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

Shauna Katz (1) , Delphine Cussigh (1, 2) , Noelia Urbán (3) , Isabelle Maria Blomfield (3) , François Guillemot (3) , Laure Bally-Cuif (1, 2) , Marion Coolen (1, 2)

1 NeuroPSI - Institut des Neurosciences Paris-Saclay
2 CNRS UMR3738 - Biologie du Développement et Cellules souches (Département)
3 The Francis Crick Institute [London]

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

Domains: Life Sciences [q-bio]

Shauna Katz, Delphine Cussigh, Noelia Urbán, Isabelle Maria Blomfield, François Guillemot, et al.. A Nuclear Role for miR-9 and Argonaute Proteins in Balancing Quiescent and Activated Neural Stem Cell States. Cell Reports, 2016, 17 (5), pp.1383-1398. ⟨10.1016/j.celrep.2016.09.088⟩. ⟨pasteur-02399124⟩