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The role of Shh in tongue development

Research Project

Project/Area Number 16K11744
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Surgical dentistry
Research InstitutionTokyo Medical and Dental University

Principal Investigator

OKUHARA Shigeru  東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (10451973)

Co-Investigator(Kenkyū-buntansha) 井関 祥子  東京医科歯科大学, 大学院医歯学総合研究科, 教授 (80251544)
森田 圭一  東京医科歯科大学, 大学院医歯学総合研究科, 講師 (10396971)
長岡 亮介  東京医科歯科大学, 歯学部附属病院, 特任助教 (30760805)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords舌 / 腱 / 内舌筋 / Sonic hedgehog / Shh / 口蓋裂 / SHH
Outline of Final Research Achievements

Tongue is a specialized organ for airway, phonetic articulation, oral sensation, mastication and swallowing. At the beginning of tongue development, tongue is filled with the neural crest cells and gradually muscle cells immigrate to be the majority. In this study, by utilizing the spatiotemporal deletion mutant for Sonic hedgehog, which has a defective tongue, we have explored the tongue development. The mutant show defective tongue including the dysorganized patterning of the intrinsic muscle and highly defective tendon. We have also shown that SHH is received not by muscle/myoblast but by the neural crest cells utilizing the other mutant mice.
In total, the neural crest cells receive SHH to differentiate into tendon, which allows the organized patterning of the muscle, which further allows the complex motion of the tongue. Our result may have shown the insight of the abnormality of the tongue motion in humans.

Academic Significance and Societal Importance of the Research Achievements

まず、舌発生過程を明らかにし、筋が大半を占める舌ではあるが、神経堤細胞が腱となって筋を正しく配置して舌が発生することを示した。これは、ヒトで舌の形態や運動の異常を呈する病態、例えばクローバーリーフ舌などの病態に相当するので、その病態を解明したと言える。特に、遺伝子欠失モデルマウスを用いて病態にかかわる発生学的な機序を明らかにしたので、モデルマウスで欠失しているSHH遺伝子とその発現を制御するエンハンサー領域の変異により、あるいは腱発生に関わる機序の異常によっても、ヒトで舌の形態・運動異常を伴って発生する可能性があることを示すことができた。

Report

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

    (7 results)

All 2018 2016 Other

All Int'l Joint Research (3 results) Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Int'l Joint Research] King's College London(英国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] King's Collage, London(英国)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] King's College London(英国)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Transcription factor Foxc1 is involved in anterior part of cranial base formation.2018

    • Author(s)
      Mya N, Furutera T, Okuhara S, Kume T, Takechi M, Iseki S.
    • Journal Title

      Conget. Anom.

      Volume: - Issue: 5 Pages: 158-166

    • DOI

      10.1111/cga.12268

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 口蓋上皮 TGF-β および Shh は,口蓋間葉の Tenascin C 発現を誘導する2018

    • Author(s)
      大木 調,岡 暁子,緒方佳代子,中村 雅子,奥原 滋,尾崎 正雄,井関 祥子,阪井 丘芳
    • Organizer
      第60回歯科基礎医学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Sonic hedgehog is required for neural crest-dependent patterning of the intrinsic tongue musculature2018

    • Author(s)
      Shigeru Okuhara Anahid A. Birjandi, Hadeel Adel Al-Lami, Tomoko Sagai, Takanori Amano, Toshihiko Shiroishi, Karen J. Liu, Martyn T. Cobourne
    • Organizer
      Gordon Research Conference Craniofacial Morphogenesis and Tissue Regeneration
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Shh signaling during patterning of the murine tongue2016

    • Author(s)
      Shigeru OKUHARA, Tomoko Sagai, Anahid A. Birjandi2Hadeel Al-Lami, Tomoko Sagai, Takanori Amano, Toshihiko Shiroishi, Karen Liu, Martyn T. Cobourne, Sachiko Iseki
    • Organizer
      JSDB Special Symposium: Frontier of Developmental Biology
    • Place of Presentation
      東京大学小柴ホール(東京都・文京区)
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2022-02-22  

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