The miR-17/106-p38 axis is a key regulator of the neurogenic-to-gliogenic transition in developing neural stem/progenitor cells

Hayato Naka-Kaneda, Shiho Nakamura, Mana Igarashi, Hisashi Aoi, Hiroaki Kanki, Jun Tsuyama, Shuichi Tsutsumi, Hiroyuki Aburatani, Takuya Shimazaki, Hideyuki Okano

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Neural stem/progenitor cell (NSPC) multipotency is highly regulated so that specific neural networks form during development. NSPCs cannot respond to gliogenic signals without acquiring gliogenic competence and decreasing their neurogenic competence as development proceeds. Coup-tfI and Coup-tfII are triggers of these temporal NSPC competence changes. However, the downstream effectors of Coup-tfs that mediate the neurogenic-togliogenic competence transition remain unknown. Here, we identified the microRNA-17/106 (miR-17/106)-p38 axis as a critical regulator of this transition. Overexpression of miR-17 inhibited the acquisition of gliogenic competence and forced stage-progressed NSPCs to regain neurogenic competence without altering the methylation status of a glial gene promoter. We also identified Mapk14 (also known as p38) as a target of miR-17/106 and found that Mapk14 inhibition restored neurogenic competence after the neurogenic phase. These results demonstrate that the miR-17/106- p38 axis is a key regulator of the neurogenic-to-gliogenic NSPC competence transition and that manipulation of this axis permits bidirectional control of NSPC multipotency.

Original languageEnglish
Pages (from-to)1604-1609
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number4
DOIs
Publication statusPublished - 2014 Jan 28

Keywords

  • Differentiation
  • Fate determination
  • Glia
  • Neural development
  • Neurogenesis

ASJC Scopus subject areas

  • General

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