Elucidation of the roles of the Hippo-YAP signaling pathway in regulating cell tension in liver development and regeneration

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03381
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Nishina Hiroshi 東京医科歯科大学, 難治疾患研究所, 教授 (60212122)
• Co-Investigator(Kenkyū-buntansha): 小藤 智史 東京医科歯科大学, 難治疾患研究所, 講師 (00508153)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 肝臓 / 細胞排除 / 細胞間張力 / YAP

Outline of Final Research Achievements

The liver forms three-dimensional (3D) structures of a certain size through cell proliferation and cell differentiation. We have isolated a medaka mutant in which tissues including epithelium become flattened, and analysis of this mutant revealed that the transcriptional co-activator YAP plays an essential role in 3D organogenesis via cell tension. We also found that overexpression of YAP in canine renal epithelial cells MDCK induced pressure in neighboring cells and pushed YAP-expressing cells to the apical surface. Therefore, we attempted to visualize the physical forces by utilizing a FRET probe (mCherry-spider silk protein-EGFP containing the basic structure). We found that FRET was induced between two MDCK cells in a time-dependent manner. Thus these results indicate the existence of the pressure generated between two cells to be eliminated.

Free Research Field

分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

転写共役因子YAPは様々ながんの発症や悪性化に関与することが指摘されているが、その分子機構については不明な点が多い。実際、ヒト癌においてYAP遺伝子変異の報告は多くなく、どのように病態に関与しているかは国内外を通じて課題となっている。本研究成果から、この理由の一つとして、これまでの細胞生物学では検出が困難であった細胞間張力の制御が考えられる。すなわち、YAP依存性の細胞間張力制御機構の解明は発がん機構の解明の一端を解明に貢献すると期待される。