Notch signaling promotes astrogliogenesis via direct CSL-mediated glial gene activation
Notch signaling promotes astrogliogenesis via direct CSL-mediated glial gene activation
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DOI：
10.1002/jnr.10364
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发表时间：
2002-09-15
影响因子：
4.2
通讯作者：
Sun, YE
中科院分区：
文献类型：
--
作者：
Ge, WH;Martinowich, K;Sun, YE
在发育中的中枢神经系统（CNS）中，Notch信号传导保留祖细胞库并抑制神经发生和少突胶质细胞分化。最近有人推测Notch可诱导星形胶质细胞分化。Notch信号在促进星形胶质细胞分化中的作用是允许的还是指导性的一直存在争议。我们在这里报告的星形胶质细胞的作用，Notch的部分介导的直接结合的Notch细胞内结构域的CSL DNA结合蛋白，形成一个转录激活复合物的星形胶质细胞标记基因，胶质细胞酸性蛋白（GFAP）。此外，我们发现，在CSL-/-神经干细胞培养物中，星形胶质细胞分化延迟，但一旦启动就以正常速率继续，这表明CSL参与调节星形胶质细胞生成的发生。重要的是，尽管经典的CSL依赖性Notch信号传导途径是完整的，并且能够在神经发生阶段激活Notch经典靶启动子，但它不能在神经发生期间激活GFAP启动子。因此，Notch信号对靶基因的作用受到神经发生和胶质细胞生成调节中的细胞环境的影响。(C)2002 Wiley-Liss，Inc.
In the developing central nervous system (CNS), Notch signaling preserves progenitor pools and inhibits neurogenesis and oligodendroglial differentiation. It has recently been postulated that Notch instructively drives astrocyte differentiation. Whether the role of Notch signaling in promoting astroglial differentiation is permissive or instructive has been debated. We report here that the astrogliogenic role of Notch is in part mediated by direct binding of the Notch intracellular domain to the CSL DNA binding protein, forming a transcriptional activation complex onto the astrocyte marker gene, glial fibrillary acidic protein (GFAP). In addition, we found that, in CSL-/- neural stem cell cultures, astrocyte differentiation was delayed but continued at a normal rate once initiated, suggesting that CSL is involved in regulating the onset of astrogliogenesis. Importantly, although the classical CSL-dependent Notch signaling pathway is intact and able to activate the Notch canonical target promoter during the neurogenic phase, it is unable to activate the GFAP promoter during neurogenesis. Therefore, the effect of Notch signaling on target genes is influenced by cellular context in regulation of neurogenesis and gliogenesis. (C) 2002 Wiley-Liss, Inc.