Investigation of the molecular mechanisms regulating adult vertebrate brain regeneration using comparative biological approaches

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15195
• 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
• 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): 2021-04-01 – 2024-03-31
• Keywords: 神経新生 / 血管新生 / 瘢痕形成 / 比較トランスクリプトーム

Outline of Final Research Achievements

Comparing the transcriptome between zebrafish and medaka with differential regenerative capacity, we attempted to elucidate the molecular mechanisms that regulate the high regenerative ability of zebrafish and to investigate the factors that promote regeneration. Pathway analysis revealed that the immune response and Jak-Stat pathway are activated earlier and converge earlier in zebrafish. In the search for regenerative factors, 12 secreted factors were extracted, and 5 of them were previously reported to have a promoting effect, suggesting that a comparative analysis approach would be useful. Analysis using human neural stem cells revealed that two of the six factors able to promote proliferation of neural stem cells.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

ゼブラフィッシュ-メダカを用いた比較系が中枢神経系の再生制御機構の解明や再生促進因子の探索に有用であることが示された。さらには、再生能力が低いメダカ個体やマウス個体、ヒト神経幹細胞の培養系を用いて、抽出された解析候補因子の機能解明を進めることで効率的に神経を促す因子の同定や哺乳類への応用が期待される。メダカは乏しい神経再生能や血管再生能を有し、損傷により瘢痕が形成されるなど哺乳類に近い損傷応答を示す唯一の報告がある小型魚類モデルある。再生能力が高いゼブラフィッシュと同じ損傷モデルが作成可能であり、網膜や脊髄の損傷モデルの比較解析などを通じて、神経再生を制御する分子機構の更なる解明が期待される。