Analyses on collective cell migration of epithelial cells by controlling signal molecules with light

Research Project

Project/Area Number	18K15002
Research Category	Grant-in-Aid for Early-Career Scientists
Allocation Type	Multi-year Fund
Review Section	Basic Section 48010:Anatomy-related
Research Institution	Tokyo Medical and Dental University
Principal Investigator	INABA Hironori 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (80791334)
Project Period (FY)	2018-04-01 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000) Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords	集団遊走 / 光遺伝学 / 細胞運動 / RhoA / PI3K / 上皮 / RHOA
Outline of Final Research Achievements	Optogenetics can control signaling molecules with high spatiotemporal resolutions. In this study, we aimed to elucidate the molecular mechanisms of collective cell migration of epithelial cells, especially the mechanisms of leader cell formation and maintenance of the leader-follower relationship, using optogenetics. For this purpose, we developed a new optogenetic tool, opto-RhoAGAP. Our data suggested that activation of PI3K and proper regulation of RhoA activity are essential for the formation of leader cells. On the other hand, we could not obtain clear results about whether high RhoA activity is essential for leader-follower relationship.
Academic Significance and Societal Importance of the Research Achievements	細胞の集団遊走は器官形成、創傷治癒、癌の浸潤転移など様々な生命現象において重要な現象である。これまでの研究手法では細胞集団の中の個別の細胞の機能を操作することは困難であった。本研究では光遺伝学を用いることでこの課題の解決を目指した。光照射の時空間的な制御によって個別の細胞の機能を操作するだけではなく、シグナルの活性化について時間的な制御も可能となった。また、本研究で作製した光遺伝学ツールは他の細胞生物学研究にも応用可能である。