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Deciphering of left-right asymmetry -Identification of new molecules during L-R determination and proof of

Research Project

Project/Area Number 16H02618
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field General physiology
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

MOCHIZUKI NAOKI  国立研究開発法人国立循環器病研究センター, 研究所, 研究所長 (30311426)

Research Collaborator Fukui Hajime  国立循環器病研究センター, 研究所細胞生物学部所属
Ando Koji  国立循環器病研究センター, 研究所細胞生物学部所属
Miyazaki Takahiro  国立循環器病研究センター, 研究所細胞生物学部所属
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥44,590,000 (Direct Cost: ¥34,300,000、Indirect Cost: ¥10,290,000)
Fiscal Year 2018: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
Fiscal Year 2017: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
Fiscal Year 2016: ¥22,490,000 (Direct Cost: ¥17,300,000、Indirect Cost: ¥5,190,000)
Keywords左右差 / クッパ―胞 / Hippo シグナル / ゼブラフィッシュ / 繊毛 / 発生 / Hippo / カルシウム / 非対称 / Yap1 / Wwtr1 / 左右非対称 / 心臓前駆細胞 / 心臓形成 / Hippoシグナル / Kupffer's vesicle / sox17 / Arl13b
Outline of Final Research Achievements

Left-right asymmetry is essential for body planning as well as anterior-posterior and dorsal-ventral axes. We focused on the mechanism by which kupffer's vescile (KV) and cilia in the KV are organized during zebrafish embryogenesis. In the classical pathway, left-right flow in the KV promoted by the rotation of cilia results in the asymmetric distribution of factors that determines the localization of progenitor cells of organs.
We developed transgenic zebrafish lines that enabled us to monitor KV cells and cilia and that enables us to visualize Ca oscillation in the KV cells. By monitoring the KV formation and cilia development, we demonstrated that Ca oscillation starts before the lumen forms inside of the KV, suggesting that Ca oscillation does not depend on the flow caused by the rotation of cilia. Furthermore, we found that Hippo signaling is dispensable for KV formation followed by cilia fomation but indispensable for correct organ distribution.

Academic Significance and Societal Importance of the Research Achievements

生命現象の根幹である体の前後、背腹、左右を決定する機構の解明は発生学、生物学の問題として重要である。この中で本研究では、左右差形成機構の解明を目的とした。クッパ―胞という発生時に一過性に生じる器官内に流れが生じて左右決定因子の不均等分布が生じることが、左右差決定の古典的なメカニズムと考えられてきた。しかし、本研究でクッパ―胞の内腔が形成される以前からカルシウムの濃度の不均一性がクッパ―胞形成細胞群に見られることがわかり、新たな左右差形成機構の存在が示唆された。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (23 results)

All 2018 2017 2016 Other

All Int'l Joint Research (2 results) Journal Article (8 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 8 results,  Open Access: 5 results,  Acknowledgement Compliant: 3 results) Presentation (10 results) (of which Int'l Joint Research: 5 results,  Invited: 5 results) Remarks (3 results)

  • [Int'l Joint Research] University of Queensland/Institute of Molecular Bioscience(オーストラリア)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] Max Planck Institute (Bad Nauheim)(ドイツ)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Hippo signaling determines the number of venous pole cells that originate from the anterior lateral plate mesoderm in zebrafish.2018

    • Author(s)
      Fukui H, Miyazaki T, Chow RW, Ishikawa H, Nakajima H, Vermot J, Mochizuki N.
    • Journal Title

      Elife

      Volume: 7 Pages: 1-24

    • DOI

      10.7554/elife.29106

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A molecular atlas of cell types and zonation in the brain vasculature2018

    • Author(s)
      Vanlandewijck M, He L,MA, Andrae J, Ando K, Del Gaudio F, Nahar K, Lebouvier T, Lavi B, Gouveia L, Sun Y, Raschperger EM, Zarb Y, Mochizuki N, Keller A, Lendahl U, Betsholtz C.
    • Journal Title

      Nature

      Volume: 554 Issue: 1 Pages: 475-480

    • DOI

      10.1038/sdata.2018.160

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A molecular atlas of cell types and zonation in the brain vasculature.2018

    • Author(s)
      Vanlandewijck M, He L, Mae MA, Andrae J, Ando K, Del Gaudio F, Nahar K, Lebouvier T, Lavin;a B, Gouveia L, Sun Y, Raschperger E, Rasanen M, Zarb Y, Mochizuki N, Keller A, Lendahl U, Betsholtz C.
    • Journal Title

      Nature

      Volume: 554 Issue: 7693 Pages: 475-480

    • DOI

      10.1038/nature25739

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cardiomyokines from the heart.2018

    • Author(s)
      Chiba A, Watanabe-Takano H, Miyazaki T, Mochizuki N.
    • Journal Title

      Cell Mol Life Sci.

      Volume: 75 Issue: 8 Pages: 1349-1362

    • DOI

      10.1007/s00018-017-2723-6

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Guidelines for morpholino use in zebrafish.2017

    • Author(s)
      Stainier DYR, Raz E, Lawson ND, Ekker SC, Burdine RD, Eisen JS, Ingham PW, Schulte-Merker S, Yelon D, Weinstein BM, Mullins MC, Wilson SW, Ramakrishnan L, Amacher SL, Neuhauss SCF, Meng A, Mochizuki N, Panula P, Moens CB.
    • Journal Title

      PLoS Genet.

      Volume: 13 Issue: 10 Pages: e1007000-e1007000

    • DOI

      10.1371/journal.pgen.1007000

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Flow-dependent endothelial YAP regulation that contributes to vessel maintenance.2017

    • Author(s)
      Nakajima H, Yamamoto K, Agarwala S, Terai K, Fukui H, Fukuhara S, Ando K, Miyazali T, Yokota Y, Sxhmelzer E, Belting H, Affolter M, Lecaudey, Mochizuki N
    • Journal Title

      Developmental Cell

      Volume: 40 Issue: 6 Pages: 523-536

    • DOI

      10.1016/j.devcel.2017.02.019

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Osteocrin, a secretory peptide from heart, contributes to cranial osteogenesis in zebrafish2016

    • Author(s)
      Chiba A, Watanabe-Takano H, Terai K, Fukui H, Miyazaki T, Uemura M, Hashimoto H, Hibi M, Fukuhara S, Mochizuki N
    • Journal Title

      Development

      Volume: 144 Pages: 334-344

    • DOI

      10.1242/dev.143354

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Clarification of mural cell coverage of vascular endothelial cells by live imaging of zebrafish.2016

    • Author(s)
      Ando K, Fukuhara S, Izumi N, Nakajima H, Fukui H, Kelsh RN, Mochizuki N.
    • Journal Title

      Development

      Volume: 143 Pages: 1328-1339

    • DOI

      10.1242/dev.132654

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] 血流によるメカニカルストレスに依存した新規血管新生機構の解析2018

    • Author(s)
      中嶋洋行、望月直樹
    • Organizer
      第26回日本血管生物医学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Hippo signaling determines the number of atrial cells that originate from the ALPM in zebrafish2018

    • Author(s)
      Hajime Fukui, Julien Vermot, Naoki Mochizuki
    • Organizer
      Weinstein Meeting 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Ang1/Ang2-Tie1/Tie2 signaling for hematovascular development in zebrafish2018

    • Author(s)
      NAOKi MOCHIZUKI
    • Organizer
      IVBM 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] The responses of endothelial cells to the flow2018

    • Author(s)
      Naoki Mochizuki
    • Organizer
      Keystone symposia
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Endothelial YAP is regulated by flow-mediated mechanical stimuli and contributes to vessel stabilization in zebrafish2017

    • Author(s)
      中嶋洋行、望月直樹
    • Organizer
      日本細胞生物学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 骨膜由来steocrin によるNa 利尿ペプチドファミリー分子の機能促進2017

    • Author(s)
      望月直樹 高野晴子 千葉彩乃 宮崎敬大
    • Organizer
      日本内分泌学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Endothelial YAP is regulated by flow-mediated mechanical stimuli through the regulation of F-actin and contributes to vessel maintenance2016

    • Author(s)
      Hiroyuki Nakajima, Naoki Mochizuki
    • Organizer
      The Korea-Japan Vascular Biology Meeting
    • Place of Presentation
      長崎
    • Year and Date
      2016-12-08
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Visualizing mural cell coverage of vascular endothelial cells during zebrafish angiogenesis2016

    • Author(s)
      Naoki Mochizuki
    • Organizer
      The Kloaster Seeon Meeting on Vascular Biology
    • Place of Presentation
      Seeon, Germany
    • Year and Date
      2016-09-17
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Hippoシグナル依存性Bmp4転写調節による二次心臓領域(SHF)心房筋分化制御2016

    • Author(s)
      福井 一、望月直樹
    • Organizer
      第25回日本バイオイメージング学会学術集会
    • Place of Presentation
      名古屋
    • Year and Date
      2016-09-05
    • Related Report
      2016 Annual Research Report
  • [Presentation] スフィンゴシン1-リン酸輸送体による生体機能調節ー循環器発生と免疫についてー2016

    • Author(s)
      望月直樹
    • Organizer
      第58回日本脂質生化学会
    • Place of Presentation
      秋田
    • Year and Date
      2016-06-09
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Remarks] 大阪大学連携大学院循環微小画像医学講座

    • URL

      http://www.z-cv.jp/index.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] 循環微小画像医学ー研究成果

    • URL

      http://www.z-cv.jp/index.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] 国立研究開発法人国立循環器病研究センター研究所細胞生物学部

    • URL

      http://www.z-cv.jp/index.html

    • Related Report
      2016 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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