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Mechanisms of tension homeostasis and its role in epithelial morphogenesis

Research Project

Project/Area Number 16K18544
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Cell biology
Research InstitutionNational Institute for Physiological Sciences

Principal Investigator

Otani Tetsuhisa  生理学研究所, 生体機能調節研究領域, 助教 (50415105)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords密着結合 / 上皮細胞 / 上皮バリア / 上皮極性 / ZO-1 / 上皮管腔構造 / 張力 / 接着結合 / アクチン / ミオシン
Outline of Final Research Achievements

Tight Junctions are essential for epithelial barrier formation. In addition to its roles in epithelial barrier, Tight Junctions are thought to regulate epithelial polarity and actomyosin organization, although the detailed molecular mechanisms remained unclear. We have generated ZO-1/ZO-2 double KO cells by genome editing. In ZO-1/ZO-2 double KO cells, Tight Junctions were not formed and epithelial barrier was disrupted. In addition, abnormal accumulation of myosin was observed. Unexpectedly, we found that epithelial polarity was disorganized in ZO-1/ZO-2 deficient cells. Furthermore, ZO-1/ZO-2 deficient cells failed to form polarized cysts when cultured in collagen gel. In contrast, when Adherens Junctions were perturbed, epithelial barrier formation and myosin assembly was not impaired, and epithelial polarity was well developed. These results suggest that ZO-1 and ZO-2 regulate epithelial polarization through Tight Junctions assembly.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (7 results)

All 2017 2016

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (6 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] IKKε inhibits PKC to promote Fascin-dependent actin 2016bundling2016

    • Author(s)
      Otani T, Ogura Y, Misaki K, Maeda T, Kimpara A, Yonemura S, Hayashi S
    • Journal Title

      Development

      Volume: 143 Issue: 20 Pages: 3806-3816

    • DOI

      10.1242/dev.138495

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Epithelial barrier homeostasis by cell competition.2017

    • Author(s)
      Tetsuhisa Otani, Mikio Furuse
    • Organizer
      The 3rd International Symposium on Cell Competition, Cell Competition and Cancer,
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 上皮バリアの恒常性の維持における細胞競合の役割2017

    • Author(s)
      大谷哲久、古瀬幹夫
    • Organizer
      第50回日本発生生物学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 上皮極性における密着結合の役割2017

    • Author(s)
      大谷哲久、徳田深作、古瀬幹夫
    • Organizer
      第69回日本細胞生物学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 上皮バリアのホメオスタシスにおける細胞競合の役割2017

    • Author(s)
      大谷哲久、古瀬幹夫
    • Organizer
      第7回名古屋大学医学系研究科・生理学研究所 合同シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] ZO-1 and ZO-2 are required for epithelial polarity in MDCK II cells2016

    • Author(s)
      Tetsuhisa Otani
    • Organizer
      International Conference Tight junctions and their proteins
    • Place of Presentation
      ドイツ・ベルリン
    • Year and Date
      2016-09-08
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 上皮極性における密着結合の役割2016

    • Author(s)
      大谷哲久、徳田深作、渡邊美香、古瀬幹夫
    • Organizer
      第68回日本細胞生物学会大会
    • Place of Presentation
      京都テルサ(京都府京都市)
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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