Visualization of ECM dynamics

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K22631
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 53:Organ-based internal medicine and related fields
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Hironobu Fujiwara 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 (20615744)
• Project Period (FY): 2019-06-28 – 2022-03-31
• Keywords: 細胞外マトリックス / 基底膜 / ダイナミクス / ライブイメージング / 皮膚発生

Outline of Final Research Achievements

In recent years, the importance of the physical properties of the ECM (e.g. dynamics and elasticity) has been demonstrated, but the actual dynamics and its importance in mammalian tissues is unknown, as no effective basement membrane live imaging tools have been developed. In this research project, we generated knock-in mice that can visualise basement membrane dynamics, and establish a system that enables 4D imaging of basement membrane dynamics. Furthermore, by combining FRAP method, we established quantitative methods for examining basement membrane movement, elongation and turnover in live tissues. In addition, perturbation of basement membrane dynamics with drugs caused abnormalities in the cell fate and tissue morphology of the skin epithelium. In the future, this system will be used to reveal the involvement of basement membrane dynamics in skin development, homeostasis and diseases.

Free Research Field

皮膚科学

Academic Significance and Societal Importance of the Research Achievements

基底膜遺伝子の異常は、皮膚を含む多くの臓器の先天性疾患や疾病の原因となるが、基底膜が働くメカニズムの理解は不十分である。本研究では、基底膜が「動く」「伸びる」「曲がる」といったダイナミックな特性の変化を細胞挙動とともに可視化できるマウスとイメージングシステムを確立した。これを用いることで、皮膚の発生、創傷治癒、がんの浸潤転移などの際の基底膜ダイナミクスとその役割の理解が飛躍的に進むと期待される。