Elucidation of response characteristics in cellular mechano-sensing system for maintaining tube diameter

2019 Fiscal Year Final Research Report

• Project/Area Number: 17KT0107
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 特設分野
• Research Field: Constructive Systems Biology
• Research Institution: Kyoto University
• Principal Investigator: Hirashima Tsuyoshi 京都大学, 医学研究科, 講師 (10620198)
• Project Period (FY): 2017-07-18 – 2020-03-31
• Keywords: 上皮管 / ERK / メカノバイオロジー / 数理モデル / ライブイメージング / 精巣上体 / 肺 / 内耳

Outline of Final Research Achievements

To elucidate the mechanisms of mechano-response (force reception and response) for the regulation of the morphology in multicellular tissues, we studied the developmental processes of various fetal murine organs using imaging techniques and mathematical models. Using the epididymis, we have revealed the mechanism by which the diameter of the epithelial tube is maintained by the active rearrangement of surrounding cells in response to cell division along the circumferential direction of the epithelial tube. We also focused on the force-responsive MAP kinase/ERK, and performed FRET (fluorescence resonance energy transfer) imaging measurements to evaluate ERK activity, revealing a mechanism by which dynamic behaviors of ERK-activated cells contribute to morphogenesis during lung and inner ear development.

Free Research Field

発生生物学/生物物理学

Academic Significance and Societal Importance of the Research Achievements

細胞特有の「力を受容し力生成で応答する」メカノレスポンスと組織の形態形成を結びつけた本研究内容は、生物の自発的なかたち作りを理解する上で重要な成果である。また、上皮管腔構造は内臓に普遍的に見られる構造であり、その大きさやかたちの制御機構の解明の一端を担う本研究成果は、正常発生や病態疾患の理解につながる。たとえば、再生医療分野で注目されるオルガノイドの形態の品質管理に貢献することが期待される。