PUBLICATION

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

Authors
Katz, S., Cussigh, D., Urbán, N., Blomfield, I., Guillemot, F., Bally-Cuif, L., Coolen, M.
ID
ZDB-PUB-161027-1
Date
2016
Source
Cell Reports   17: 1383-1398 (Journal)
Registered Authors
Bally-Cuif, Laure, Coolen, Marion, Cussigh, Delphine, Katz, Shauna
Keywords
Argonaute, Notch, adult neurogenesis, miR-9, neural stem cell, quiescence, radial glia, telencephalon, zebrafish
MeSH Terms
  • Aging/metabolism
  • Animals
  • Argonaute Proteins/metabolism
  • Cell Cycle*
  • Cell Nucleus/metabolism
  • Gene Expression Regulation
  • Mice
  • MicroRNAs/genetics
  • MicroRNAs/metabolism*
  • Models, Biological
  • Neural Stem Cells/cytology*
  • Neural Stem Cells/metabolism*
  • Neuroglia/metabolism
  • Receptors, Notch/metabolism
  • Signal Transduction
  • Telencephalon/metabolism
  • Zebrafish/genetics*
  • Zebrafish/metabolism
PubMed
27783951 Full text @ Cell Rep.
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.
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