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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Sox10 regulates ciliary neurotrophic factor gene expression in Schwann cells
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Sox10 regulates ciliary neurotrophic factor gene expression in Schwann cells

机译：Sox10调节雪旺细胞中睫状神经营养因子基因的表达

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摘要

Ciliary neurotrophic factor (Cntf) plays an essential role in postnatal maintenance of spinal motoneurons. Whereas the expression of this neurotrophic factor is low during embryonic development, it is highly up-regulated after birth in myelinating Schwann cells of rodents. To characterize the underlying transcriptional mechanisms, we have analyzed and compared the effects of various glial transcription factors. In contrast to Pit-1, Oct-1, Unc-86 homology region (POU) domain class 3, transcription factor 1 (Oct6/SCIP/Tst-1) and paired box gene 3 (Pax3), SRY-box-containing gene 10 (Sox10) induces Cntf expression in Schwann cells. Subsequent promoter analysis using luciferase reporter gene and EMSA identified the corresponding response elements within the Cntf promoter. Overexpression of Sox10 in primary sciatic nerve Schwann cells leads to a > 100-fold up-regulation of Cntf protein, and suppression of Sox10 by RNA interference in the spontaneously immortalized Schwann cell line 32 reduces Cntf expression by > 80%. Mice with heterozygous inactivation of the Sox10 gene show significantly reduced Cntf protein levels in sciatic nerves, indicating that Sox10 is necessary and sufficient for regulating Cntf expression in the peripheral nervous system.
机译：睫状神经营养因子（Cntf）在脊髓运动神经元的产后维持中起着至关重要的作用。尽管该神经营养因子的表达在胚胎发育过程中较低，但在出生后在啮齿类动物的有髓雪旺细胞中被高度上调。为了表征潜在的转录机制，我们分析并比较了各种神经胶质转录因子的作用。与Pit-1，Oct-1，Unc-86同源区域（POU）域3类，转录因子1（Oct6 / SCIP / Tst-1）和配对盒基因3（Pax3），含SRY盒的基因相反10（Sox10）在雪旺氏细胞中诱导Cntf表达。随后使用荧光素酶报道基因和EMSA进行启动子分析，确定了Cntf启动子中的相应应答元件。 Sox10在原代坐骨神经雪旺细胞中的过度表达导致Cntf蛋白的上调> 100倍，而RNA干扰在自发永生的Schwann细胞系32中抑制Sox10会使Cntf表达降低> 80％。 Sox10基因杂合失活的小鼠显示坐骨神经中Cntf蛋白水平显着降低，这表明Sox10对调节周围神经系统中Cntf的表达是必要和充分的。

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