Maf and Mafb control mouse pallial interneuron fate and maturation through neuropsychiatric disease gene regulation

Abstract

Maf (c-Maf) and Mafb transcription factors (TFs) have compensatory roles in repressing somatostatin (SST+) interneuron (IN) production in medial ganglionic eminence (MGE) secondary progenitors in mice. Maf and Mafb conditional deletion (cDKO) decreases the survival of MGE-derived cortical interneurons (CINs) and changes their physiological properties. Herein, we show that (1) Mef2c and Snap25 are positively regulated by Maf and Mafb to drive IN morphological maturation; (2) Maf and Mafb promote Mef2c expression which specifies parvalbumin (PV+) INs; (3) Elmo1, Igfbp4 and Mef2c are candidate markers of immature PV+ hippocampal INs (HIN). Furthermore, Maf/Mafb neonatal cDKOs have decreased CINs and increased HINs, that express Pnoc, an HIN specific marker. Our findings not only elucidate key gene targets of Maf and Mafb that control IN development, but also identify for the first time TFs that differentially regulate CIN vs. HIN production.

Data availability

We submitted the original source data that was used for Seurat pipeline analysis to GEO under the accession number GSE144222. Readers can utilize these datasets for reanalysis and new analysis using Seurat pipeline or other customized codes for more data mining.

The following data sets were generated

Article and author information

Author details

  1. Emily Ling-Lin Pai

    Psychiatry, University of California, San Francisco, San Francisco, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6967-5239
  2. Jin Chen

    Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States
    Competing interests
    No competing interests declared.
  3. Siavash Fazel Darbandi

    Psychiatry, University of California, San Francisco, San Francisco, United States
    Competing interests
    No competing interests declared.
  4. Frances S Cho

    Neurology, University of California, San Francisco, San Francisco, United States
    Competing interests
    No competing interests declared.
  5. Jiapei Chen

    Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, United States
    Competing interests
    No competing interests declared.
  6. Susan Lindtner

    Psychiatry, University of California, San Francisco, San Francisco, United States
    Competing interests
    No competing interests declared.
  7. Julia S Chu

    Neurology, University of California, San Francisco, San Francisco, United States
    Competing interests
    No competing interests declared.
  8. Jeanne Paz

    Neuroscience Graduate Program, University of California, San Francisco, San Francisco, United States
    Competing interests
    No competing interests declared.
  9. Daniel Vogt

    Pediatrics and Human Development, Michigan State University, Grand Rapids, United States
    Competing interests
    No competing interests declared.
  10. Mercedes F Paredes

    Department of Neurological Surgery, University of California, San Francisco, San Francisco, United States
    Competing interests
    No competing interests declared.
  11. John LR Rubenstein

    Department of Psychiatry, University of California, San Francisco, San Francisco, United States
    For correspondence
    John.rubenstein@ucsf.edu
    Competing interests
    John LR Rubenstein, is cofounder, stockholder, and currently on the scientific board of Neurona, a company studying the potential therapeutic use of interneuron transplantation.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4414-7667

Funding

National Institute of Mental Health (MH081880)

  • Emily Ling-Lin Pai
  • John LR Rubenstein

National Science Foundation (1608236)

  • Frances S Cho
  • Jeanne Paz

National Science Foundation (1144247)

  • Frances S Cho

NIH Office of the Director (F31 NS111819-01A1)

  • Frances S Cho

National Institute of Mental Health (MH049428)

  • John LR Rubenstein

National Institute of Diabetes and Digestive and Kidney Diseases (P30DK098722)

  • Emily Ling-Lin Pai
  • John LR Rubenstein

NIH Office of the Director (GM134154)

  • Jin Chen

National Institute of Neurological Disorders and Stroke (NS34661)

  • Siavash Fazel Darbandi
  • John LR Rubenstein

Simons Foundation (SFARI A133320)

  • Siavash Fazel Darbandi
  • John LR Rubenstein

National Institute of Neurological Disorders and Stroke (K08NS091537)

  • Julia S Chu
  • Mercedes F Paredes

Spectrum Health-MSU Alliance Corporation

  • Daniel Vogt

National Institute of Neurological Disorders and Stroke (R01NS096369)

  • Frances S Cho
  • Jiapei Chen
  • Jeanne Paz

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Joseph G Gleeson, Howard Hughes Medical Institute, The Rockefeller University, United States

Ethics

Animal experimentation: All procedures and animal care were approved and performed in accordance with the University of California San Francisco Laboratory Animal Research Center (LARC) guidelines. All animals were handled based on the approved institutional animal care and use committee (IACUC) protocol (AN180174-01B) at the University of California San Francisco.

Version history

  1. Received: January 6, 2020
  2. Accepted: May 22, 2020
  3. Accepted Manuscript published: May 26, 2020 (version 1)
  4. Version of Record published: June 9, 2020 (version 2)

Copyright

© 2020, Pai et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Emily Ling-Lin Pai
  2. Jin Chen
  3. Siavash Fazel Darbandi
  4. Frances S Cho
  5. Jiapei Chen
  6. Susan Lindtner
  7. Julia S Chu
  8. Jeanne Paz
  9. Daniel Vogt
  10. Mercedes F Paredes
  11. John LR Rubenstein
(2020)
Maf and Mafb control mouse pallial interneuron fate and maturation through neuropsychiatric disease gene regulation
eLife 9:e54903.
https://doi.org/10.7554/eLife.54903

Share this article

https://doi.org/10.7554/eLife.54903

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