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Nature DOI:10.1038/nature25999

Developmental diversification of cortical inhibitory interneurons.

Publication TypeJournal Article
Year of Publication2018
AuthorsMayer, C, Hafemeister, C, Bandler, RC, Machold, R, Brito, RBatista, Jaglin, X, Allaway, K, Butler, A, Fishell, G, Satija, R
Date Published2018 03 22
KeywordsAnimals, Cell Differentiation, Embryo, Mammalian, Female, Ganglia, Gene Expression Profiling, Humans, Interneurons, Male, MEF2 Transcription Factors, Mice, Mitosis, Neural Inhibition, Parvalbumins, RNA, Small Cytoplasmic, Single-Cell Analysis, Visual Cortex

Diverse subsets of cortical interneurons have vital roles in higher-order brain functions. To investigate how this diversity is generated, here we used single-cell RNA sequencing to profile the transcriptomes of mouse cells collected along a developmental time course. 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 time points, we identified shared sources of transcriptomic heterogeneity between adult interneurons and their precursors, and uncovered the embryonic emergence of cardinal interneuron subtypes. Our analysis revealed that the transcription factor Mef2c, which is linked to various neuropsychiatric and neurodevelopmental disorders, delineates early precursors of parvalbumin-expressing neurons, 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 interneuron subtypes.


Alternate JournalNature
PubMed ID29513653
PubMed Central IDPMC6052457
Grant ListR01 NS039007 / NS / NINDS NIH HHS / United States
P01 NS074972 / NS / NINDS NIH HHS / United States
R01 MH071679 / MH / NIMH NIH HHS / United States
T32 GM007308 / GM / NIGMS NIH HHS / United States
DP2 HG009623 / HG / NHGRI NIH HHS / United States
F30 MH114462 / MH / NIMH NIH HHS / United States
R01 NS081297 / NS / NINDS NIH HHS / United States
R01 MH111529 / MH / NIMH NIH HHS / United States