Early emergence of cortical interneuron diversity in the mouse embryo

GABAergic interneurons play crucial roles in the regulation of neural circuit activity in the cerebral cortex. A hallmark of cortical interneurons is their remarkable structural and functional diversity, yet the molecular determinants and the precise timing underlying their diversification remain largely unknown. Here we use single-cell transcriptomics to identify distinct types of progenitor cells and newborn neurons in the ganglionic eminences, the embryonic proliferative regions that give rise to cortical interneurons. These embryonic precursors define temporally and spatially restricted transcriptional trajectories that unambiguously relate to specific classes of interneurons in the adult cerebral cortex. Our findings therefore suggest that interneuron diversity is already patent shortly after neurons become postmitotic through the acquisition of specific transcriptional programs that unfold over several weeks in the developing cortex Mouse embryos were isolated at E12.5 and E14.5 from timed pregnant CD1 female mice. The dorsal MGE (dMGE), ventral MGE (vMGE) and caudal ganglionic eminence (CGE) regions were dissected. Cells were captured with small-sized (5-10 µm) RNA-seq IFCs using the Fluidigm C1 system. Libraries of single cells pooled from each C1 IFC were denatured and HiSeq flow cell was run for 100 cycles using a single-read recipe.