Robust, time-dependent coordination of tissue growth through cell-cell communications

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22423
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 44:Biology at cellular to organismal levels, and related fields
• Research Institution: Nagoya University
• Principal Investigator: Ohsawa Shizue 名古屋大学, 理学研究科, 教授 (80515065)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Keywords: 組織成長 / 細胞間相互作用 / 成長遅延 / ショウジョウバエ

Outline of Final Research Achievements

Highly reproducible tissue development is achieved by robust, time-dependent coordination of cell proliferation and cell death. To study the mechanisms underlying robust tissue growth, we analyzed the developmental process of larval Drosophila Minute mutants, a series of mutants for a ribosomal protein gene, which show significantly prolonged larval period but develop into normal flies. Surprisingly, we found that both cell death and compensatory cell proliferation were dramatically increased in developing wing discs of Minute animals. Blocking the cell-turnover resulted in various morphological defects, indicating the essential role of cell-turnover in Minute wing morphogenesis. Genetic analyses showed that Minute wing discs elevate Wg expression, which cooperates with developmental delay for the induction of cell-turnover. Our findings suggest a novel paradigm for robust coordination of tissue growth by cell-turnover, which is induced when developmental time axis is distorted.

Free Research Field

発生遺伝学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、「細胞集団挙動を介した発生時間軸制御」という、多細胞コミュニティが内包する新しい動的恒常性維持機構の存在を示唆するものであり、発生生物学や、表現型制約の仕組みを解析する進化生物学の発展に大きく貢献し得ると期待される。また興味深いことに、今回モデルとして用いたMinute変異体と同様のリボソームタンパク質遺伝子のヘテロ変異が様々なヒトの疾患（リボソーム病と総称される）を引き起こすことが知られている。今後、分子基盤を明らかにすることで、いまだ大きな謎であるリボソーム病の発症機序の解明とその新たな治療戦略の基盤構築に将来的にはつながり得ると考えられる。