Stem cell regionalization during olfactory bulb neurogenesis depends on regulatory interactions between Vax1 and Pax6

  1. Nathalie Coré  Is a corresponding author
  2. Andrea Erni
  3. Hanne M Hoffmann
  4. Pamela L Mellon
  5. Andrew J Saurin
  6. Christophe Béclin
  7. Harold Cremer  Is a corresponding author
  1. Aix-Marseille University, CNRS, France
  2. University of California San Diego, United States

Abstract

Different subtypes of interneurons, destined for the olfactory bulb, are continuously generated by neural stem cells located in the ventricular and subventricular zones along the lateral forebrain ventricles of mice. Neuronal identity in the olfactory bulb depends on the existence of defined microdomains of pre-determined neural stem cells along the ventricle walls. The molecular mechanisms underlying positional identity of these neural stem cells are poorly understood. Here we show that the transcription factor Vax1 controls the production of two specific neuronal sub-types. First, it is directly necessary to generate Calbindin expressing interneurons from ventro-lateral progenitors. Second, it represses the generation of dopaminergic neurons by dorsolateral progenitors through inhibition of Pax6 expression. We present data indicating that this repression occurs, at least in part, via activation of microRNA miR-7.

Data availability

All data generated or analysed during this study are included in the manuscript

Article and author information

Author details

  1. Nathalie Coré

    IBDM, Developmental Biology Institute of Marseille, Aix-Marseille University, CNRS, Marseille, France
    For correspondence
    nathalie.core@univ-amu.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3865-4539
  2. Andrea Erni

    IBDM, Developmental Biology Institute of Marseille, Aix-Marseille University, CNRS, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Hanne M Hoffmann

    Department of Obstetrics, Gynecology, and Reproductive Sciences and the Center for Reproductive Science and Medicine, University of California San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Pamela L Mellon

    Department of Obstetrics, Gynecology, and Reproductive Sciences and the Center for Reproductive Science and Medicine, University of California San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Andrew J Saurin

    IBDM, Aix-Marseille University, CNRS, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Christophe Béclin

    IBDM, Developmental Biology Institute of Marseille, Aix-Marseille University, CNRS, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Harold Cremer

    IBDM, Developmental Biology Institute of Marseille, Aix-Marseille University, CNRS, Marseille, France
    For correspondence
    harold.cremer@univ-amu.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8673-5176

Funding

Agence Nationale de la Recherche (13-BSV4-0013)

  • Nathalie Coré
  • Christophe Béclin
  • Harold Cremer

National Institutes of Health (P42 ES010337)

  • Pamela L Mellon

National Institutes of Health (K99 HD084759)

  • Hanne M Hoffmann

Swiss National Science Foundation (P2BSP3_175013)

  • Andrea Erni

Agence Nationale de la Recherche (17-CE16-0025)

  • Nathalie Coré
  • Christophe Béclin
  • Harold Cremer

Fondation de France (FDF70959)

  • Nathalie Coré
  • Christophe Béclin
  • Harold Cremer

Fondation pour la Recherche Médicale (EQU201903007806)

  • Nathalie Coré
  • Christophe Béclin
  • Harold Cremer

National Institutes of Health (P50 HD12303)

  • Pamela L Mellon

National Institutes of Health (R01 HD072754)

  • Pamela L Mellon

National Institutes of Health (R01 HD082567)

  • Pamela L Mellon

National Institutes of Health (P30 CA23100)

  • Pamela L Mellon

National Institutes of Health (P30 DK063491)

  • Pamela L Mellon

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

Ethics

Animal experimentation: All animal procedures were carried out in accordance to the European Communities Council Directie 2010/63/EU and approved by French ethical committees (Comité d'Ethique pour l'expérimentation animale no. 14; permission numbers: 00967.03; 2017112111116881v2).

Reviewing Editor

  1. Stephen Liberles, Harvard Medical School, United States

Publication history

  1. Received: April 24, 2020
  2. Accepted: August 6, 2020
  3. Accepted Manuscript published: August 7, 2020 (version 1)
  4. Version of Record published: August 20, 2020 (version 2)

Copyright

© 2020, Coré 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. Nathalie Coré
  2. Andrea Erni
  3. Hanne M Hoffmann
  4. Pamela L Mellon
  5. Andrew J Saurin
  6. Christophe Béclin
  7. Harold Cremer
(2020)
Stem cell regionalization during olfactory bulb neurogenesis depends on regulatory interactions between Vax1 and Pax6
eLife 9:e58215.
https://doi.org/10.7554/eLife.58215

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