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Cell Rep. 2016 Oct 25;17(5):1383-1398. doi: 10.1016/j.celrep.2016.09.088.

A Nuclear Role for miR-9 and Argonaute Proteins in Balancing Quiescent and Activated Neural Stem Cell States.

Author information

1
Zebrafish Neurogenetics Group, Paris-Saclay Institute of Neuroscience (Neuro-PSI), UMR 9197, CNRS-University Paris-Sud, Avenue de la Terrasse, 91190 Gif-sur-Yvette, France.
2
Zebrafish Neurogenetics Group, Paris-Saclay Institute of Neuroscience (Neuro-PSI), UMR 9197, CNRS-University Paris-Sud, Avenue de la Terrasse, 91190 Gif-sur-Yvette, France; Department of Developmental and Stem Cell Biology, Institut Pasteur and CNRS UMR 3738, 25 rue du Dr Roux, 75015 Paris, France.
3
Mill Hill Laboratory, The Francis Crick Institute, The Ridgeway, Mill Hill, London NW7 1AA, UK.
4
Zebrafish Neurogenetics Group, Paris-Saclay Institute of Neuroscience (Neuro-PSI), UMR 9197, CNRS-University Paris-Sud, Avenue de la Terrasse, 91190 Gif-sur-Yvette, France; Department of Developmental and Stem Cell Biology, Institut Pasteur and CNRS UMR 3738, 25 rue du Dr Roux, 75015 Paris, France. Electronic address: laure.bally-cuif@pasteur.fr.
5
Zebrafish Neurogenetics Group, Paris-Saclay Institute of Neuroscience (Neuro-PSI), UMR 9197, CNRS-University Paris-Sud, Avenue de la Terrasse, 91190 Gif-sur-Yvette, France; Department of Developmental and Stem Cell Biology, Institut Pasteur and CNRS UMR 3738, 25 rue du Dr Roux, 75015 Paris, France. Electronic address: marion.coolen@pasteur.fr.

Abstract

Throughout life, adult neural stem cells (NSCs) produce new neurons and glia that contribute to crucial brain functions. Quiescence is an essential protective feature of adult NSCs; however, the establishment and maintenance of this state remain poorly understood. We demonstrate that in the adult zebrafish pallium, the brain-enriched miR-9 is expressed exclusively in a subset of quiescent NSCs, highlighting a heterogeneity within these cells, and is necessary to maintain NSC quiescence. Strikingly, miR-9, along with Argonaute proteins (Agos), is localized to the nucleus of quiescent NSCs, and manipulating their nuclear/cytoplasmic ratio impacts quiescence. Mechanistically, miR-9 permits efficient Notch signaling to promote quiescence, and we identify the RISC protein TNRC6 as a mediator of miR-9/Agos nuclear localization in vivo. We propose a conserved non-canonical role for nuclear miR-9/Agos in controlling the balance between NSC quiescence and activation, a key step in maintaining adult germinal pools.

KEYWORDS:

Argonaute; Notch; adult neurogenesis; miR-9; neural stem cell; quiescence; radial glia; telencephalon; zebrafish

PMID:
27783951
PMCID:
PMC5098119
DOI:
10.1016/j.celrep.2016.09.088
[Indexed for MEDLINE]
Free PMC Article

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