Identification of the morphogenetic mechanism of adult mammalian organs with the aim of in vitro construction of three-dimensional organs

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K12678
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 90110:Biomedical engineering-related
• Research Institution: Kyushu University (2023); Institute of Physical and Chemical Research (2021-2022)
• Principal Investigator: Takeo Makoto 九州大学, 生体防御医学研究所, 准教授 (50782116)
• Co-Investigator(Kenkyū-buntansha): 辻 孝 国立研究開発法人理化学研究所, 生命機能科学研究センター, チームリーダー (50339131)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 器官再生 / 形態形成 / リズム / 毛包

Outline of Final Research Achievements

In this research, we aimed to identify the cellar and molecular mechanism of morphogenesis of tissue/organ in adult mammals. To this end, we used mouse zigzag hair shaft, which always bend 3 times, as a model system. By time course analysis of hair shaft morphology, we found that hair bend was formed according to the novel infradian rhythm with 3.5-day interval. We also found that the combination of hair matrix, a progenitor cell of hair shaft, and their micro-niche, dermal papilla, changes right before bend formation (niche switching). At this time point, Aff3 and Ptn genes are upregulated and suppression of forced activation of these genes result in the disturbance of the timing of niche switching and bend formation. In addition, the disturbance of the bend formation was observed aged mice. These results show the cellar and molecular mechanism of tissue morphogenesis in adult mammals.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

本研究により、哺乳類成体における組織の形態形成メカニズムの一端が明らかになるとともに、老化個体では、この形態形成パターンが乱れることが明らかになった。これらの結果は、単に出生後の組織・器官形態がどのように維持されているかという発生学的問題を明らかにしただけではなく、幹細胞分野においてもニッチと前駆細胞の組み合わせが周期的に変化するという新たな視点をもたらした。また、老化現象が、生体リズムの乱れに起因する形態形成パターンの秩序性低下と考えられることから、本研究成果は加齢医学研究へも貢献できるものと期待される。