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Developmental diversification of cortical inhibitory interneurons

Author

Listed:
  • Christian Mayer

    (NYU Neuroscience Institute, Langone Medical Center
    New York Genome Center
    Harvard Medical School
    Broad Institute, Stanley Center for Psychiatric Research)

  • Christoph Hafemeister

    (New York Genome Center)

  • Rachel C. Bandler

    (NYU Neuroscience Institute, Langone Medical Center)

  • Robert Machold

    (NYU Neuroscience Institute, Langone Medical Center)

  • Renata Batista Brito

    (NYU Neuroscience Institute, Langone Medical Center
    Albert Einstein College of Medicine)

  • Xavier Jaglin

    (NYU Neuroscience Institute, Langone Medical Center
    Harvard Medical School)

  • Kathryn Allaway

    (NYU Neuroscience Institute, Langone Medical Center
    Harvard Medical School)

  • Andrew Butler

    (New York Genome Center
    Center for Genomics and Systems Biology, New York University)

  • Gord Fishell

    (NYU Neuroscience Institute, Langone Medical Center
    Harvard Medical School
    Broad Institute, Stanley Center for Psychiatric Research
    Center for Genomics and Systems Biology, New York University)

  • Rahul Satija

    (New York Genome Center
    Center for Genomics and Systems Biology, New York University)

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.

Suggested Citation

  • Christian Mayer & Christoph Hafemeister & Rachel C. Bandler & Robert Machold & Renata Batista Brito & Xavier Jaglin & Kathryn Allaway & Andrew Butler & Gord Fishell & Rahul Satija, 2018. "Developmental diversification of cortical inhibitory interneurons," Nature, Nature, vol. 555(7697), pages 457-462, March.
  • Handle: RePEc:nat:nature:v:555:y:2018:i:7697:d:10.1038_nature25999
    DOI: 10.1038/nature25999
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    10. Christopher T. Rhodes & Joyce J. Thompson & Apratim Mitra & Dhanya Asokumar & Dongjin R. Lee & Daniel J. Lee & Yajun Zhang & Eva Jason & Ryan K. Dale & Pedro P. Rocha & Timothy J. Petros, 2022. "An epigenome atlas of neural progenitors within the embryonic mouse forebrain," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    11. David Morizet & Isabelle Foucher & Alessandro Alunni & Laure Bally-Cuif, 2024. "Reconstruction of macroglia and adult neurogenesis evolution through cross-species single-cell transcriptomic analyses," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    12. Wendy Xueyi Wang & Julie L. Lefebvre, 2022. "Morphological pseudotime ordering and fate mapping reveal diversification of cerebellar inhibitory interneurons," Nature Communications, Nature, vol. 13(1), pages 1-21, December.

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