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Molecular regulation of directed migration of lymphatic endothelial cells to the craniofacial region in lymphatic vascular development

Research Project

Project/Area Number 17K11631
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Morphological basic dentistry
Research InstitutionThe Nippon Dental University

Principal Investigator

SATO KAORI  日本歯科大学, 生命歯学部, 講師 (90287772)

Co-Investigator(Kenkyū-buntansha) 田谷 雄二  日本歯科大学, 生命歯学部, 准教授 (30197587)
白子 要一  日本歯科大学, 生命歯学部, 助教 (50756377)
添野 雄一  日本歯科大学, 生命歯学部, 教授 (70350139)
Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords歯学 / 病理学 / マウス顎顔面発生 / リンパ管形成 / リンパ管内皮細胞 / ガイダンス因子 / 細胞遊走 / リンパ管発生 / ガイダンス機構 / microRNA / マウス胎仔 / 顎顔面発生 / 遊走能
Outline of Final Research Achievements

We previously found that the craniofacial lymphatic endothelial cells (LECs) originate the venous endothelial cell in cardinal veins of the embryonic mice. This study aimed to investigated how directed migration of LECs from cardinal veins to mandibular arches were regulated. The analyses of immunohistochemistry and histology-based 3D observation revealed the migration route of LECs from the trunk to the craniofacial region, and lymphatic vascular development and the process of lymphatic development in the craniofacial region. In the gene expression analysis, the peak expression levels of Vegfc, which induced the migrating LECs, were shown in the mandibular arches at E13.5-14.5, although Vegfc receptor Vegfr3 and Nrp2 was expressed constitutively. Moreover, we found the reliable molecular cues such as chemokine Cxcl-Cxcr signaling as well as Vegfc that induced the migrating LECs to mandibular arches.

Academic Significance and Societal Importance of the Research Achievements

重篤なリンパ浮腫や癌転移等の種々の病態では、リンパ管新生誘導が病変の成り立ちや予後に大きく作用する要因ともなっている。これらの病態のみならず、リンパ管を標的とした再生医学の観点からも、胎生期でのリンパ管の発生機構を解明することは重要なカギとなる。本研究の成果として、リンパ管発生の仕組み、特にリンパ管内皮細胞の動態や分化の制御機構を明らかにできたことは意義深い。また、本研究で、口腔顎顔面領域でのリンパ管発生の機序を明らかにできたことは、この分野の研究に貢献できたと考えている。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (9 results)

All 2019 2018 2017 Other

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results) Presentation (7 results) (of which Int'l Joint Research: 2 results) Remarks (1 results)

  • [Journal Article] Migration of lymphatic endothelial cells and lymphatic vascular development in the craniofacial region of embryonic mice2018

    • Author(s)
      Taya Y, Sato K, Shirako Y, Soeno Y
    • Journal Title

      Int J Dev Biol

      Volume: 62 Issue: 4-5 Pages: 293-301

    • DOI

      10.1387/ijdb.170218yt

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Craniofacial lymphatic vessels are formed by endothelial cells migrated from truncal cardinal veins2019

    • Author(s)
      Yuji Taya, Kaori Sato, Youichi Shirako, Yuuichi Soeno
    • Organizer
      Society for Developmental Biology 78th Annual Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] マウス顎顔面発生における舌下神経軸索と舌筋細胞系譜との相互作用2019

    • Author(s)
      田谷雄二、佐々木康成、堀江哲郎、佐藤かおり、添野雄一:
    • Organizer
      第61回歯科基礎医学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] How can the hypoglossal neuroaxis elongate to tongue muscle in mice?2019

    • Author(s)
      Yuji Taya, Yasunori Sasaki, Tetsuro Horie, Kaori Sato, Yuuichi Soeno
    • Organizer
      令和元年度日本歯科大学歯学会第6回ウィンターミーティング
    • Related Report
      2019 Research-status Report
  • [Presentation] How are lymphatic vessels formed in the oral region of embryos?2019

    • Author(s)
      Yuji Taya, Kaori Sato, Youichi Shirako, Yuuichi Soeno
    • Organizer
      令和元年度日本歯科大学歯学会大会・総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Lymphatic vascular development in the craniofacial region of embryonic mice ― Migration of lymphatic endothelial cells from cardinal veins into mandibular arches ―2018

    • Author(s)
      Taya Y, Sato K, Shirako Y, Soeno Y
    • Organizer
      Joint Annual Meeting of 51st JSDB and 70th JSCB
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] マウス顎顔面領域へのリンパ管内皮細胞の移住とリンパ管形成2018

    • Author(s)
      田谷雄二,佐藤かおり,白子要一,添野雄一
    • Organizer
      第60回歯科基礎医学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Lymphangiogenic dynamics in oral cancer microenvironment2017

    • Author(s)
      Shirako Y, Taya Y, Sato K, Soeno Y
    • Organizer
      平成29年度日本歯科大学歯学会第4回ウィンターミーティング
    • Related Report
      2017 Research-status Report
  • [Remarks] 日本歯科大学病理学講座HP

    • URL

      http://www.ndu.ac.jp/~pathhome/

    • Related Report
      2020 Annual Research Report 2019 Research-status Report 2018 Research-status Report 2017 Research-status Report

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Published: 2017-04-28   Modified: 2022-01-27  

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