Bright Ann Rose, Kotlyarenko Yana, Neuhaus Florian, Rodrigues Diana, Feng Chao, Peters Christian, Vitali Ilaria, Dönmez Elif, Myoga Michael H, Dvoretskova Elena, Mayer Christian
Max Planck Institute for Biological Intelligence, Martinsried, Germany.
Max Planck Institute of Neurobiology, Martinsried, Germany.
Nat Neurosci. 2025 Jul 8. doi: 10.1038/s41593-025-01999-y.
Diverse types of GABAergic projection neuron and interneurons of the telencephalon derive from progenitors in a ventral germinal zone called the ganglionic eminence. Using single-cell transcriptomics, chromatin accessibility profiling, lineage tracing, birthdating, transplantation across developmental stages and perturbation sequencing in mouse embryos, we investigated how progenitor competence influences the maturation and differentiation of these neurons. We found that the temporal progression of neurogenesis shapes maturation competence in ganglionic eminence progenitors, influencing how their progeny progress toward mature states. By contrast, differentiation competence-defined as the ability of progenitors to produce diverse transcriptomic identities-was maintained throughout neurogenesis. Chromatin remodeling, together with a regulatory module composed of the transcription factor NFIB and its target genes, influenced maturation competence in late-born neurons. These findings reveal how transcriptional programs and chromatin accessibility govern neuronal maturation and the diversification of GABAergic neuron subtypes during neurodevelopment.
端脑的多种类型的γ-氨基丁酸能投射神经元和中间神经元起源于一个称为神经节隆起的腹侧生发区的祖细胞。利用单细胞转录组学、染色质可及性分析、谱系追踪、出生时间测定、跨发育阶段移植以及小鼠胚胎中的扰动测序，我们研究了祖细胞能力如何影响这些神经元的成熟和分化。我们发现神经发生的时间进程塑造了神经节隆起祖细胞的成熟能力，影响其后代向成熟状态发展的方式。相比之下，分化能力（定义为祖细胞产生多种转录组特征的能力）在整个神经发生过程中保持不变。染色质重塑以及由转录因子NFIB及其靶基因组成的调控模块影响了晚期出生神经元的成熟能力。这些发现揭示了转录程序和染色质可及性如何在神经发育过程中控制神经元成熟以及γ-氨基丁酸能神经元亚型的多样化。
