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Diverse types of GABAergic projection neurons 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, heterochronic transplantation, and perturbation sequencing in mouse embryos, we investigated how progenitor competence influences the maturation and differentiation of these neurons. We found that the progression of neurogenesis over developmental time shapes maturation competence in ganglionic eminence progenitors, how they progress into mature states. In contrast, dierentiation competence, which defines the ability to produce diverse transcriptomic identities, remains largely unaffected by the stages of neurogenesis. Chromatin remodeling alongside a NFIB-driven regulatory gene module influences maturation competence in late-born neurons. These findings provide key insights into how transcriptional programs and chromatin accessibility govern neuronal maturation and the diversification of GABAergic neuron subtypes during neurodevelopment.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
* The new version of the manuscript contains additional experiments, including CUT&RUN, in vivo overexpression, and tCROP-seq perturbation sequencing, providing functional validation and further supporting our conclusions on the role of NFIB in neuronal progenitor regulation.
* http://141.5.108.55:3838/mind_shiny/