Conprehemsive understanding of tissue regeneration processes frombreak down of homeostasis to morphological regeneration

2023 Fiscal Year Final Research Report

• Project/Area Number: 19H03232
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 44020:Developmental biology-related
• Research Institution: Tokyo Institute of Technology
• Principal Investigator: Kawakami Atsushi 東京工業大学, 生命理工学院, 准教授 (00221896)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 組織再生 / ゼブラフィッシュ / ヒレ / 幹細胞 / トランスジェニック

Outline of Final Research Achievements

Multicellular organisms have an ability to maintain and regenerate their body parts over long periods of time, but many aspects of this mechanism remain unknown. In this study, using the zebrafish caudal fin model, we performed an analysis focusing on the important steps of tissue regeneration processes, and obtained the following results. (1) PI3 kinase signaling is required for macrophage recruitment in the injury response. (2) For transcriptional response of genes, signals via two transcription factor binding sites are simultaneously activated. (3) Mesenchymal cells, which produce and regenerate bone and cartilage, take different lineages during development and maintain throughout life. (4) Self-renewal of skin basal stem cells and keratinocyte differentiation are induced by injury to basal cells and keratinocytes, respectively. The above results greatly contributed to the understanding of the regeneration process.

Free Research Field

再生生物学

Academic Significance and Societal Importance of the Research Achievements

イモリや魚類などは，失った四肢や鰭を完全に再生することができる。この驚くべき能力の解明は近年急速に進んできたが，依然として，再生を哺乳類において人為的に制御できるには遠い。本研究では，再生の開始におけるマクロファージの動員機構，遺伝子の再生応答，さらに，組織の主要な部分を作る間葉（骨細胞と軟骨細胞）と皮膚細胞の由来・多様性・分化多能性を明らかにし，再生プロセスの重要なステップに関する知見を大きく前進させた。
このような再生過程の解明から、ほ乳類で再生能力が限定されている原因や、いかにして組織が一定に保たれているか、さらに幹細胞から組織，器官を作る技術へと繋がることが期待される。