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アピカル面競合による上皮細胞の選別機構

Publicly Offered Research

Project AreaCell competition: a mechanism for survival of the fittest in the multi-cellular community
Project/Area Number 15H01501
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

林 茂生  国立研究開発法人理化学研究所, 多細胞システム形成研究センター, チームリーダー (60183092)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥12,220,000 (Direct Cost: ¥9,400,000、Indirect Cost: ¥2,820,000)
Fiscal Year 2016: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2015: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Keywords細胞競合 / Fitness / ショウジョウバエ / 細胞脱離 / 頂端面 / 極性分子 / 上皮 / 胚発生 / ライブイメージング / 上皮細胞 / 細胞の脱離 / 細胞の挿入 / 細胞極性
Outline of Annual Research Achievements

細胞競合は等価な細胞集団において特定の細胞が増殖と生存の優位性(Fitness)を獲得し、fitnessの劣る細胞は組織から排除されるとする考え方である.細胞競合は遺伝的に標識された二種類の細胞集団の増殖率を比較する事で検出されるため、増殖と成長が緩やかな組織で細胞競合が起こるのかについての知見はまだない。本研究では細胞増殖を伴わない細胞競合が起きるかを検討した。ショウジョウバエ胚発生後期(細胞分裂15-16回目)では外胚葉に細胞が密集し表面張力がプラス(押し合い)の状態で頂端面の拡大縮小を繰り返すゆらぎの状態にあり、体節間の溝や各種器官の原基を内部に陥入させる原動力となっている。ライブイメージングにより外胚葉の細胞が一定の頻度で個別に頂端面積を減少させ、その一部の細胞が基部側に脱離することを見いだした。この脱離運動の容態に関して以下の知見を得た。1)細胞脱離はミオシン集積や核の凝集を伴わず、細胞死による脱離とは様相が異なる。2)神経分化においても脱離が起こる事が知られているがstage11の細胞脱離は神経細胞の大幅な減少を招くAc/Sc遺伝子の欠損変異体においても見られる。3)頂端面はsubapical(SA)とその基部側に位置する接着結合部位(AJ)に分かれるが脱離に際してはAJマーカー(Par6, p120CTN)が維持されるのに対しSA分子(Crumbs, aPKC)は減少することを見いだした。4)Crumbsの遺伝子量を1/2にした個体では細胞脱離の頻度が上昇する。これらの結果から頂端面のSA分子量はゆらぎ状態にあり、それらが閾値を下回ると頂端面を維持できず脱離すると考えられた。これらの結果はSA面の極性分子がFitnessの指標となり、その消失が脱離というかたちで細胞排除につながると解釈出来る。

Research Progress Status

28年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

28年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (17 results)

All 2017 2016 2015

All Journal Article (7 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 7 results,  Open Access: 7 results,  Acknowledgement Compliant: 7 results) Presentation (10 results) (of which Int'l Joint Research: 5 results,  Invited: 4 results)

  • [Journal Article] Microtubule-dependent balanced cell contraction and luminal-matrix modification accelerate epithelial tube fusion.2016

    • Author(s)
      Kato, K., Dong, B., Wada, H., Tanaka-Matakatsu, M., Yagi, Y., Hayashi, S.
    • Journal Title

      Nature Communications

      Volume: 7 Issue: 1 Pages: 000-000

    • DOI

      10.1038/ncomms11141

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [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 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Escargot controls the sequential specification of two tracheal tip cell types by suppressing FGF signaling in Drosophila2016

    • Author(s)
      Miao G, Hayashi S
    • Journal Title

      Development

      Volume: 143 Issue: 22 Pages: 4261-4271

    • DOI

      10.1242/dev.133322

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] A cortical instability drives periodic supracellular actin pattern formation in epithelial tubes.2015

    • Author(s)
      Hanezzo E., Dong B., Recho P., Joanny J-F., Hayashi S.
    • Journal Title

      Proc. Natl. Acad. Sci. U.S.A.

      Volume: 112 Issue: 28 Pages: 8211-8625

    • DOI

      10.1073/pnas.1504762112

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Transport and retention mechanism for the sustained distal localization of Spn-F/ IKKε during Drosophila bristle elongation.2015

    • Author(s)
      Otani T., Oshima K., Kimpara A., Takeda M., Abdu U., Hayashi S.
    • Journal Title

      Development

      Volume: 142 Pages: 2338-2351

    • DOI

      10.1242/dev.121863

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Shaping of biological tubes by mechanical interaction of cell and extracellular matrix.2015

    • Author(s)
      Dong B., Hayashi S.
    • Journal Title

      Current Opinion in Genetics & Development

      Volume: 32 Pages: 129-134

    • DOI

      10.1016/j.gde.2015.02.009

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Mechanisms of cell height changes that mediate epithelial invagination.2015

    • Author(s)
      Kondo T., Hayashi S.
    • Journal Title

      Develp. Growth and Diff.

      Volume: 57 Issue: 4 Pages: 313-323

    • DOI

      10.1111/dgd.12224

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Invagination in polar coordinate system: role of radially propagating EGFR-ERK signaling for the tracheal invagination in Drosophila2017

    • Author(s)
      林 茂生
    • Organizer
      4D細胞計測全体会議
    • Place of Presentation
      理化学研究所、和光市、埼玉県
    • Related Report
      2016 Annual Research Report
  • [Presentation] イントロダクション:生命機能の基盤となる細胞形態の多様性とゆらぎ2016

    • Author(s)
      林 茂生
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜、横浜市、神奈川県
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] Escargot controls the sequential specification of two tracheal tip cells by suppressing FGF signaling in Drosophila2016

    • Author(s)
      林 茂生
    • Organizer
      日本発生生物学会秋季シンポジウム2016
    • Place of Presentation
      三島市民文化会館、三島市、静岡県
    • Year and Date
      2016-10-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] アピカル面競合による上皮細胞の選別機構2016

    • Author(s)
      林 茂生
    • Organizer
      第4回新学術領域「細胞競合」班会議
    • Place of Presentation
      東京大学薬学講堂、文京区、東京都
    • Year and Date
      2016-08-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] Cell specification and cell geometry change during tracheal branch fusion2016

    • Author(s)
      林 茂生
    • Organizer
      2016 EMBO CONFERENCE The Molecular & Developmental Biology of Drosophila
    • Place of Presentation
      ハニア、ギリシア
    • Year and Date
      2016-06-19
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Microtubule-dependent balanced cell contraction accelerates epithelial tube fusion2016

    • Author(s)
      林 茂生
    • Organizer
      第68回日本細胞生物学会・第11回日本ケミカルバイオロジー学会 合同大会
    • Place of Presentation
      京都テルサ、京都市、京都府
    • Year and Date
      2016-06-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] Genetic and physical mechanisms behind tube geometry and size control2016

    • Author(s)
      林 茂生
    • Organizer
      CDB Symposium 2016 “Size in Development: Growth, Shape and Allometry”
    • Place of Presentation
      理化学研究所、兵庫県、神戸市
    • Year and Date
      2016-03-28
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Transport and retention mechanism for the sustained distal organizer localization during Drosophila bristle elongateion2015

    • Author(s)
      林 茂生
    • Organizer
      Asian-Pacific Developmental Biology Conference,
    • Place of Presentation
      Xian China
    • Year and Date
      2015-09-12
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Cell extrusion from epithelia undergoing morphogenetic movement2015

    • Author(s)
      林 茂生
    • Organizer
      1st International Symposium on Cell Competition, “Cell Competition in Development and Cancer”、京都大学
    • Place of Presentation
      芝蘭会館、京都府、京都市
    • Year and Date
      2015-09-10
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Role of apical extracellular matrix in epithelial tube morphogenesis2015

    • Author(s)
      林 茂生
    • Organizer
      Asian-Pacific Drosophila Conference,
    • Place of Presentation
      Beijin, China
    • Year and Date
      2015-05-13
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited

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Published: 2015-04-16   Modified: 2018-03-28  

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