Mechanisms of neurogenesis and gliogenesis by neural stem cells

• Project Area: Neural Diversity and Neocortical Organization
• Project/Area Number: 22123004
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Keio University
• Principal Investigator: SHIMAZAKI Takuya 慶應義塾大学, 医学部, 准教授 (00324749)
• Project Period (FY): 2010-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥97,760,000 (Direct Cost: ¥75,200,000、Indirect Cost: ¥22,560,000); Fiscal Year 2014: ¥12,610,000 (Direct Cost: ¥9,700,000、Indirect Cost: ¥2,910,000); Fiscal Year 2013: ¥13,130,000 (Direct Cost: ¥10,100,000、Indirect Cost: ¥3,030,000); Fiscal Year 2012: ¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000); Fiscal Year 2011: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000); Fiscal Year 2010: ¥39,130,000 (Direct Cost: ¥30,100,000、Indirect Cost: ¥9,030,000)
• Keywords: 神経幹細胞 / 神経細胞 / グリア / 分化 / 転写因子 / Coup-TFI/II / miRNA / p38MAP-kinase / NFIA / 神経 / 転写制御因子 / ES細胞

Outline of Final Research Achievements

We have explored novel factors which are integrated in the molecular machinery responsible for neurogenic-to-gliogenic transition of neural stem cells (NSCs) downstream of and in parallel with transcription factors Coup-TFI/II which are triggers of this transition. 1) We identified a miRNA family miR-17/106 as novel key regulators of the transition through downregulation of p38 MAP-Kinase downstream of Coup-TFI/II. 2) We found that the miR-153 mediated fine control of expressions of NFIA/B which are essential for gliogenesis is important in the molecular networks that regulate the timing of gliogenesis by NSCs in the developing CNS.

Research Products

• [Journal Article] The miR-17/106-p38 axis is a key regulator of the neurogenic-to-gliogenic transition in developing neural stem/progenitor cells (2014)
  • Author(s): Hayato Naka-Kanedaa, Shiho Nakamuraa, Mana Igarashi, Hisashi Aoid, Hiroaki K ankib, Jun Tsuyama, Shuichi Tsutsumie, Hiroyuki Aburatanie, Takuya Shimazakib, and Hideyuki Okano.
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 111(4) Issue: 4 Pages: 1604-1609
  • DOI: 10.1073/pnas.1315567111
  • Peer Reviewed
• [Journal Article] LIM homeobox 8 (Lhx8) is a key regulator of the cholinergic neuronal function via a tropomyosin receptor kinase A (TrkA)-mediated positive feedback loop. (2014)
  • Author(s): Tomioka T, Shimazaki T, Yamauchi T, Oki T, Ohgoh M, Okano H
  • Journal Title: J Biol Chem Volume: 289 Issue: 2 Pages: 1000-1010
  • DOI: 10.1074/jbc.m113.494385
  • Peer Reviewed
• [Journal Article] FRS2α regulates Erk levels to control a self-renewal target Hes1 and proliferation of FGF-responsive neural stem/progenitor cells. (2010)
  • Author(s): Sato T, et al.
  • Journal Title: Stem Cells Volume: 33 Pages: 1661-1673
  • Peer Reviewed
• [Journal Article] Regulation of adult neural progenitor cells by Galectin-1/beta1 Integrin interaction. (2010)
  • Author(s): Sakaguchi M, et al.
  • Journal Title: J Neurochem. Volume: 113 Pages: 1516-1524
  • Peer Reviewed
• [Presentation] 神経幹細胞のグリア分化能を制御する発生時期特異的な因子の同定 (2015)
  • Author(s): 津山 淳、 Jens Bunt、 Linda J. Richards、岩成 宏子、 望月康弘、浜窪 隆雄、島崎 琢也、岡野 栄之
  • Organizer: 第14回日本再生医療学会総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2015-03-19
• [Remarks] 新しい神経幹細胞の制御法によって神経産生能の回復に成功
  • URL: http://www.keio.ac.jp/ja/press_release/2013/kr7a4300000cyziu.html
• [Remarks]
  • URL: http://www.okano-lab.com