Elucidation of molecular mechanisms underlying a novel Olig2 binding factor-mediated oligodendrocyte differentiation

• Project/Area Number: 15K18373
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Niigata University
• Principal Investigator: Bizen Norihisa 新潟大学, 医歯学系, 助教 (40751053)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: オリゴデンドロサイト / Olig2 / 転写因子 / p53 / 神経幹細胞 / ノックアウトマウス / DNA損傷 / 細胞増殖 / 細胞死 / ミエリン / 分化促進 / 脱髄疾患

Outline of Final Research Achievements

We identified a novel Olig2 binding factor, Obp2 and analyzed central nervous system-specific Obp2 mutant mice. These mice exhibited severe loss of oligodendrocyte differentiation without motor neuron defects.We further found that Obp2 contributed to the maintenance of Olig2-positive neural precursor cells and oligodendrocyte progenitor cells through the regulation of DNA damage-p53 axis in central nervous system.
We also demonstrated that OIF, which is a truncated form of Obp2 strongly induced the transcriptional activity of oligodendrocyte related genes such as PLP and MBP, and promoted oligodendrocyte differentiation in dysmyelinating mice.
In conclusion, we suggest that Obp2 is indispensable for oligodendrocyte development and OIF could be useful for the therapy of demyelinating diseases.

Research Products

• [Journal Article] Endoplasmic reticulum-localized transmembrane protein Dpy19L1 is required for neurite outgrowth. (2016)
  • Author(s): Watanabe K, Bizen N, Sato N, Takebayashi H
  • Journal Title: PLOS ONE Volume: 11 Issue: 12 Pages: e0167985-e0167985
  • DOI: 10.1371/journal.pone.0167985
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Biallelic Variants in UBA5 Link Dysfunctional UFM1 Ubiquitin-like Modifier Pathway to Severe Infantile-Onset Encephalopathy. (2016)
  • Author(s): Muona M, Ishimura R, Laari A,...... , Komatsu M.
  • Journal Title: Am J Hum Genet. Volume: 99 Issue: 3 Pages: 683-94
  • DOI: 10.1016/j.ajhg.2016.06.020
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A synthetic polymer scaffold reveals the self-maintenance strategies of rat glioma stem cells by organization of the advantageous niche. (2016)
  • Author(s): Tabu K, Muramatsu N, Mangani C, Wu M, Zhang R, Kimura T, Terashima K, Bizen N, Kimura R, Wang W, Murota Y, Kokubu Y, Nobuhisa I, Kagawa T, Kitabayashi I, Bradley M, Taga T.
  • Journal Title: Stem Cells Volume: 34 Issue: 5 Pages: 1151-1162
  • DOI: 10.1002/stem.2299
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 新規Olig2結合因子によるオリゴデンドロサイト発生機構の解析 (2018)
  • Author(s): 備前典久、矢野真人、周麗、崎村建司、竹林浩秀
  • Organizer: 第23回グリアクラブ
• [Presentation] 新規Olig2結合因子によるオリゴデンドロサイト発生機構の解明 (2018)
  • Author(s): 備前典久、矢野真人、周麗、崎村建司、竹林浩秀
  • Organizer: 第123回日本解剖学会総会全国学術集会
• [Presentation] 新規Olig2結合因子によるオリゴデンドロサイト分化機構の解析 (2017)
  • Author(s): 備前 典久、松岡 崇史、Hossain MD Ibrahim、周 麗、崎村 建司、竹林 浩秀
  • Organizer: 第122回日本解剖学会総会・全国学術集会
  • Place of Presentation: 長崎大学 医学部 (長崎県長崎市)
  • Year and Date: 2017-03-28
• [Presentation] Identification of a novel Olig2-binding factor indispensable for oligodendrogenesis in central nervous system (2017)
  • Author(s): Norihisa Bizen, Masato Yano, Li Zhou, Manabu Abe, Kenji Sakimura, Hirohide Takebayashi
  • Organizer: 2017年度次世代脳プロジェクト 冬のシンポジウム
• [Remarks] 新潟大学大学院医歯学総合研究科神経生物解剖学分野のホームページ
  • URL: http://www.med.niigata-u.ac.jp/an2/index.html