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The role of Netrin-1 from the ventricular zone in commissural axon guidance

Research Project

Project/Area Number 17K18332
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Nerve anatomy/Neuropathology
Neurophysiology / General neuroscience
Research InstitutionJuntendo University

Principal Investigator

Yamauchi Kenta  順天堂大学, 医学(系)研究科(研究院), 博士研究員 (00513079)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords交連軸索 / ネトリン1 / 軸索誘導 / 脳室帯 / 腹側正中線 / 神経回路形成 / 神経発生 / 軸索ガイダンス
Outline of Final Research Achievements

Based on his observations of commissural axon (CA) growth towards the ventral midline (VM), Ramon y Cajal proposed the ‘chemotropic theory’, attraction of developing axons by a long-range diffusible cue from their targets. Netrin-1 (Ntn1) emanating from the floor plate (FP) has been assumed as the chemoattractant. However, Ntn1 is expressed in the ventricular zone (VZ), in addition to the FP, raising a possibility that Ntn1 of extra-FP origin guides CAs to the VM. In this study, we generated Ntn1 FP conditional mutant (Ntn1FP-Ko) and VZ conditional mutant mice (Ntn1VZ-Ko). If Ntn1 acts CAs as the chemoattractant, CA guidance should be disrupted in Ntn1FP-Ko mice. Contrary to this prediction, deletion of Ntn1 from the VZ highly disrupted CA guidance, whereas deletion of Ntn1 from the FP had little impact on it. Our results fail to support the chemotropic theory, rather suggest a novel mechanism that VZ-derived Ntn1 directs CAs to the VM by its local actions.

Academic Significance and Societal Importance of the Research Achievements

化学走性説に従い交連軸索が腹側正中線へと到達するというモデルはRamon y Cajalによる提唱以来、神経回路形成の基本概念となっていた。本研究の「脳室帯由来Netrin-1が短距離作動性の軸索誘導分子として機能することにより交連軸索を腹側正中線へと誘導する」という結果は神経回路形成の基本概念に再考を迫り、神経軸索再生や細胞移植といった再生医療の樹立へ向けた重要な知見となることが期待できる。

Report

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

    (6 results)

All 2018 2017 Other

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

  • [Int'l Joint Research] Institute of Stem Cell Research(ドイツ)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Institute of Stem Cell Research(Germany)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Netrin-1 Derived from the Ventricular Zone, but not the Floor Plate, Directs Hindbrain Commissural Axons to the Ventral Midline2017

    • Author(s)
      Yamauchi Kenta、Yamazaki Maya、Abe Manabu、Sakimura Kenji、Lickert Heiko、Kawasaki Takahiko、Murakami Fujio、Hirata Tatsumi
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 11992-11992

    • DOI

      10.1038/s41598-017-12269-8

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] The role of Netrin-1 from the ventricular zone in commissural axon guidance2018

    • Author(s)
      Yamauchi Kenta、Yamazaki Maya、Abe Manabu、Sakimura Kenji、Lickert Heiko、Kawasaki Takahiko、Hirata Tatsumi
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Netrin-1 Derived from the Ventricular Zone, but not the Floor Plate, Directs Hindbrain Commissural Axons to the Ventral Midline2018

    • Author(s)
      Yamauchi Kenta、Yamazaki Maya、Abe Manabu、Sakimura Kenji、Lickert Heiko、Kawasaki Takahiko、Murakami Fujio、Hirata Tatsumi
    • Organizer
      第123回日本解剖学会総会・全国学術集会
    • Related Report
      2017 Research-status Report
  • [Remarks] 百年を超えて信じられてきた神経回路形成の基本原理に見直しを迫る

    • URL

      https://www.nig.ac.jp/nig/ja/2017/12/research-highlights_ja/20171128.html

    • Related Report
      2018 Annual Research Report

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Published: 2017-04-28   Modified: 2020-03-30  

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