Neocortical astrogenesis follows neuronogenesis and precedes oligogenesis. Among key factors dictating its temporal articulation, there are progression rates of pallial stem cells (SCs) towards astroglial lineages as well as activation rates of astrocyte differentiation programs in response to extrinsic gliogenic cues. In this study, we showed that high Foxg1 SC expression antagonizes astrocyte generation, while stimulating SC self-renewal and committing SCs to neuronogenesis. We found that mechanisms underlying this activity are mainly cell autonomous and highly pleiotropic. They include a concerted downregulation of 4 key effectors channeling neural SCs to astroglial fates, as well as defective activation of core molecular machineries implementing astroglial differentiation programs. Next, we found that SC Foxg1 levels specifically decline during the neuronogenic-to-gliogenic transition, pointing to a pivotal Foxg1 role in temporal modulation of astrogenesis. Finally, we showed that Foxg1 inhibits astrogenesis from human neocortical precursors, suggesting that this is an evolutionarily ancient trait.

中文翻译：

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Foxg1拮抗新皮质干细胞向星形胶质细胞的发展。

新皮层的星形胶质细胞生成发生在神经元发生之后，并在寡聚发生之前。在指示其时间表达的关键因素中，有部分干细胞向星形胶质细胞谱系进展的速度，以及星形胶质细胞分化程序对外源性胶质生成线索的反应的激活率。在这项研究中，我们表明高Foxg1 SC表达拮抗星形胶质细胞的生成，同时刺激SC自我更新，并使SC参与神经元发生。我们发现这一活动的基础机制主要是细胞自主性和高度多效性。它们包括协调一致地下调将神经SC引导到星形胶质细胞命运的4个关键效应子，以及激活实施星形胶质细胞分化程序的核心分子机器的缺陷激活。下一个，我们发现，SC Foxg1的水平在神经原性向胶质转换的过程中特别下降，表明在星形胶质发生的时间调控中具有关键作用的Foxg1起作用。最后，我们表明Foxg1抑制了人类新皮质前体的星形胶质细胞生成，表明这是一个进化上的古老特征。