Principle of body malfunctioning through local cell division failure

2023 Fiscal Year Final Research Report

• Project/Area Number: 19KK0181
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 44:Biology at cellular to organismal levels, and related fields
• Research Institution: Hokkaido University
• Principal Investigator: Uehara Ryota 北海道大学, 先端生命科学研究院, 准教授 (20580020)
• Co-Investigator(Kenkyū-buntansha): 塚田 祐基 慶應義塾大学, 理工学部(矢上), 講師 (80580000) ; 松尾 和哉 京都工芸繊維大学, 分子化学系, 助教 (90764952)
• Project Period (FY): 2019-10-07 – 2024-03-31
• Keywords: 細胞分裂 / ゼブラフィッシュ / 光制御

Outline of Final Research Achievements

Cell division failure causes a wide range of diseases, but the quantitative relationship between the magnitude of cell division defects and their effects on the body function is unknown. In this study, we newly developed a light-responsive mitotic inhibitor. By light control using this compound, various levels of cell division defects were induced with various temporal patterns in early zebrafish embryos. We found embryos were highly resistant to one or two rounds of whole-body cell division failures during 2-4 hours post-fertilization (hpf) and to more severe mitotic failures after 5 hpf with almost intact tissue formation. Especially in the latter case, we found that the spindle checkpoint plays an important role in reducing the lethality of mitotic abnormalities.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本成果から、生体が甚大な分裂制御不全を経て形成された異常細胞を保持したままその機能を維持し得ることが定量的に明らかになった。疾病制御の観点からは、このような生体の許容性ががん発症などの長期的リスクを高めることが推察される。環境保全の観点では、甚大な分裂障害によるゲノム異常が長期間生体に滞留する可能性が示唆され、これが次世代へどの程度継承され生態系に作用をもちうるかの検証が必要と考えられる。