The role of Hippo signaling pathway in the construction of three-dimensional epithelial tissues

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460358
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Yamaguchi University (2015); Tokyo Medical and Dental University (2013-2014)
• Principal Investigator: ASAOKA Yoichi 山口大学, 医学(系)研究科(研究院), 講師 (10436644)
• Co-Investigator(Renkei-kenkyūsha): NISHINA Hiroshi 東京医科歯科大学, 難治疾患研究所, 教授 (60212122)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: Hippoシグナル伝達系 / YAP変異メダカ / 細胞張力 / 蛍光イメージング

Outline of Final Research Achievements

Previously our group reported a unique medaka mutant, hirame (hir), which means flatfish in Japanese. Due to mutation of the yes-associated protein (YAP) transcriptional co-activator, hir embryos are sensitive to deformation by gravity and exhibit a markedly flattened body. In this study, we found that actomyosin-mediated tissue tension and fibronectin fibril formation are abnormal in hir embryos, leading to tissue flattening and tissue misalignment, both of which contribute to flattened body. YAP-knockdown human 3D spheroid also exhibits collapse upon exposure to external forces, which is reminiscent of the hir phenotype. Together, these findings reveal a novel mechanism of gravitational resistance in the 3D morphogenesis of a variety of animals including fish and humans.

Free Research Field

発生生物学