Plag1 regulates neuronal gene expression and neuronal differentiation of neocortical neural progenitor cells
Plag1 regulates neuronal gene expression and neuronal differentiation of neocortical neural progenitor cells
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DOI：
10.1111/gtc.12718
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发表时间：
2019-10-01
期刊：
影响因子：
2.1
通讯作者：
Kishi, Yusuke
中科院分区：
文献类型：
--
作者：
Sakai, Hiroshi;Fujii, Yuki;Kishi, Yusuke
神经祖细胞（npc，也称为径向胶质祖细胞）在小鼠新皮层发育过程中产生神经元，然后产生星形胶质细胞等胶质细胞。鉴于神经细胞的连续生成对于大脑的正常形成至关重要，npc的神经发生潜能必须得到精确控制。在这里，我们发现转录因子Plag1在小鼠新皮质npc的神经发生潜能调控中起重要作用。我们发现Hmga2是新皮质NPCs中一个关键的神经源性因子，可诱导Plag1基因的表达。对Plag1过表达或敲低的影响的分析表明，在胚胎新皮层培养中，Plag1以星形胶质细胞的产生为代价促进神经元的产生。此外，在体内，Plag1的过表达促进了新皮质NPCs的神经元分化，而Plag1的敲低抑制了Plag1的分化。转录组学分析显示，Plag1增加了npc中一组神经元基因的表达。因此，我们的研究结果表明，Plag1在发育中的小鼠新皮层的npc中是神经元基因表达和神经元分化的调节因子。
Neural progenitor cells (NPCs, also known as radial glial progenitors) produce neurons and then glial cells such as astrocytes during development of the mouse neocortex. Given that this sequential generation of neural cells is critical for proper brain formation, the neurogenic potential of NPCs must be precisely controlled. Here, we show that the transcription factor Plag1 plays an important role in the regulation of neurogenic potential in mouse neocortical NPCs. We found that Hmga2, a key neurogenic factor in neocortical NPCs, induces expression of the Plag1 gene. Analysis of the effects of over-expression or knockdown of Plag1 indicated that Plag1 promotes the production of neurons at the expense of astrocyte production in embryonic neocortical cultures. Furthermore, over-expression of Plag1 promoted and knockdown of Plag1 suppressed neuronal differentiation of neocortical NPCs in vivo. Transcriptomic analysis showed that Plag1 increases the expression of a set of neuronal genes in NPCs. Our results thus identify Plag1 as a regulator of neuronal gene expression and neuronal differentiation in NPCs of the developing mouse neocortex.