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Paradigm shift in brain formation research

開催日 2014/9/13
時間 15:00 - 17:00
会場 Room D(503)
Chairperson(s) 河崎 洋志 / Hiroshi Kawasaki (金沢大学医薬保健研究域 脳・肝インターフェースメディシン研究センター分子神経科学部門 / Department of Biophysical Genetics, Graduate School of Medical Sciences, Kanazawa University, Japan)
松﨑 文雄 / Fumio Matsuzaki (理化学研究所 発生・再生科学総合研究センター / Laboratory for Cell Asymmetry, RIKEN Center for Developmental Biology, Japan)

Dynamic control of bHLH factors in multipotency and fate choice of neural stem cells

  • S3-D-1-1
  • 影山 龍一郎 / Ryoichiro Kageyama:1,2,3 
  • 1:京都大・ウイルス研 / Insti Virus Res, Kyoto Univ, Kyoto, Japan 2:京都大・物質ー細胞統合システム拠点 / WPI-iCeMS, Kyoto Univ, Kyoto, Japan 3:JST-CREST / JST-CREST, Saitama, Japan 

During brain development, neural stem cells gradually change their competency, giving rise to various types of neurons first and glial cells later. It is thus very important to maintain neural stem cells until the final stage of development to generate a full diversity of cell types. We found that expression of the basic helix-loop-helix (bHLH) factor Hes1 oscillates in neural stem cells, and that Hes1 oscillation drives the cyclic expression of proneural factors such as Ascl1/Mash1. During neuronal differentiation, Hes1 expression disappears and proneural factor expression becomes sustained. By contrast, during astrocyte differentiation, Hes1 expression becomes dominant while proneural factor expression disappears. These results suggest that the multipotency is a state controlled by multiple oscillating fate-determination factors, and that one of them becomes dominant during fate choice. We further showed by optogenetic approach that sustained expression of Ascl1 promotes neuronal differentiation, whereas oscillatory expression of Ascl1 activates proliferation of neural stem cells, indicating that the expression dynamics is important for the function of Ascl1. We now examine the dynamics of Hes1 and Ascl1 in the adult brain and will discuss how these factors regulate adult neurogenesis.

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