title: A Nuclear Role for miR-9 and Argonaute Proteins in Balancing Quiescent and Activated Neural Stem Cell States.
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.
authors: 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.
authors: Shauna
authors: S
authors: Katz
authors: 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.
authors: Delphine
authors: D
authors: Cussigh
authors: Mill Hill Laboratory, The Francis Crick Institute, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors: Noelia
authors: N
authors: Urbán
authors: Mill Hill Laboratory, The Francis Crick Institute, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors: Isabelle
authors: I
authors: Blomfield
authors: Mill Hill Laboratory, The Francis Crick Institute, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors: François
authors: F
authors: Guillemot
authors: 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.
authors: Laure
authors: L
authors: Bally-Cuif
authors: 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.
authors: Marion
authors: M
authors: Coolen
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D060565:Argonaute Proteins / Q000378:metabolism; D002453:Cell Cycle; D002467:Cell Nucleus / Q000378:metabolism; D005786:Gene Expression Regulation; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D013687:Telencephalon / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics* / Q000378:metabolism
chemical_list: C526735:Ago2 protein, mouse; D060565:Argonaute Proteins; C551804:MIRN9 microRNA, mouse; C573942:MIRN9 microRNA, zebrafish; D035683:MicroRNAs; D051880:Receptors, Notch
keywords: Argonaute; Notch; adult neurogenesis; miR-9; neural stem cell; quiescence; radial glia; telencephalon; zebrafish