Abstract Inhibitory neurons of the telencephalon are generated from progenitors in the ganglionic eminences that mature and differentiate into specialized cell types. Here, we used single cell transcriptomics and single cell chromatin accessibility together with lineage tracing and birthdating techniques to investigate the influence of progenitor competence on the development of GABAergic precursors. We found that the timing of neurogenesis influences the maturation competence of progenitors to develop towards a fully functional state, but not their differentiation competence to evolve into transcriptomically diverse states. The underlying mechanism defining maturation competence was chromatin priming, orchestrated by the transcription factor Nfib in collaboration with regulators of inhibitory neuron development. Finally, transplantation experiments revealed an interplay between both intrinsic and extrinsic cues acting upon maturation competence. These findings identify a mechanism that coordinates inhibitory neuron development by changing its maturation to achieve maximum adaptability to their environment.

Nfib regulates progenitor competence in maturation of GABAergic neurons