2019 Fiscal Year Final Research Report

3D morphogenesis of epithelial cell sheets in vitro

Planned Research

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Project Area	Discovery of the logic that establishes the 3D structure of organisms
Project/Area Number	15H05858
Research Category	Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
Allocation Type	Single-year Grants
Review Section	Biological Sciences
Research Institution	Hokkaido University
Principal Investigator	Haga Hisashi 北海道大学, 先端生命科学研究院, 教授 (00292045)
Co-Investigator(Kenkyū-buntansha)	石原誠一郎北海道大学, 先端生命科学研究院, 助教 (10719933) 古澤和也北海道大学, 先端生命科学研究院, 助教 (00510017)
Project Period (FY)	2015-06-29 – 2020-03-31
Keywords	細胞・組織 / 上皮細胞シート / ゲル基質 / アクトミオシン / 集団運動
Outline of Final Research Achievements	Three-dimensional morphogenesis of epithelial cells plays pivotal roles in many biological events as it is observed in embryogenesis. Mechanical properties of the extracellular substrate such as viscoelasticity and geometrical constraints are known as crucial factors that affect 3D morphogenesis of epithelial sheets. In this study, we found that epithelial cells (MDCK cells) cultured on a Matrigel crosslinked by Genipin exhibit dome formation by both the swelling of extracellular matrix and aquaporin water transport triggered by the basal hypertonic stress. Computer simulation was conducted and revealed that uneven swelling with a positive feedback between extending cell and enhanced water transport induces the dome formation. Moreover, we succeeded to establish a novel spherical substrate for cell culture by using a gelatin gel capsule. Human dermal fibroblasts cultured on the gel capsule made wrinkle-like structures on the spherical substrate, mimicking the early embryogenesis.
Free Research Field	細胞生物学
Academic Significance and Societal Importance of the Research Achievements	インビトロでの実験は，原理の発見には有効であるが，観察した現象がアーティファクトである可能性がある．本研究では，消化管形成，体節形成などを観察するインビボの計画班と協調し，インビトロとインビボの現象を対比しながら研究を進めることができた．また，３Ｄ形態が形成されるロジックを理解するためには，数理モデルが不可欠である．本研究では，３Ｄシミュレーションを担当する計画班と連携することで，細胞集団の回転やドーム形成の力学モデルを構築することができた．このように，インビボ，インビトロ，数理の連携によって，一見複雑に見えるインビボでの現象をシンプルな数理モデルで解明する新たなスキームが構築された．