Progression of Neurogenesis in the Inner Ear Requires Inhibition of Sox2 Transcription by Neurogenin1 and Neurod1
Progression of Neurogenesis in the Inner Ear Requires Inhibition of Sox2 Transcription by Neurogenin1 and Neurod1
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DOI：
10.1523/jneurosci.4030-12.2013
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发表时间：
2013-02-27
影响因子：
5.3
通讯作者：
Wu, Doris K.
中科院分区：
文献类型：
--
作者：
Evsen, Lale;Sugahara, Satoko;Wu, Doris K.
Sox2是中枢神经系统中神经元形成所必需的，但其分子机制尚不清楚。在这里，我们讨论了Sox2在发育中的鸡内耳神经发生中的作用。从组成型（β -肌动蛋白）启动子过表达Sox2诱导原基因Neurogenin1 （Ngn1）的表达；然而，Ngn1的下游靶点Neurod1的表达不变。因此，在发育中的耳蜗前庭神经节中，分层和填充的神经前体减少。相反，Ngn1或Neurod1的过表达足以促进该系统的神经命运。这些结果表明，高水平的Sox2抑制发育中的内耳神经发生的进展。此外，我们提供的证据表明，Ngn1和Neurod1通过系统发育保守的Sox2增强子抑制Sox2转录，介导神经发生。我们认为Sox2通过促进Ngn1的表达而赋予神经能力，而Ngn1对Sox2的负反馈抑制是神经前体向新生神经元发展的重要步骤。
Sox2 is required for proper neuronal formation in the CNS, but the molecular mechanisms involved are not well characterized. Here, we addressed the role of Sox2 in neurogenesis of the developing chicken inner ear. Overexpressing Sox2 from a constitutive (beta-actin) promoter induces the expression of the proneural gene, Neurogenin1 (Ngn1); however, the expression of a downstream target of Ngn1, Neurod1, is unchanged. As a result, there is a reduction of neural precursors to delaminate and populate the developing cochleovestibular ganglion. In contrast, overexpression of either Ngn1 or Neurod1 is sufficient to promote the neural fate in this system. These results suggest that high levels of Sox2 inhibit progression of neurogenesis in the developing inner ear. Furthermore, we provide evidence that Ngn1 and Neurod1 inhibit Sox2 transcription through a phylogenetically conserved Sox2 enhancer to mediate neurogenesis. We propose that Sox2 confers neural competency by promoting Ngn1 expression, and that negative feedback inhibition of Sox2 by Ngn1 is an essential step in the progression from neural precursor to nascent neuron.