Hes5 regulates the transition timing of neurogenesis and gliogenesis in mammalian neocortical development
Hes5 regulates the transition timing of neurogenesis and gliogenesis in mammalian neocortical development
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DOI：
10.1242/dev.147256
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发表时间：
2017-09-01
期刊：
影响因子：
4.6
通讯作者：
Ohtsuka, Toshiyuki
中科院分区：
文献类型：
--
作者：
Bansod, Shama;Kageyama, Ryoichiro;Ohtsuka, Toshiyuki
神经干/祖细胞（neural stem/progenitor cells，NSCs）在哺乳动物新皮层发育过程中，从胚胎中晚期开始分化为深层神经元和浅层神经元，在围产期进入胶质形成期。以前，我们发现Hes基因抑制神经元分化并维持NSC。在这里，我们产生了在中枢神经系统的神经干细胞中过度表达Hes 5的转基因小鼠，并发现从深层到浅层神经发生的过渡时间提前，而胶质细胞发生早熟地发生在Hes 5过度表达小鼠的发育中的新皮层。相比之下，从深层到浅层神经发生的过渡和胶质细胞生成的开始在Hes 5基因敲除（KO）小鼠中延迟。我们发现Hmga基因（Hmga 1/2）在Hes 5过表达脑的新皮层区域下调，而在Hes 5 KO脑中上调。此外，我们发现Hes 5的表达导致Hmga 1/2启动子活性的抑制。这些结果表明，Hes 5调节的过渡时间之间的阶段，为规范的新皮层神经元和神经发生和胶质细胞之间，伴随着Hgma基因的表达水平的改变，在哺乳动物新皮层发育。
During mammalian neocortical development, neural stem/progenitor cells (NSCs) sequentially give rise to deep layer neurons and superficial layer neurons through mid-to late-embryonic stages, shifting to gliogenic phase at perinatal stages. Previously, we found that the Hes genes inhibit neuronal differentiation and maintain NSCs. Here, we generated transgenic mice that overexpress Hes5 in NSCs of the central nervous system, and found that the transition timing from deep to superficial layer neurogenesis was shifted earlier, while gliogenesis precociously occurred in the developing neocortex of Hes5-overexpressing mice. By contrast, the transition from deep to superficial layer neurogenesis and the onset of gliogenesis were delayed in Hes5 knockout (KO) mice. We found that the Hmga genes (Hmga1/2) were downregulated in the neocortical regions of Hes5-overexpressing brain, whereas they were upregulated in the Hes5 KO brain. Furthermore, we found that Hes5 expression led to suppression of Hmga1/2 promoter activity. These results suggest that Hes5 regulates the transition timing between phases for specification of neocortical neurons and between neurogenesis and gliogenesis, accompanied by alteration in the expression levels of Hgma genes, in mammalian neocortical development.