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Molecular basis of glossopharyngeal nerve formation during pahryngeal arch development

Research Project

Project/Area Number 26460257
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General anatomy (including histology/embryology)
Research InstitutionKitasato University

Principal Investigator

Okubo Tadashi  北里大学, 医学部, 准教授 (10450719)

Project Period (FY) 2014-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2014: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Keywords舌咽神経 / Ripply3 / 咽頭弓 / 味蕾形成 / レチノイン酸シグナル / プロモーター制御 / 舌咽神経節 / レチノイン酸 / 咽頭弓分節 / ゲノム編集 / Tbx1 / 転写抑制因子 / epibranchial placode / 神経分化
Outline of Final Research Achievements

Pharyngeal arch (PA) is a transient segmental structure, and it is important for the later peripheral neurogenesis. Ripply3 is highly expressed in the developing PA of mouse. To explore the regulatory mechanism underlying between PA formation and glossopharyngeal nerve (GN) development, we focused on the involvement of Ripply3. Consequently, we found Ripply3 is required for GN development. Next, we identified retinoic acid (RA) is required for the enhancement of Ripply3 expression. Ripply3 promoter analysis revealed that RA and Ripply3 cooperatively participate in PA and GN development. We also found that Ripply3 expressing cells give rise to GN ganglia by using cre reporter system. Some candidates of Ripply3 interacting genes were identified. Among them, Paxilin is involved in morphogenesis of PA with Ripply3, and Glyr1 is a novel factor regulates the transcriptional property of Ripply3. Thus, we gained new insights into the Ripply3 function in GN formation during PA development.

Academic Significance and Societal Importance of the Research Achievements

脊椎動物の胎児期に現れる咽頭弓は、その後様々器官形成に関与する。ヒトのDiGeorge症候群ではTBX1の欠失により咽頭弓の形成不全に続く心臓、胸腺そして末梢神経の形成異常が起こる。我々は、これまでにマウスTbx1の転写抑制因子としてRipply3を同定し、咽頭弓分節に必須な遺伝子であることを報告したが、Ripply3が舌咽神経の形成に関与しているか不明であった。本研究は、Ripply3と咽頭弓分節、舌咽神経節形成との連関を明らかにし、その背後にある分子機構の一端を解明するに至った。また近年ヒトRIPPLY3にも変異が見つかっており、ヒト先天性異常の発症機構を理解する上で重要な研究といえる。

Report

(7 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (12 results)

All 2019 2018 2017 2016 2015 2014

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (9 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] Differential behavioral phenotypes of Dopamine D1 receptor knockdown mice at the embryonic, postnatal, and adult stages2018

    • Author(s)
      Okubo T, Sato A, Okamoto H, Sato T, Sasaoka T.
    • Journal Title

      International Journal of Developmental Neuroscience

      Volume: 66 Issue: 1 Pages: 1-8

    • DOI

      10.1016/j.ijdevneu.2017.11.004

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pharyngeal Arch Deficiencies Affect Taste Bud Development in the Circumvallate Papilla With Aberrant Glossopharyngeal Nerve Formation2015

    • Author(s)
      Tadashi Okubo, Shinji Takada
    • Journal Title

      Developmental Dynamics

      Volume: 244 Issue: 7 Pages: 874-887

    • DOI

      10.1002/dvdy.24289

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Insm1 promotes endocrine cell differentiation by modulating the expression of a network of genes that includes Neurog3 and Ripply3.2014

    • Author(s)
      Osipovich AB, Long Q, Manduchi E, Gangula R, Hipkens SB, Schneider J, Okubo T, Stoeckert CJ Jr, Takada S, Magnuson MA
    • Journal Title

      Development

      Volume: 141 Issue: 15 Pages: 2939-2949

    • DOI

      10.1242/dev.104810

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] The effect of retinoic acid signaling on the expression of Ripply3 gene in pharyngeal arch development2019

    • Author(s)
      Tadashi Okubo, Keiko Hara, Sadahiro Azuma, Shinji Takada
    • Organizer
      第52回 日本発生生物学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] WRPW motif of Ripply3 is essential for the outflow tract formation2018

    • Author(s)
      Okubo T, Hara K, Kajiyama Y. Takada S
    • Organizer
      Weinstein 2018 Cardiovascular development and regeneration conference
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] WRPW motif of Ripply3 is essential for the outflow tract formation2018

    • Author(s)
      Okubo T, Hara K, Kajiyama Y. Takada S
    • Organizer
      日本分子生物学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Adapter protein Ripply3 is required for epithelial morphogenesis in the mouse pharyngeal pouch. 18th International Congress of Developmental Biology2017

    • Author(s)
      Tsuchiya Y, Okubo T, Mii Y, Takada S
    • Organizer
      The 18th congress of the International Society of Developmental Biologist
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Ripply3 expressing cells give rise to epibranchial placode derived ganglia and vestibulocochlear ganglia2017

    • Author(s)
      Okubo T, Hara K, Kano M, and Takada S
    • Organizer
      日本発生生物学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Adaptor protein Ripply3 is required for epithelial morphogenesis in the mouse pharyngeal pouch2016

    • Author(s)
      土屋凱寛、大久保直、三井優輔、高田慎治
    • Organizer
      日本発生生物学会秋期シンポジウム
    • Place of Presentation
      三島市民文化会館(静岡県三島市)
    • Year and Date
      2016-10-19
    • Related Report
      2016 Research-status Report
  • [Presentation] Lineage analysis of Ripply3 expressing cells during the mouse development2015

    • Author(s)
      Tadashi Okubo, Shinji Takada
    • Organizer
      日本分子生物学会
    • Place of Presentation
      神戸ポートアイランド(兵庫県神戸市)
    • Year and Date
      2015-12-02
    • Related Report
      2015 Research-status Report
  • [Presentation] 咽頭弓分節化と胸腺形成の分子基盤の解明に向けて2015

    • Author(s)
      大久保直、土屋凱寛、高田慎治
    • Organizer
      第34回 日本胸腺研究会 ミニシンポジウム
    • Place of Presentation
      ユニコムプラザさがみはら(神奈川県・相模原市)
    • Year and Date
      2015-02-07
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 咽頭弓の分節化におけるscaffoldタンパク質WTIPの解析2014

    • Author(s)
      土屋凱寛、大久保直、三井優輔、高田慎治
    • Organizer
      第37回 日本分子生物学会総会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2014-11-26
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2021-02-19  

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