Analysis of Molecular Mechanisms Regulating the Regenerative Capacity of the Adult Vertebrate Brain

• Project/Area Number: 18K14824
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 46010:Neuroscience-general-related
• Research Institution: National Institute of Advanced Industrial Science and Technology (2019-2021); Waseda University (2018)
• Principal Investigator: Shimizu Yuki 国立研究開発法人産業技術総合研究所, 生命工学領域, 研究員 (30778064)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 神経再生 / ゼブラフィッシュ / ラジアルグリア / 遺伝子発現変動解析 / 組織再生 / 中枢神経系

Outline of Final Research Achievements

In this research project, we compared gene expression after injury in mice and zebrafish because of their different regenerative abilities in the central nervous system, in order to elucidate the molecular mechanisms that contribute to the high regenerative ability of the zebrafish. Comprehensive comparison of gene expression after brain injury identified secreted factors that are increased only in zebrafish and confirmed that one of secreted factors regulates neural stem cell proliferation in human neural stem cells and zebrafish brain injury models.

Academic Significance and Societal Importance of the Research Achievements

本研究課題は再生能の異なる生物種間の比較解析により、神経再生促進因子の同定を目指したものであるが、ゼブラフィッシュとマウスの比較解析により既知の再生促進因子の抽出に成功し、さらに神経幹細胞の増殖を促す新規因子を同定した。本研究による成果は、比較生物学的なアプローチが再生を制御する分子機構の解明および再生促進因子の同定に効果的であるということを示唆していると考える。神経再生を促すためには、神経新生、血管新生、抗炎症など多岐にわたる作用を有する因子が効果的であると考えられており、小型魚類-マウス間比較による探索の拡充および哺乳類での機能評価系を確立し、有望な因子の同定を目指す。

Research Products

• [Journal Article] Transcriptome Analyses Reveal IL6/Stat3 Signaling Involvement in Radial Glia Proliferation After Stab Wound Injury in the Adult Zebrafish Optic Tectum (2021)
  • Author(s): Shimizu Yuki、Kiyooka Mariko、Ohshima Toshio
  • Journal Title: Frontiers in Cell and Developmental Biology Volume: 9 Pages: 668408-668408
  • DOI: 10.3389/fcell.2021.668408
  • Peer Reviewed / Open Access
• [Journal Article] Histone deacetylase inhibition promotes regenerative neurogenesis after stab wound injury in the adult zebrafish optic tectum (2020)
  • Author(s): Kiyooka Mariko、Shimizu Yuki、Ohshima Toshio
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 529 Issue: 2 Pages: 366-371
  • DOI: 10.1016/j.bbrc.2020.06.025
  • Peer Reviewed
• [Journal Article] Involvement of sonic hedgehog and notch signaling in regenerative neurogenesis in adult zebrafish optic tectum after stab injury (2018)
  • Author(s): Ueda Y, Shimizu Y, Shimizu N, Ishitani T, Ohshima T.
  • Journal Title: Journal of Comparative Neurology Volume: 526 Issue: 15 Pages: 2360-2372
  • DOI: 10.1002/cne.24489
  • Peer Reviewed
• [Presentation] Comparative analysis of brain injury models using small fish with different regenerative abilities (2020)
  • Author(s): 清水勇気
  • Organizer: 第43回日本分子生物学会年会
• [Presentation] 小型魚類を用いた脳損傷モデルの作製および 組織再生を制御する分子機構の探索 (2019)
  • Author(s): 清水勇気
  • Organizer: 第5回 ゼブラフィッシュ・メダカ創薬研究会(ZMDD2019)
• [Presentation] Analysis of molecular mechanisms regulating proliferation of radial glia after stab injury in adult optic tectum. (2019)
  • Author(s): Shimziu Y, Kiyooka M and Ohshima T
  • Organizer: The 14th international zebrafish conference
  • Int'l Joint Research
• [Presentation] Analysis of Shh signaling on radial glia proliferation and differentiation after stab injury in the adult zebrafish optic tectum (2018)
  • Author(s): Shimizu Y, Ueda Y, Ohshima T.
  • Organizer: 11th Zebrafish Disease Models Conference
  • Int'l Joint Research