Stem cell regionalization during olfactory bulb neurogenesis depends on regulatory interactions between Vax1 and Pax6
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.
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All data generated or analysed during this study are included in the manuscript
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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).
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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