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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Author details
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
- Stephen Liberles, Harvard Medical School, United States
Publication history
- Received: April 24, 2020
- Accepted: August 6, 2020
- Accepted Manuscript published: August 7, 2020 (version 1)
- 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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Further reading
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- Developmental Biology
- Evolutionary Biology
Development of tooth shape is regulated by the enamel knot signalling centre, at least in mammals. Fgf signalling regulates differential proliferation between the enamel knot and adjacent dental epithelia during tooth development, leading to formation of the dental cusp. The presence of an enamel knot in non-mammalian vertebrates is debated given differences in signalling. Here, we show the conservation and restriction of fgf3, fgf10, and shh to the sites of future dental cusps in the shark (Scyliorhinus canicula), whilst also highlighting striking differences between the shark and mouse. We reveal shifts in tooth size, shape, and cusp number following small molecule perturbations of canonical Wnt signalling. Resulting tooth phenotypes mirror observed effects in mammals, where canonical Wnt has been implicated as an upstream regulator of enamel knot signalling. In silico modelling of shark dental morphogenesis demonstrates how subtle changes in activatory and inhibitory signals can alter tooth shape, resembling developmental phenotypes and cusp shapes observed following experimental Wnt perturbation. Our results support the functional conservation of an enamel knot-like signalling centre throughout vertebrates and suggest that varied tooth types from sharks to mammals follow a similar developmental bauplan. Lineage-specific differences in signalling are not sufficient in refuting homology of this signalling centre, which is likely older than teeth themselves.
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- Developmental Biology
- Evolutionary Biology
The tooth shape of sharks and mice are regulated by a similar signaling center despite their teeth having very different geometries.