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Elucidation of tissue-specific morphogenetic mechanism regulated by glycolytic activity

Research Project

Project/Area Number 15K07084
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Developmental biology
Research InstitutionDoshisha University

Principal Investigator

Sakai Daisuke  同志社大学, 研究開発推進機構, 助教 (90632646)

Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords解糖系 / 神経管閉鎖 / 低酸素
Outline of Final Research Achievements

To investigate the correlation between hypoxia and embryonic development, we focused on the anaerobic glycolysis, the cellular metabolism under hypoxia. Whole-embryo culture of mid-gestation embryos with glycolytic inhibitors caused neural tube closure defects at cranial levels without cell death. Therefore, anaerobic glycolytic activity seems to be essential for neural plate bending associated with cell shape changes. Consistent with this, we observed suppression of apical constriction and reduction of phosphorylated myosin light chain 2, activator of actin contraction in neuroepithelial cells of inhibitor-treated embryos. Our gene expression analyses demonstrated that some hypoxia-responsive glycolytic enzyme genes were specifically expressed in neural plate of mid-gestation embryos. Taken together, intrauterine hypoxic condition regulates neural plate bending via tissue-specific activation of glycolysis.

Academic Significance and Societal Importance of the Research Achievements

胚の形態形成というイベントは遺伝的プログラムによって進行すると考えられてきた。本研究では、胚を取り巻く環境が遺伝的プログラムを修飾し、形態形成を制御する可能性を検討した。本研究の成果により、子宮内の低酸素環境が細胞内の代謝系の活性化を介して、神経管閉鎖という胚発生過程で最もダイナミックな形態形成過程の一つを制御することが明らかとなった。これにより、新規の環境因子依存的な発生メカニズムの存在が明るみとなった。神経管閉鎖不全は無脳症や二分脊椎症などの先天性障害の原因であり、妊娠期の葉酸欠乏が原因であると考えられている。本研究成果により、解糖系代謝異常もこれらの原因となり得ることが示された。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (12 results)

All 2018 2017 2016 2015

All Journal Article (4 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (7 results) (of which Int'l Joint Research: 2 results,  Invited: 4 results) Book (1 results)

  • [Journal Article] Ventral neural patterning in the absence of a Shh activity gradient from the floorplate2018

    • Author(s)
      Iulianella Angelo, Daisuke Sakai, Hiroshi Kurosaka, Paul Trainor
    • Journal Title

      Developmental Dynamics

      Volume: 247 Issue: 1 Pages: 170-184

    • DOI

      10.1002/dvdy.24590

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Mllt10 knockout mouse model reveals critical role of Af10-dependent H3K79 methylation in midfacial development2017

    • Author(s)
      2.Honami Ogoh, Kazutsune Yamagata, Tomomi Nakao, Lisa L. Sandell, Ayaka Yamamoto, Aiko Yamashita, Naomi Tanga, Mai Suzuki, Takaya Abe, Issay Kitabayashi, Toshio Watanabe, Daisuke Sakai
    • Journal Title

      Scientfic Reports

      Volume: 7 Issue: 1 Pages: 11922-11922

    • DOI

      10.1038/s41598-017-11745-5

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Face off against ROS: Tcof1/Treacle sagegurds neuroepithelial cells and progenitor neural crest cells from oxidative stress during craniofacial development2016

    • Author(s)
      Daisuke Sakai and Paul A Trainor
    • Journal Title

      Development, Growth & Differentiation

      Volume: 58 Issue: 7 Pages: 577-585

    • DOI

      10.1111/dgd.12305

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Prevention of Treacher Collins syndrome craniofacial anomalies in mouse models via maternal antioxidant supplementation2016

    • Author(s)
      Daisuke Sakai, Jill Dixon, Annita Achilleos, Michael Dixon, and Paul A Trainor
    • Journal Title

      Nature Communications

      Volume: 7 Issue: 1 Pages: 10328-10328

    • DOI

      10.1038/ncomms10328

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 多因子性顎顔面奇形疾患の発症機序2018

    • Author(s)
      酒井大輔
    • Organizer
      第42回関西生殖発生毒性フォーラム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Anaerobic glucose metabolism regulates neural tube formation2017

    • Author(s)
      Daisuke Sakai
    • Organizer
      Japanese Society for Developmental Biology
    • Related Report
      2017 Research-status Report
  • [Presentation] 先天性額顔面奇形を出生前に防ぐ2016

    • Author(s)
      酒井大輔
    • Organizer
      日本分子生物学会
    • Place of Presentation
      パジフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] 顎顔面奇形の発症機序と出生前予防2016

    • Author(s)
      酒井大輔
    • Organizer
      日本色素細胞学会
    • Place of Presentation
      岐阜大学サテライトキャンパス(岐阜県岐阜市)
    • Year and Date
      2016-11-12
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Deregulation of histone methylation is implicated in the etiology of frontonasal dysplasia2016

    • Author(s)
      Honami Ogo, Tomomi Nakao, Jun Motoyama, Toshio Watanabe and Daisuke Sakai
    • Organizer
      Gordon Research Conferences 2016, 7th Craniofacial Morphogenesis and Tissue Regeneration
    • Place of Presentation
      Ventura, USA
    • Year and Date
      2016-03-12
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] The role of H3K79 methylation on craniofacial development2015

    • Author(s)
      Honami Ogo, Tomomi Nakao, Issay Kitabayashi, Jun Motoyama, Toshio Watanabe and Daisuke Sakai
    • Organizer
      International Symposium 2015, Oral and Craniofacial Development and Disease,
    • Place of Presentation
      大阪
    • Year and Date
      2015-12-10
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] トリーチャーコリンズ症候群モデルマウスによる顎顔面奇形発症メカニズムの解明2015

    • Author(s)
      酒井大輔
    • Organizer
      第55回 日本先天異常学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2015-07-25
    • Related Report
      2015 Research-status Report
    • Invited
  • [Book] Current Protocols in Essential Laboratory Technique2015

    • Author(s)
      Dennis, R. Warner, Daisuke Sakai, and Lisa, L. Sandell
    • Total Pages
      69
    • Publisher
      John Wiley & Sons
    • Related Report
      2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2020-03-30  

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