Cited by 550Neurogenesis and neuroplasticity mechanismsSingle-cell and spatial transcriptomicsDevelopmental Biology and Gene Regulation

The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index; none of the 24 sources its claims cite is checked for support yet.

Developmental diversification of cortical inhibitory interneurons

Open access

Published version of a preprint

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.

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Crossref · 10.1038/nature25999

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    The genetic programs that drive interneuron fate specification and maintenance are not well understood.

    “the genetic programs driving interneuron fate specification and maintenance are not well understood”
  • The paper relies on this without support.

    It remains unclear how early sources of heterogeneity generate the vast diversity of adult interneurons.

    “it remains unclear how these early sources of heterogeneity generate the vast diversity of adult interneurons”
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Metadata

Authors
Mayer, C., Hafemeister, C., Bandler, R. C., Machold, R., Batista Brito, R., Jaglin, X., Allaway, K., Butler, A., Fishell, G., & Satija, R.
Affiliations
  • Broad Institute (US)
  • New York Genome Center (US)
  • NYU Langone Health (US)
  • Harvard University (US)
Corresponding author
  • Fishell, Gord
  • Satija, Rahul
Venue
Nature
Published
2018-03-05
Volume
555
Issue
7697
Pages
457-462
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2791731597
Cited by
492
References
42
Citations by year
2026: 39 · 2025: 43 · 2024: 50 · 2023: 53 · 2022: 65 · 2021: 76 · 2020: 73 · 2019: 59 · 2018: 34
FWCI
22.24
Type
journal article
Language
en
Open access
Locations
  • Nature (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • National Science Foundation (1342536)
  • Simons Foundation (P01 NS074972)
  • Deutsche Forschungsgemeinschaft
  • National Institutes of Health (NIH DP2, 1dp2hg009623-01, MH071679, NS074972)
  • National Institute of Mental Health (F30MH114462, R01MH111529, R01MH071679, R37MH071679)
  • National Human Genome Research Institute (DP2-HG-009623)
  • National Institute of General Medical Sciences (T32GM007308)
  • National Institute of Neurological Disorders and Stroke (P01NS074972, F31NS103398, R01NS039007, R01NS081297)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
cortical interneurons, MEF2C, parvalbumin neurons, ganglionic eminence, transcriptional heterogeneity, interneuron subtypes, developmental trajectories, transcription factors, neuropsychiatric disorders, mouse embryo
MeSH terms
Animals, Cell Differentiation, Embryo, Mammalian, Female, Ganglia, Humans, Interneurons, Male, Mitosis, Neural Inhibition, Parvalbumins, Visual Cortex, RNA, Small Cytoplasmic, Gene Expression Profiling, Mice, Single-Cell Analysis, MEF2 Transcription Factors

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