• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Investigation of the role of axon guidance in the enteric nervous system for novel therapeutic approach for Hirschsprung's disease.

Research Project

Project/Area Number 16K20347
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pediatric surgery
Research InstitutionJuntendo University

Principal Investigator

FUJIWARA NAHO  順天堂大学, 医学部, 非常勤講師 (20589543)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsヒルシュスプルング病 / 神経ガイダンス因子 / セマフォリン3A / セマフォリン3A / 細胞移植 / 細胞培養
Outline of Final Research Achievements

Semaphorin 3A (SEMA3A) is a secreted type of semaphorins that is recognized as the most potent repulsive or repelling neurite outgrowth of central and peripheral nervous system. Pregnant SOX10-VENUS+/EDNRB mice were sacrificed on days 13.5 and 15.5 of gestation (E13.5 and E15.5, respectively). Immunofluorescent analyses using DAPI, Venus, and SEMA3A were performed to evaluate protein expression/distribution of SEMA3A. Slides were then examined using laser scanning microscopy. There was markedly increased muscle layer SEMA3A immunoreactivity observed In EDNRB null mice specimens (both E13.5 and E15.5) compared with control mice Our results provide the first evidence that SEMA3A expression is increased in the EDNRB null mouse HD model (both E13.5 and E15.5), suggesting that increased expression of SEMA3A may interfere with ENCC development, resulting in absence of enteric neurons.

Academic Significance and Societal Importance of the Research Achievements

本研究において、H病腸管では正常腸管よりも有意にSEMA3Aの発現が高いことが示され、SEMA3Aがこの時期の腸管神経の発生過程に何らかの影響を及ぼしていることが示唆された。さらに正常とH病腸管神経の発生過程での相違を細胞レベルで検証することを目的に細胞培養技術を導入した。SOX10-VENUS陽性の神経堤由来細胞のみをFACSを用いて選択し、培養を行った。そして、神経堤由来細胞からglia細胞への分化の程度が正常とH病腸管では異なることを明らかにし、その結果を発表した。これらの結果により、新しい技術を導入し、H病での腸管神経発生過程の相違について理解を深めることが出来たと考えている。

Report

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

    (20 results)

All 2018 2017 2016

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (15 results) (of which Int'l Joint Research: 11 results)

  • [Journal Article] Altered expression of laminin alpha1 in aganglionic colon of endothelin receptor-B null mouse model of Hirschsprung's disease.2018

    • Author(s)
      Fujiwara N, Nakazawa-Tanaka N, Miyahara K, Arikawa-Hirasawa E, Akazawa C, Yamataka A
    • Journal Title

      Pediatr Surg Int

      Volume: 34 Issue: 2 Pages: 137-141

    • DOI

      10.1007/s00383-017-4180-6

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] The effect of laminin-1 on enteric neural crest-derived cell migration in the Hirschsprung's disease mouse model2018

    • Author(s)
      Nakazawa-Tanaka N, Fujiwara N, Miyahara K, Nakada S, Arikawa-Hirasawa E, Akazawa C, Yamataka A
    • Journal Title

      Pediatr Surg Int

      Volume: 34 Issue: 2 Pages: 143-147

    • DOI

      10.1007/s00383-017-4181-5

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Increased expression of Semaphorin 3A in the endothelin receptor-B null mouse model of Hirschsprung disease2018

    • Author(s)
      Fujiwara Naho、Miyahara Katsumi、Nakazawa-Tanaka Nana、Akazawa Chihiro、Yamataka Atsuyuki
    • Journal Title

      Journal of Pediatric Surgery

      Volume: 53 Issue: 2 Pages: 326-329

    • DOI

      10.1016/j.jpedsurg.2017.11.034

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Altered differentiation of enteric neural crest-derived cells from endothelin receptor-B null mouse model of Hirschsprung's disease.2016

    • Author(s)
      Fujiwara N, Miyahara K, Nakazawa-Tanaka N, Akazawa C, Yamataka A.
    • Journal Title

      Pediatric Surgery International

      Volume: 32 Issue: 12 Pages: 1095-1101

    • DOI

      10.1007/s00383-016-3964-4

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Three- and four-dimensional analysis of altered behavior of enteric neural crest derived cells in the Hirschsprung's disease mouse model2016

    • Author(s)
      Nakazawa-Tanaka N, Miyahara K, Fujiwara N, Urao M, Akazawa C, Yamataka A
    • Journal Title

      Pediatr Surg Int

      Volume: 32 Issue: 1 Pages: 390-407

    • DOI

      10.1007/s00383-015-3806-9

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 腸管神経系の発生におけるラミニンの神経軸索伸長作用の検討2018

    • Author(s)
      藤原なほ
    • Organizer
      第55回小児外科学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Transplanted SOX10-Venus mouse enteric neural crest-derived cells colonise the aganglionic colon in the Hirschsprung’s mouse model2018

    • Author(s)
      Fujiwara N, Miyahara K, Nakazawa-Tanaka N, Akazawa C, Yamataka A
    • Organizer
      The 19th European Congress of Pediatric Surgery
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Transplanted SOX10-Venus mouse enteric neural crest-derived cells colonise the aganglionic colon in the Hirschsprung’s mouse model2018

    • Author(s)
      Fujiwara N, Miyahara K, Nakazawa-Tanaka N, Akazawa C, Yamataka A
    • Organizer
      25th International Meeting of the Pediatric Colorectal Club
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Transplanted SOX10-Venus mouse enteric neural crest-derived cells colonise the aganglionic colon in the Hirschsprung’s mouse model2018

    • Author(s)
      Fujiwara N, Miyahara K, Nakazawa-Tanaka N, Akazawa C, Yamataka A
    • Organizer
      31st International Symposium on Paediatric Surgical Research
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] LAMININ PROMOTES NEURITE GROWTH IN THE ENTERIC NERVOUS SYSTEM OF THE EMBRYONIC MOUSE GUT2017

    • Author(s)
      Fujiwara N., Miyahara K., Nakazawa-Tanaka N., Akazawa C., Yamataka A.
    • Organizer
      18th Congress of the European Paediatric Surgeons’ Association
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] ALTERED DIFFERENTIATION OF ENTERIC NEURAL CREST DERIVED CELLS FROM ENDOTHELIN-B RECEPTOR NULL MOUSE MODEL OF HIRSCHSPRUNG’S DISEASE2017

    • Author(s)
      Fujiwara N., Miyahara K., Nakazawa-Tanaka N., Akazawa C., Yamataka A.
    • Organizer
      Pediatric Colorectal Club 24th International Meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Increased expression of Semaphorin 3A in the endothelin receptor-B null mouse model of Hirschsprung disease.2017

    • Author(s)
      Fujiwara N, Miyahara K, Nakazawa-Tanaka N, Akazawa C, Yamataka
    • Organizer
      The 65th Annual Congress, British Association of Paediatric Surgeons
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] ALTERED EXPRESSION OF LAMININ ALPHA1 IN AGANGLIONIC COLON OF ENDOTHELIN RECEPTOR-B NULL MOUSE MODEL OF HIRSCHSPRUNG’S DISEASE2017

    • Author(s)
      N. Fujiwara, N. Nakazawa-Tanaka, K. Miyahara, E. Arikawa-Hirasawa, C. Akazawa, A. Yamataka
    • Organizer
      30thINTERNATIONAL SYMPOSIUM ON PEDIATRIC SURGICAL RESEARCH, AND AN UPDATE ON NEWBORN AND FETAL SURGERY
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] THE EFFECT OF LAMININ-1 ON ENTERIC NEURAL CREST DERIVED CELLS MIGRATION IN THE HIRSCHSPRUNG’S DISEASE MOUSE MODEL2017

    • Author(s)
      N. Nakazawa-Tanaka, N. Fujiwara, K. Miyahara, S. Nakada, E. Arikawa-Hirasawa, C. Akazawa, M. Urao, A. Yamataka
    • Organizer
      30thINTERNATIONAL SYMPOSIUM ON PEDIATRIC SURGICAL RESEARCH, AND AN UPDATE ON NEWBORN AND FETAL SURGERY
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Altered differentiation of enteric neural crest-derived cells from endothelin receptor-B null mouse model of Hirschsprung's disease.2016

    • Author(s)
      Naho Fujiwara
    • Organizer
      The 28th International Symposium on Paediatric Surgical Research
    • Place of Presentation
      Germany
    • Year and Date
      2016-09-08
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Semaphorin 3A expression upregulated in the EDNRB(-/) mouse model of Hirschsprung's disease.2016

    • Author(s)
      Naho Fujiwara
    • Organizer
      17th European Paediatric Surgeons Association's Annual Congress
    • Place of Presentation
      Italy
    • Year and Date
      2016-06-15
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Increased expression of Semaphorin3A in the Endothelin-B null mouse model of Hirschsprung's disease.2016

    • Author(s)
      Naho Fujiwara
    • Organizer
      23rd International Meeting of the Pediatric Colorectal Club
    • Place of Presentation
      Prague
    • Year and Date
      2016-06-14
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Hirschsprung病モデルマウス腸管を用いた神経ガイダンス因子セマフォリン3A(SEMA3A)の発現の検討2016

    • Author(s)
      藤原なほ
    • Organizer
      第53回 日本小児外科学会学術集会
    • Place of Presentation
      福岡
    • Year and Date
      2016-05-24
    • Related Report
      2016 Research-status Report
  • [Presentation] Hirschsprung病モデルマウス腸管を用いた神経ガイダンス因子セマフォリン3A(SEMA3A)の発現の検討2016

    • Author(s)
      藤原なほ
    • Organizer
      第116回日本外科学会定期学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2016-04-15
    • Related Report
      2016 Research-status Report
  • [Presentation] 神経ガイダンス因子の腸管神経系における役割解明とヒルシュスプルング病に対する新しい再生治療法の開発2016

    • Author(s)
      藤原なほ
    • Organizer
      第116回日本外科学会定期学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2016-04-15
    • Related Report
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi