Developmental diversification of cortical inhibitory interneurons

Christian Mayer, Christoph Hafemeister, Rachel C. Bandler, Robert Machold, Renata Batista Brito, Xavier Jaglin, Kathryn Allaway, Andrew Butler, Gordon Fishell, Rahul Satija

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)457-462
Number of pages6
JournalNature
Volume555
Issue number7697
DOIs
StatePublished - Mar 22 2018

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Interneurons
Transcription Factors
RNA Sequence Analysis
Parvalbumins
Gene Regulatory Networks
Transcriptome
Seeds
Neurons
Brain

ASJC Scopus subject areas

  • General

Cite this

Mayer, C., Hafemeister, C., Bandler, R. C., Machold, R., Batista Brito, R., Jaglin, X., ... Satija, R. (2018). Developmental diversification of cortical inhibitory interneurons. Nature, 555(7697), 457-462. https://doi.org/10.1038/nature25999

Developmental diversification of cortical inhibitory interneurons. / Mayer, Christian; Hafemeister, Christoph; Bandler, Rachel C.; Machold, Robert; Batista Brito, Renata; Jaglin, Xavier; Allaway, Kathryn; Butler, Andrew; Fishell, Gordon; Satija, Rahul.

In: Nature, Vol. 555, No. 7697, 22.03.2018, p. 457-462.

Research output: Contribution to journalArticle

Mayer, C, Hafemeister, C, Bandler, RC, Machold, R, Batista Brito, R, Jaglin, X, Allaway, K, Butler, A, Fishell, G & Satija, R 2018, 'Developmental diversification of cortical inhibitory interneurons', Nature, vol. 555, no. 7697, pp. 457-462. https://doi.org/10.1038/nature25999
Mayer C, Hafemeister C, Bandler RC, Machold R, Batista Brito R, Jaglin X et al. Developmental diversification of cortical inhibitory interneurons. Nature. 2018 Mar 22;555(7697):457-462. https://doi.org/10.1038/nature25999
Mayer, Christian ; Hafemeister, Christoph ; Bandler, Rachel C. ; Machold, Robert ; Batista Brito, Renata ; Jaglin, Xavier ; Allaway, Kathryn ; Butler, Andrew ; Fishell, Gordon ; Satija, Rahul. / Developmental diversification of cortical inhibitory interneurons. In: Nature. 2018 ; Vol. 555, No. 7697. pp. 457-462.
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