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

研究成果: Article査読

44 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1604-1609
ページ数6
ジャーナルProceedings of the National Academy of Sciences of the United States of America
111
4
DOI
出版ステータスPublished - 2014 1月 28

ASJC Scopus subject areas

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