Sun Lijuan, Xiong Feng, Huang Feier, Dong Shuangshuang, Zhu Pei, Jiang Pengfei, Zhang Baoshen, Zhang Xinxin, Sun Jie, Peng Hanchuan, Zhao Chunjie
Key Laboratory of Developmental Genes and Human Diseases, Ministry of Education, School of Medicine, Southeast University, Nanjing, China.
New Cornerstone Science Laboratory, Institute for Brain and Intelligence, Southeast University, Nanjing, China.
Nat Commun. 2025 May 30;16(1):5032. doi: 10.1038/s41467-025-60338-8.
The activity of the telencephalon is shaped by pallial and subpallial GABAergic neurons, two large populations produced in the embryonic ganglionic eminence. However, knowledge about the fate specification of neuron subtypes is limited, especially whether there is a common mechanism directing the fate choice of pallial versus subpallial populations remains unknown, largely because each population comprises numerous subtypes. Here, using sc-RNA sequencing combined with loss-of-function we profile ganglion eminence lineages and find that Foxg1 deletion causes the pallial population to adopt subpallial fates in mice. We delineate developmental trajectories and reveal FOXG1-driven transcriptional programs that specify neuron subtypes in each GE lineage and transcription factors that direct lineage bifurcation decisions. We uncover a common mechanism that drives pallial fate over subpallial fate across ganglion eminence lineages. Our study illuminates the control of production between pallial and subpallial populations and offers transcriptomic insights into the pathogenesis of GABAergic neuron-related disorders.
端脑的活动由皮质和皮质下的γ-氨基丁酸能神经元塑造，这两类大量的神经元产生于胚胎神经节隆起。然而，关于神经元亚型命运特化的知识有限，尤其是是否存在指导皮质与皮质下神经元群体命运选择的共同机制仍不清楚，这主要是因为每个群体都包含众多亚型。在这里，我们结合单细胞RNA测序与功能缺失方法对神经节隆起谱系进行分析，发现Foxg1基因敲除会使小鼠的皮质神经元群体呈现皮质下命运。我们描绘了发育轨迹，揭示了由FOXG1驱动的转录程序，这些程序决定了每个神经节隆起谱系中的神经元亚型，以及指导谱系分支决定的转录因子。我们发现了一种跨神经节隆起谱系驱动皮质命运而非皮质下命运的共同机制。我们的研究阐明了皮质和皮质下神经元群体产生的调控机制，并为γ-氨基丁酸能神经元相关疾病的发病机制提供了转录组学见解。
