经进行了体内 ChIP-Seq 分析。将这些结合数据与功能丧失阵列数据进行整合，确定了一系列受这些因子调控的基因。此外，尽管 SOX10 本身可以调节 Egr2/Krox20 的表达，导致这两个因子共同激活几个主要的髓鞘基因，但也有很大一部分基因的激活是不依赖于 EGR2 的。最后，结果确定了一组 SOX10 依赖性基因，它们在施万细胞早期发育中表达，但随后被 EGR2/KROX20 抑制。
