Temporal control of progenitor competence shapes maturation in GABAergic neuron development in mice

Inhibitory neurons of the telencephalon are generated from progenitors in the ganglionic eminences that mature and differentiate into specialized cell types. Here, we used scRNA-seq and scATAC-seq together with lineage tracing and birthdating techniques to investigate the influence of neurogenesis timing on the development of GABAergic precursors. We found that the timing of neurogenesis substantially influences the progenitors' maturation competence (the capacity to develop toward a fully functional state), but not their differentiation competence (the ability to evolve into transcriptomically diverse states). The underlying mechanism was chromatin priming, orchestrated by the transcription factor Nfib in collaboration with regulators of inhibitory neuron development. Finally, the heterochronic transplantation of progenitors 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 their maturation to achieve maximum adaptability. Overall design: Transcriptomic,barcode-lineage tracing and Chromatin acessibilty of developping mouse forebrain cell subtypes