Transcription factor 4 is a class I basic helix-loop-helix transcription factor regulating gene expression. Altered TCF4 gene expression has been linked to non-syndromic intellectual disability, schizophrenia, and a severe neurodevelopmental disorder known as Pitt-Hopkins syndrome. An understanding of the cell types expressing TCF4 protein in the mouse brain is needed to help identify potential pathophysiological mechanisms and targets for therapeutic delivery in TCF4-linked disorders. Here we developed a novel green fluorescent protein reporter mouse to visualize TCF4-expressing cells throughout the brain. Using this TCF4 reporter mouse, we observed prominent expression of TCF4 in the pallial region and cerebellum of the postnatal brain. At the cellular level, both glutamatergic and GABAergic neurons express TCF4 in the cortex and hippocampus, while only a subset of GABAergic interneurons express TCF4 in the striatum. Among glial cell groups, TCF4 is present in astrocytes and immature and mature oligodendrocytes. In the cerebellum, cells in the granule and molecular layer express TCF4. Our findings greatly extend our knowledge of the spatiotemporal and cell type-specific expression patterns of TCF4 in the brain, and hence, lay the groundwork to better understand TCF4-linked neurological disorders. Any effort to restore TCF4 functions through small molecule or genetic therapies should target these brain regions and cell groups to best recapitulate TCF4 expression patterns.

中文翻译：

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出生后小鼠大脑中 TCF4 的区域和细胞类型分布。


转录因子4是调节基因表达的I类碱性螺旋-环-螺旋转录因子。 TCF4 基因表达的改变与非综合征性智力障碍、精神分裂症和称为皮特-霍普金斯综合征的严重神经发育障碍有关。需要了解小鼠大脑中表达 TCF4 蛋白的细胞类型，以帮助识别 TCF4 相关疾病的潜在病理生理机制和治疗靶点。在这里，我们开发了一种新型绿色荧光蛋白报告小鼠，用于可视化整个大脑中表达 TCF4 的细胞。使用这种 TCF4 报告小鼠，我们观察到 TCF4 在出生后大脑的大脑皮层区域和小脑中显着表达。在细胞水平上，谷氨酸能和 GABA 能神经元在皮层和海马中表达 TCF4，而只有一部分 GABA 能中间神经元在纹状体中表达 TCF4。在神经胶质细胞群中，TCF4 存在于星形胶质细胞以及未成熟和成熟的少突胶质细胞中。在小脑中，颗粒层和分子层的细胞表达 TCF4。我们的研究结果极大地扩展了我们对大脑中TCF4的时空和细胞类型特异性表达模式的认识，从而为更好地理解TCF4相关的神经系统疾病奠定了基础。任何通过小分子或基因疗法恢复 TCF4 功能的努力都应该针对这些大脑区域和细胞群，以最好地重现 TCF4 表达模式。