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Studies on roles of mechanical forces in the pathogenesis of perinatal diseases

Research Project

Project/Area Number 15K15408
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Embryonic/Neonatal medicine
Research InstitutionOsama Woman's and Children's Hospital

Principal Investigator

Matsuo Isao  地方独立行政法人大阪府立病院機構大阪母子医療センター(研究所), 病因病態部門, 部長 (10264285)

Research Collaborator Yoshida Chiharu  
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords発生・分化 / 先天性疾患 / メカニカルフォース / 神経管閉鎖不全 / ノンカノニカルWnt / 平面内極性 / 表皮 / 原子間力顕微鏡 / 周産期疾患 / 着床障害 / 先天異常 / 平面内細胞極性 / 哺乳動物胚 / 物理的特性 / ヤング率 / 神経管閉鎖 / メカノセンシング / 幹細胞
Outline of Final Research Achievements

Neural tube defects (NTDs), one of the most common congenital disorders are thought to be caused by environmental factors during pregnancy, genetic factors, and the combination of both factors. However, the precise mechanisms underlying the pathogenesis of NTDs remain to be understood. The current project hypothesized that the “loss of robustness or strength in surface ectoderm against mechanical stress during neural tube closure is a primary cause of NTDs pathogenesis”. The mechanical properties of surface ectoderm in wild-type and Grhl3 mutant mouse embryos showing NTDs were measured by atomic force microscopy and the mechanical strength of Grhl3-deficient embryos were shown to be decreased compared to that of wild-type embryos. In addition, Grhl3-induced mechanical strength of surface ectoderm was mediated by the noncanonical Wnt pathway including planar cell polarity genes.

Academic Significance and Societal Importance of the Research Achievements

先天性疾患の発症原因は、遺伝因子や環境因子とその両方の組み合わせによると考えられているが、半数近くは依然として不明である。今回の研究成果は、表皮の物理的強度が低下することで神経管閉鎖不全発症の原因となっている可能性を示唆するものである。更に、本研究成果は、神経管閉鎖障害以外の他の先天性疾患についても、組織や細胞の物理的な強度の異常が、病態発症に関与している可能性を示唆している。今後、本研究結果を基盤に研究を発展させることで、より一般化した仮説の検証を進めていくことが期待される。

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

    (24 results)

All 2019 2018 2017 2016 2015 Other

All Int'l Joint Research (4 results) Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 4 results,  Acknowledgement Compliant: 2 results) Presentation (10 results) (of which Int'l Joint Research: 2 results,  Invited: 4 results) Remarks (4 results)

  • [Int'l Joint Research] INSERM(フランス)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] INSERM(FRANCE)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] Division of Molecular Embryology/DKFZ-ZMBH Alliance(Germany)

    • Related Report
      2015 Research-status Report
  • [Int'l Joint Research] Institute of Molecular Biology(Germany)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Competition for Mitogens Regulates Spermatogenic Stem Cell Homeostasis in an Open Niche2019

    • Author(s)
      Kitadate Y., Jorg DJ., Tokue M,. Maruyama A., Ishikawa R., Tsuchiya S., Segi-Nishida E., Nakagawa T., Uchida A., Kimura-Yoshida C., Mizuno S., Sugiyama F., Azami T., Ema M., Noda C., Kobayashi S., Matsuo I., Kanai Y., Nagasawa T., Sugimoto Y., Takahashi S., Simons BD., Yoshida S.
    • Journal Title

      Cell Stem Cell

      Volume: 24 Issue: 1 Pages: 79-92

    • DOI

      10.1016/j.stem.2018.11.013

    • NAID

      120007128265

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cytoplasmic localization of GRHL3 upon epidermal differentiation triggers cell shape change for epithelial morphogenesis2018

    • Author(s)
      Chiharu Kimura-Yoshida, Kyoko Mochida, Masa-aki Nakaya, Takeomi Mizutani and Isao Matsuo
    • Journal Title

      Nature Communications

      Volume: 9(1) Issue: 1 Pages: 4059-4059

    • DOI

      10.1038/s41467-018-06171-8

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] マウス胚前後軸形成において力学的環境が果たす役割2018

    • Author(s)
      松尾 勲
    • Journal Title

      大阪母子医療センター雑誌

      Volume: 34(1) Pages: 1-11

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanical perspectives on the anterior-posterior axis polarization of mouse implanted embryos2017

    • Author(s)
      Matsuo I., and Hiramatsu R.
    • Journal Title

      Mech Dev.

      Volume: 144(Pt A) Pages: 62-70

    • DOI

      10.1016/j.mod.2016.09.002

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Coordinately Co-opted Multiple Transposable Elements Constitute an Enhancer for wnt5a Expression in the Mammalian Secondary Palate.2016

    • Author(s)
      Nishihara H., Kobayashi N., Kimura-Yoshida C., Yan K., Bormuth O., Ding Q., Nakanishi A., Sasaki T., Hirakawa M., Sumiyama K., Furuta Y., Tarabykin V., Matsuo I., and Okada N.
    • Journal Title

      PLoS Genet.

      Volume: 12(10) Issue: 10 Pages: 1-17

    • DOI

      10.1371/journal.pgen.1006380

    • NAID

      120005997729

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Fate Specification of Neural Plate Border by Canonical Wnt Signaling and Grhl3 is Crucial for Neural Tube Closure2015

    • Author(s)
      Chiharu Kimura-Yoshida, Kyoko Mochida, Kristina Ellwanger, Christof Niehrs, Isao Matsuo
    • Journal Title

      EBioMedicine

      Volume: 未定 Issue: 6 Pages: 513-527

    • DOI

      10.1016/j.ebiom.2015.04.012

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] マウス着床後胚におけるライヘルト膜の力学的機能の解析2018

    • Author(s)
      上田 陽子、吉田 千春、爪 麻美、持田 京子、松尾 勲
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] GRHL3因子は核から細胞質へ局在を変えることで、機能的で弾性率に富んだ上皮細胞を誘導する2018

    • Author(s)
      木村-吉田 千春、持田 京子、中谷 雅明、水谷 武臣、松尾 勲
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] GRHL3 triggers epithelial morphogenesis from differentiation in uncommitted ectodermal progenitors during neural tube2018

    • Author(s)
      Chiharu Kimura-Yoshida, Kyoko Mochida, Takeomi Mizutani, Isao Matsuo
    • Organizer
      International Young Scientists Workshop on Neural Development & Stem Cells 2018
    • Related Report
      2017 Research-status Report
  • [Presentation] Surface ectoderm specification of uncommitted ectodermal progenitors in the neural plate border is crucial for neural tube closure2017

    • Author(s)
      Chiharu Kimura-Yoshida, Isao Matsuo
    • Organizer
      50th Annual Meeting for the Japanese Society of Developmental Biologists
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 神経管閉鎖時におけるGrainyhead-like 3遺伝子発現表皮細胞の機能解析2017

    • Author(s)
      木村ー吉田千春、持田京子、水谷武臣、松尾勲
    • Organizer
      2017年度生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Research-status Report
  • [Presentation] マウス神経管閉鎖過程におけるGrainyhead-like 3の機能解析2017

    • Author(s)
      松尾 勲、木村ー吉田 千春
    • Organizer
      Wnt研究会2017
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Fate specification of neural plate border by canonical Wnt signaling and Grhl3 is crucial for mammalian neural tube closure2016

    • Author(s)
      Chiharu Kimura-Yoshida, Kyoko Mochida, Kristina Ellwanger, Christof Niehrs, and Isao Matsuo
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 神経管閉鎖過程におけるカノニカルWnt経路とGrhl3 遺伝子を介した未分化前駆細胞から表皮への細胞運命決定機構2015

    • Author(s)
      木村-吉田 千春、持田 京子、Kristina Ellwanger、Christof Niehrs、松尾 勲
    • Organizer
      BMB2015 第38回日本分子生物学会年会 第88回日本生化学会大会
    • Place of Presentation
      神戸ポートアイランド(兵庫県・神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] カルポニン3ノックアウトマウスの表現型解析2015

    • Author(s)
      渋川 幸直、山崎 奈津子、大門 江津子、木村-吉田 千春、持田 京子、松尾 勲、和田 芳直
    • Organizer
      BMB2015 第38回日本分子生物学会年会 第88回日本生化学会大会
    • Place of Presentation
      神戸ポートアイランド(兵庫県・神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] Mechanical interaction among embryonic, extraembryonic and maternal tissues for the anterior-posterior axis formation in mouse embryos2015

    • Author(s)
      Ryuji Hiramatsu and Isao Matsuo
    • Organizer
      EMBO work shop “Embyonic-Extraembryonic Interfaces”
    • Place of Presentation
      Goettingen (Germany)
    • Year and Date
      2015-05-06
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Remarks] 地方独立行政法人大阪府立病院機構大阪母子医療センター研究所ホームページ

    • URL

      https://www.wch.opho.jp/research/index.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] 大阪母子医療センター研究所病因病態部門

    • URL

      http://www.mch.pref.osaka.jp/research/embryology/index.html

    • Related Report
      2017 Research-status Report
  • [Remarks] 地方独立行政法人 大阪府立病院機構 大阪母子医療センター 研究所 病因病態部門

    • URL

      http://www.mch.pref.osaka.jp/research/embryology/index.html

    • Related Report
      2016 Research-status Report
  • [Remarks] 大阪府立母子保健総合医療センター研究所病因病態部門

    • URL

      http://www.mch.pref.osaka.jp/research/embryology/index.html

    • Related Report
      2015 Research-status Report

URL: 

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

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