Contributors: Institut des Neurosciences Paris-Saclay (NeuroPSI); Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS); Département de Biologie du Développement et Cellules souches - Department of Developmental and Stem Cell Biology; Institut Pasteur Paris; The Francis Crick Institute London; Work in the L.B.-C. lab was funded by the EU project ZF-Health (FP7/2010-2015 grant agreement 242048), the ANR (grant ANR-2012-BSV4-0004-01), the Ecole des Neurosciences de Paris (ENP), the FRM (FRP “Equipe” DEQ20120323692), and the European Research Council (AdG 322936). M.C. is supported by INSERM. S.K. was recipient of fellowships from the ENP, the DIM Cerveau et Pensée of Région Ile de France, and The Company of Biologists Limited (Travelling Fellowship DEVTF-140404). N.U. was supported by the BBSRC (BB/K005316/1). Work in F.G.’s lab was supported by The Francis Crick Institute that receives its core funding from Cancer Research UK (FC001089), the UK Medical Research Council (FC001089), and the Wellcome Trust (FC001089).; We thank members of the ZEN lab and Eric Miska for their critical input. We are grateful to J. Ninkovic for the 4C4 antibody.; ANR-12-BSV4-0004,HOMEOSTEM,Contrôle moléculaire et cellulaire de l'homéostasie des zones germinatives dans le télencéphale adulte chez le poisson zébré(2012); European Project: 242048,EC:FP7:HEALTH,FP7-HEALTH-2009-two-stage,ZF-HEALTH(2010); European Project: 322936,EC:FP7:ERC,ERC-2012-ADG_20120314,SYSTEMATICS(2013)
نبذة مختصرة : International audience ; 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.
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