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Cited by 111Neurogenesis and neuroplasticity mechanismsDevelopmental Biology and Gene RegulationSingle-cell and spatial transcriptomics

The development and evolution of inhibitory neurons in primate cerebrum

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Schmitz, Matthew T., Sandoval, Kadellyn, Chen, Christopher P., Mostajo-Radji, Mohammed A., Seeley, William W., Nowakowski, Tomasz J., Ye, Chun Jimmie, Paredes, Mercedes F. +1 more·2022·Nature
DOI 10.1038/s41586-022-04510-wPMC PMC8967711
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Abstract

Neuroanatomists have long speculated that expanded primate brains contain an increased morphological diversity of inhibitory neurons (INs) 1 , and recent studies have identified primate-specific neuronal populations at the molecular level 2 . However, we know little about the developmental mechanisms that specify evolutionarily novel cell types in the brain. Here, we reconstruct gene expression trajectories specifying INs generated throughout the neurogenic period in macaques and mice by analysing the transcriptomes of 250,181 cells. We find that the initial classes of INs generated prenatally are largely conserved among mammals. Nonetheless, we identify two contrasting developmental mechanisms for specifying evolutionarily novel cell types during prenatal development. First, we show that recently identified primate-specific TAC3 striatal INs are specified by a unique transcriptional programme in progenitors followed by induction of a distinct suite of neuropeptides and neurotransmitter receptors in new-born neurons. Second, we find that multiple classes of transcriptionally conserved olfactory bulb (OB)-bound precursors are redirected to expanded primate white matter and striatum. These classes include a novel peristriatal class of striatum laureatum neurons that resemble dopaminergic periglomerular cells of the OB. We propose an evolutionary model in which conserved initial classes of neurons supplying the smaller primate OB are reused in the enlarged striatum and cortex. Together, our results provide a unified developmental taxonomy of initial classes of mammalian INs and reveal multiple developmental mechanisms for neural cell type evolution.

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  • The LGE PAX6+ interneuron signature resembles mouse olfactory bulb precursors that generate neurons redirected to white matter in primates.

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References 62 · Cited by 111

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Authors
Schmitz, M. T., Sandoval, K., Chen, C. P., Mostajo-Radji, M. A., Seeley, W. W., Nowakowski, T. J., Ye, C. J., Paredes, M. F., & Pollen, A. A.
Affiliations
University of California, San Francisco (US)
Corresponding author
Pollen, Alex A.
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2022-03-23
Volume
603
Issue
7903
Pages
871-877
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/s41586-022-04510-w
PMC
PMC8967711
OpenAlex
W4221102696
Cited by
111
References
62
Citations by year
2026: 17 · 2025: 32 · 2024: 24 · 2023: 28 · 2022: 10
FWCI
8.61
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
  • Shurl and Kay Curci Foundation
  • Innovative Genomics Institute
  • National Institutes of Health
  • University of California, San Francisco
  • National Institute of Mental Health (RF1MH121268, DP2MH122400, U01MH114825)
  • National Institute of Allergy and Infectious Diseases (R01AI136972)
  • National Institute of Neurological Disorders and Stroke (F31NS124333, P01NS083513, DP2NS122550)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD007470)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
Keywords
inhibitory neurons, primate brain evolution, striatum, olfactory bulb, transcriptional programs, progenitor cells, macaque, mice, neurogenesis
MeSH terms
Animals, Corpus Striatum, Biological Evolution, Female, Macaca, Mammals, Neurons, Olfactory Bulb, Pregnancy, Primates, Embryonic Development, Mice, Neurogenesis, Dopaminergic Neurons

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