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.

中文翻译：

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Plag1调节新皮层神经祖细胞的神经元基因表达和神经元分化。

在小鼠新皮层的发育过程中，神经祖细胞（NPC，也称为放射状神经胶质祖细胞）先产生神经元，然后产生神经胶质细胞，例如星形胶质细胞。鉴于神经细胞的这种顺序生成对于适当的大脑形成至关重要，因此必须精确控制NPC的神经源性潜力。在这里，我们表明转录因子Plag1在小鼠新皮层NPC的神经源性潜力的调节中起着重要作用。我们发现Hmga2，在新皮层NPC中的关键神经源性因子，诱导Plag1基因的表达。分析Plag1的过表达或敲低的影响表明，Plag1以胚胎新皮层培养物中星形胶质细胞的产生为代价来促进神经元的产生。此外，Plag1的过表达促进和Plag1的敲低抑制体内新皮层NPC的神经元分化。转录组分析显示，Plag1增加了NPC中一组神经元基因的表达。因此，我们的结果确定了Plag1是发育中的小鼠新皮层NPC中神经元基因表达和神经元分化的调节剂。