Establishment of myelinating schwann cells and barrier integrity between central and peripheral nervous systems depend on Sox10

Establishment of myelinating schwann cells and barrier integrity between central and peripheral nervous systems depend on Sox10
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DOI:
10.1002/glia.22310
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发表时间:
2012-05-01
期刊:
影响因子:
6.2
通讯作者:
Wegner, Michael
Wegner, Michael
中科院分区:
医学1区
文献类型:
--
作者:
Froeb, Franziska;Bremer, Magdalena;Wegner, Michael

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转录因子Sox10在雪旺细胞发育过程中表达,并已被证明对未成熟雪旺细胞的鉴定和进一步发育至关重要。在这里,我们发现在雪旺细胞中,Sox10也是建立髓鞘状态所必需的。这是由以下事实得出的结论:当Sox10被一种表达受Krox20调控元件控制的Cre重组酶删除时,小鼠会发生周围神经病变。这种神经病的特征是沿周围神经标记基因表达改变,电导率降低,和严重的持续性髓鞘退化。由于Cre重组酶在边界帽细胞中也有活性,我们还分析了胚胎发生过程中Sox10在中枢和周围神经系统边界的建立和维持中的作用。Sox10缺失不影响边界帽细胞的建立或存活,但似乎损害了屏障功能,因为表达少突胶质细胞和星形胶质细胞标记的细胞不再局限于中枢神经系统,而是在周围神经中发现。我们推断,除了在雪旺细胞中的许多作用外,Sox10对中枢和周围神经系统之间边界的完整性也很重要。(C) 2012 Wiley期刊公司
The transcription factor Sox10 is expressed throughout Schwann cell development and has already been shown to be essential for specification and for the identity and further development of immature Schwann cells. Here, we show that Sox10 is also required in Schwann cells for establishing the myelinating state. This is concluded from the fact that a peripheral neuropathy develops in mice in which Sox10 is deleted by a Cre recombinase whose expression is under control of Krox20 regulatory elements. This neuropathy is characterized by altered marker gene expression along the peripheral nerve, decreased conductivity, and severe persistent hypomyelination. As the Cre recombinase is additionally active in boundary cap cells, we also analyzed the role of Sox10 during embryogenesis in establishment and maintenance of the boundary between central and peripheral nervous systems. Sox10 deletion did not affect establishment or survival of boundary cap cells but appeared to compromise barrier function as cells expressing oligodendrocyte and astrocyte markers were no longer restricted to the central nervous system, and instead found in peripheral nerves. We infer that in addition to its many roles in Schwann cells, Sox10 is also important for the integrity of the boundary between central and peripheral nervous systems. (C) 2012 Wiley Periodicals, Inc.