Elucidation of the mechanical mechanism by which cell chirality induces left-right asymmetric gut tube twisting

• Project/Area Number: 18K06255
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 44020:Developmental biology-related
• Research Institution: Osaka University
• Principal Investigator: Inaki Mikiko 大阪大学, 理学研究科, 講師 (10747679)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 細胞キラリティ / 左右非対称性 / 器官形成 / アクチン細胞骨格 / 細胞スライド / 細胞移動

Outline of Final Research Achievements

Many organisms show left-right asymmetrical morphology and functions in their external and internal structures and the formation of left-right asymmetry is essential for the normal development. The applicant has been studying the mechanism by which cell chirality (cellular left-right asymmetry) induces the left-right asymmetric morphology of internal organs in vivo using the Drosophila embryonic hindgut as a model system. We have shown that cell chirality causes left-right asymmetrical gut tube twisting through a novel cellular behavior "chiral cell sliding". In this study, RNA interference screening, ex vivo tissue culture, and ultra-resolution live imaging showed the mechanisms that induce cell chirality and sliding.

Academic Significance and Societal Importance of the Research Achievements

細胞キラリティは、近年、様々な脊椎動物由来の培養細胞でも発見され、キラルな動態へのアクチン細胞骨格系の関与が示唆されている。しかし、本研究で明らかにしようとしている、細胞キラリティの形成機構やそれにより誘導される組織変形の機構については、ほとんどわかっていない。本研究において、細胞キラリティが形成され、組織変形を誘導する機構を明らかにすることで、この分野の発展を世界的にリードできる。本研究により、新たな組織変形の機構が明らかになり、臓器の再生などへの応用が期待できる。

Research Products

• [Journal Article] Statistical Validation Verifies That Enantiomorphic States of Chiral Cells Are Determinant Dictating the Left- or Right-Handed Direction of the Hindgut Rotation in Drosophila (2020)
  • Author(s): Ishibashi Tomoki、Inaki Mikiko、Matsuno Kenji
  • Journal Title: Symmetry Volume: 12 Issue: 12 Pages: 1991-1991
  • DOI: 10.3390/sym12121991
  • Peer Reviewed / Open Access
• [Journal Article] Cells with broken left-right symmetry: roles of intrinsic cell chirality in left-right asymmetric epithelial morphogenesis. (2019)
  • Author(s): Utsunomiya, S., Sakamura, S., Sasamura, T., Ishibashi, T., Maeda, C., Inaki, M., and Matsuno K.
  • Journal Title: Symmetry Volume: 11 (4) Issue: 4 Pages: 505-505
  • DOI: 10.3390/sym11040505
  • Peer Reviewed / Open Access
• [Journal Article] Chiral cell sliding drives left-right asymmetric organ twisting (2018)
  • Author(s): Mikiko Inaki, R.Hatori, N.Nakazawa, T.Okumura, T.Ishibashi, J.Kikuta, M.Ishii, K.Matsuno, H.Honda
  • Journal Title: eLife Volume: 7
  • DOI: 10.7554/elife.32506
  • NAID: 120006491604
  • Peer Reviewed / Open Access
• [Journal Article] Cell Chirality Drives Left-Right Asymmetric Morphogenesis (2018)
  • Author(s): Inaki Mikiko、Sasamura Takeshi、Matsuno Kenji
  • Journal Title: Frontiers in Cell and Developmental Biology Volume: 6 Pages: 1-9
  • DOI: 10.3389/fcell.2018.00034
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] A novel 3D morphologic change of the cell, chiral cell twisting, may drive left-right directional tissue rotation (2020)
  • Author(s): Inaki M, Yukumatsu M, Takigawa T, Okubo A, Sushida T, Akiyama M, Inoue Y, Matsuno K
  • Organizer: 第43回 分子生物学会年会
• [Presentation] 3次元シミュレーションにより明らかとなった細胞のキラルなねじれによるショウジョウバエの消化管捻転の機構 (2020)
  • Author(s): 稲木 美紀子、行松 美樹、瀧川 大志、須志田 隆道、秋山 正和、井上 康博、松野 健治
  • Organizer: 第72回 細胞生物学会大会
• [Presentation] Three-dimensional simulation of epithelial tube revealed a chiral cellular behavior, cell twisting that may account for the directional gut rotation in Drosophila (2020)
  • Author(s): Mikiko Inaki, Miki Yukumatsu, Taishi Takigawa, Takamichi, Sushida, Masakazu Akiyama, Yasuhiro Inoue, Kenji Matsuno
  • Organizer: 第53回 発生生物学会大会
• [Presentation] Three-dimensional simulation of epithelial tube revealed distinctive chiral cellular behaviors that may account for the directional tissue rotation (2019)
  • Author(s): Mikiko Inaki, Taishi Takigawa, Akino Okubo, Takamichi Sushida, Masakazu Akiyama, Yasuhiro Inoue, Kenji Matsuno
  • Organizer: 第42回 分子生物学会年会
• [Presentation] Chiral cell sliding drives left-right asymmetric organ rotation (2019)
  • Author(s): Inaki M, Honda H, Matsuno K
  • Organizer: EDBC Alicante 2019
  • Int'l Joint Research
• [Presentation] 消化管の左右非対称な捻転を引き起こす上皮細胞の3次元形態変化 (2019)
  • Author(s): 稲木美紀子、瀧川大志、大久保明野、須志田隆道、秋山正和、井上康博、松野健治
  • Organizer: 第19回日本タンパク質科学会年会、第71回日本細胞生物学会大会合同年次大会
• [Presentation] A novel 3D morphologic change, cell twisting, may drive left-right directional tissue rotation. (2019)
  • Author(s): Inaki M, Takigawa T, Okubo A, Sushida T, Akiyama M, Inoue Y, Matsuno K
  • Organizer: 52nd Annual meeting of the JSDB
  • Invited
• [Presentation] Chiral cell sliding drives left-right asymmetric organ twisting. (2018)
  • Author(s): Inaki M, Honda H, Matsuno K
  • Organizer: 8th World Congress of Biomechanics
  • Int'l Joint Research
• [Presentation] A novel 3D morphologic change of epithelial cells, cell twisting, may account for left-right directional tissue rotation. (2018)
  • Author(s): Inaki M, Okubo A, Sushida T, Akiyama M, Inoue Y, Matsuno K
  • Organizer: 第69回 日本細胞生物学会、第51回 日本発生生物学会合同大会
• [Presentation] キラルな細胞変形によって駆動される組織自律的な内臓捻転の機構 (2018)
  • Author(s): 稲木美紀子、大久保明野、須志田隆道、秋山正和、井上康博、松野健治
  • Organizer: 第41回 分子生物学会年会
  • Invited