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Organ-dependent categorization of visceral primary sensory neurons

Research Project

Project/Area Number 17K19527
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Biomedical structure and function and related fields
Research InstitutionKobe University

Principal Investigator

Enomoto Hideki  神戸大学, 医学研究科, 教授 (00360511)

Project Period (FY) 2017-06-30 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords臓器神経回路 / 臓器感覚 / 迷走神経 / 感覚ニューロン / 腸内細菌叢 / 脳腸連関 / 臓器神経 / 腸管神経 / 節状神経節 / 内臓神経系 / 解剖学 / 神経科学 / 細胞・組織 / 生理学
Outline of Final Research Achievements

In this study, we aimed at understanding the anatomy and function of neurons that sense gut luminal environment in the nodose-petrosal ganglia (NPG), which consist of primary sensory neurons in the visceral neural circuit. Based on the assumption that such neurons should respond to microbitota, which is rich in the gut luminal environment, we have performed RNAseq analyses of the NPG of germ-free and SPF mice and compared their gene expression profiles. We have identified a number of genes whose expression levels change in a microbiota-dependent manner, and neuronal subtypes that express those genes. We are currently investigating the function of those genes and neuronal subtypes.

Academic Significance and Societal Importance of the Research Achievements

本研究では臓器一次知覚ニューロンの集合体であるNPGを解析し、腸内細菌叢依存性に発現レベルを変動する遺伝子群とニューロンサブタイプを同定した。腸と脳は神経で繋がり情報伝達していること(脳腸連関)が示されてきたが、どのようなニューロン群がどのような情報を伝達しているのかは未解明である。本研究で同定された遺伝子群やニューロンサブタイプは、この命題を解明するための基盤情報となる。さらに解析を進めることにより、脳腸連関を分子・細胞レベルで理解することが可能となる。また過敏性大腸症候群などの疾患の病態誘導機構解明に繋がることが期待される。

Report

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

    (19 results)

All 2020 2019 2018 2017

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 2 results) Presentation (13 results) (of which Int'l Joint Research: 2 results,  Invited: 5 results)

  • [Journal Article] Point mutagenesis in mouse reveals contrasting pathogenetic effects between MEN2B‐ and Hirschsprung disease‐associated missense mutations of the RET gene2020

    • Author(s)
      Nakatani Taichi、Iwasaki Mitsuhiro、Yamamichi Atsuhiro、Yoshioka Yuta、Uesaka Toshihiro、Bitoh Yuko、Maeda Kosaku、Fukumoto Takumi、Takemoto Tatsuya、Enomoto Hideki
    • Journal Title

      Development, Growth & Differentiation

      Volume: 62 Issue: 4 Pages: 214-222

    • DOI

      10.1111/dgd.12664

    • NAID

      120006863591

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of conditional ALK F1174L mutant mouse models for the study of neuroblastoma pathogenesis.2019

    • Author(s)
      Ono S, Saito T, Terui K, Yoshida H, Enomoto H.
    • Journal Title

      Genesis.

      Volume: 57 Issue: 10 Pages: 1-8

    • DOI

      10.1002/dvg.23323

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mice conditionally expressing RET(C618F) mutation display C cell hyperplasia and hyperganglionosis of the enteric nervous system2019

    • Author(s)
      Okamoto M, Yoshioka Y, Maeda K, Bito Y, Fukumoto T, Uesaka T, Enomoto H
    • Journal Title

      Genesis

      Volume: Epub ahead of print Issue: 5 Pages: 1-8

    • DOI

      10.1002/dvg.23292

    • NAID

      120006996909

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dual origin of enteric neurons in vagal Schwann cell precursors and the sympathetic neural crest2017

    • Author(s)
      Espinosa-Medina Isabel、Jevans Ben、Boismoreau Franck、Chettouh Zoubida、Enomoto Hideki、M?ller Thomas、Birchmeier Carmen、Burns Alan J.、Brunet Jean-Fran?ois
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 114 Issue: 45 Pages: 11980-11985

    • DOI

      10.1073/pnas.1710308114

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Catenins Steer Cell Migration via Stabilization of Front-Rear Polarity2017

    • Author(s)
      Vassilev Vassil、Platek Anna、Hiver Sylvain、Enomoto Hideki、Takeichi Masatoshi
    • Journal Title

      Developmental Cell

      Volume: 43 Issue: 4 Pages: 463-479.e5

    • DOI

      10.1016/j.devcel.2017.10.014

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Striatal hypodopamine phenotypes found in transgenic mice that overexpress glial cell line-derived neurotrophic factor2017

    • Author(s)
      Sotoyama H, Iwakura Y, Oda K, Sasaoka T, Takei N, Kakita A, Enomoto H, Nawa H
    • Journal Title

      Neuroscience Letters

      Volume: 654 Pages: 99-106

    • DOI

      10.1016/j.neulet.2017.06.005

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] RET遺伝子変異によるヒルシュスプルング病誘導機構2020

    • Author(s)
      榎本 秀樹
    • Organizer
      第42回日本分子生物学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Molecular Genetics of Hirschsprung Disease2019

    • Author(s)
      Hideki Enomoto,
    • Organizer
      3rd International Symposium on Congenital Anomaly and Developmental Biology
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 腸管神経系におけるシュワン細胞系譜からのニューロン産生を促す環境要因2019

    • Author(s)
      上坂 敏弘, 榎本 秀樹
    • Organizer
      第95回日本解剖学会近畿支部学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] A point mutation in the Ret gene, RET(S811F), causes Hirschsprung’s disease and kidney agenesis in a dominant-negative fashio2019

    • Author(s)
      Mukhamad Sunardi, Hideki Enomoto
    • Organizer
      第95回日本解剖学会近畿支部学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Enteric neural progenitors sense gut environment to establish structure and function of the enteric nervous system2019

    • Author(s)
      Hideki Enomoto
    • Organizer
      第42回日本分子生物学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] RET 活性化型変異 C618F は遺伝子量減少によりヒルシュスプルング病を誘導する2019

    • Author(s)
      伊藤 圭祐、岡本 光正、上坂 敏弘、前田 貢作、榎本 秀樹
    • Organizer
      CSMIリトリート「若手道場」
    • Related Report
      2018 Research-status Report
  • [Presentation] Elucidation of the anatomy and function of the nodose-petrosal ganglia, a sensory gateway to organ communication2019

    • Author(s)
      Yuta Yoshioka、Hideki Enomoto
    • Organizer
      CSMIリトリート「若手道場」
    • Related Report
      2018 Research-status Report
  • [Presentation] Elevated levels of RET signaling coupled with decreased RET dose causes intestinal aganglionosis in mice2018

    • Author(s)
      Hideki Enomoto
    • Organizer
      Development of the Enteric Nervous System:cells,signals,genes and therapy 5th International Symposium
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Exploration of gene function and genetic interactions in the pathogenesis of Hirschsprung disease by electroporation-mediated genome editing in mice2018

    • Author(s)
      Taichi Nakatani、Mitsuhiro Iwasaki、Yuko Bitoh、 Kosaku Maeda、 Tatsuya Takemoto、 Hideki Enomoto
    • Organizer
      Development of the Enteric Nervous System:cells,signals,genes and therapy 5th International Symposium
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] シュワン細胞に内包された神経分化能とその可塑性2018

    • Author(s)
      榎本 秀樹
    • Organizer
      2018年度生理学研究所研究会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 遺伝性神経芽腫に同定された変異型Phox2Bの機能解析2018

    • Author(s)
      原田 俊介、永島田 まゆみ、岩﨑 光泰、榎本 秀樹
    • Organizer
      第6回神緑会ヤングインベスティゲーターアワード
    • Related Report
      2018 Research-status Report
  • [Presentation] 腸管神経系形成不全下におけるシュワン細胞系譜からのニューロン産生2018

    • Author(s)
      上坂 敏弘、榎本 秀樹
    • Organizer
      第94回日本解剖学会近畿支部学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] RET 活性化型変異 C618F は遺伝子量減少によりヒルシュスプルング病を誘導する2018

    • Author(s)
      伊藤 圭祐、岡本 光正、上坂 敏弘、前田 貢作、榎本 秀樹
    • Organizer
      第94回日本解剖学会近畿支部学術集会
    • Related Report
      2018 Research-status Report

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Published: 2017-07-21   Modified: 2021-02-19  

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