Astrocyte allocation during brain development is controlled by Tcf4-mediated fate restriction.

Yandong Zhang,Dan Li,Yuqun Cai,Rui Zou,Yilan Zhang,Xin Deng,Yafei Wang,Tianxiang Tang,Yuanyuan Ma,Feizhen Wu,Yunli Xie
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Abstract

Astrocytes in the brain exhibit regional heterogeneity contributing to regional circuits involved in higher-order brain functions, yet the mechanisms controlling their distribution remain unclear. Here, we show that the precise allocation of astrocytes to specific brain regions during development is achieved through transcription factor 4 (Tcf4)-mediated fate restriction based on their embryonic origin. Loss of Tcf4 in ventral telencephalic neural progenitor cells alters the fate of oligodendrocyte precursor cells to transient intermediate astrocyte precursor cells, resulting in mislocalized astrocytes in the dorsal neocortex. These ectopic astrocytes engage with neocortical neurons and acquire features reminiscent of dorsal neocortical astrocytes. Furthermore, Tcf4 functions as a suppressor of astrocyte fate during the differentiation of oligodendrocyte precursor cells derived from the ventral telencephalon, thereby restricting the fate to the oligodendrocyte lineage in the dorsal neocortex. Together, our findings highlight a previously unappreciated role for Tcf4 in regulating astrocyte allocation, offering additional insights into the mechanisms underlying neurodevelopmental disorders linked to Tcf4 mutations.
大脑发育过程中星形胶质细胞的分配受 Tcf4 介导的命运限制控制。
大脑中的星形胶质细胞表现出区域异质性,有助于形成参与高阶大脑功能的区域回路,但控制其分布的机制仍不清楚。在这里,我们发现星形胶质细胞在发育过程中精确分配到特定脑区是通过转录因子 4(Tcf4)介导的基于胚胎起源的命运限制来实现的。腹侧端脑神经祖细胞中 Tcf4 的缺失改变了少突胶质细胞前体细胞到瞬时中间星形胶质细胞前体细胞的命运,导致星形胶质细胞在背侧新皮质中错位。这些异位星形胶质细胞与新皮质神经元接触,并获得与背侧新皮质星形胶质细胞相似的特征。此外,在源自腹侧端脑的少突胶质细胞前体细胞分化过程中,Tcf4 起着抑制星形胶质细胞命运的作用,从而限制了背侧新皮层少突胶质细胞系的命运。总之,我们的研究结果突显了 Tcf4 在调节星形胶质细胞分配方面以前未被认识到的作用,为了解与 Tcf4 基因突变相关的神经发育障碍的机制提供了新的视角。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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