Summary
Diverse subsets of cortical interneurons play vital roles in higher-order
brain functions. To investigate how this diversity is generated, we used single
cell RNA-seq to profile the transcriptomes of murine cells collected along a
developmental timecourse. Heterogeneity within mitotic progenitors in the
ganglionic eminences is driven by a highly conserved maturation trajectory,
alongside eminence-specific transcription factor expression that seeds the
emergence of later diversity. Upon becoming postmitotic, progenitors diverge and
differentiate into transcriptionally distinct states, including an interneuron
precursor state. By integrating datasets across developmental timepoints, we
identified shared sources of transcriptomic heterogeneity between adult
interneurons and their precursors, revealing the embryonic emergence of
interneuron cardinal subtypes. Our analysis revealed that the ASD-associated
transcription factor Mef2c delineates early Pvalb-precursors, and is essential
for their development. These findings shed new light on the molecular
diversification of early inhibitory precursors, and identify gene modules that
may influence the specification of human subtypes.
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