Repulsive Sema3E-Plexin-D1 signaling coordinates both axonal extension and steering via activating an autoregulatory factor, Mtss1

  1. Namsuk Kim
  2. Yan Li
  3. Ri Yu
  4. Hyo-Shin Kwon
  5. Anji Song
  6. Mi-Hee Jun
  7. Jin-Young Jeong
  8. Ji Hyun Lee
  9. Hyun-Ho Lim
  10. Mi-Jin Kim
  11. Jung-Woong Kim
  12. Won-Jong Oh  Is a corresponding author
  1. Korea Brain Research Institute, Republic of Korea
  2. Korea Brain Research Institute, Korea (South), Republic of
  3. Chung-Ang University, Republic of Korea

Abstract

Axon guidance molecules are critical for neuronal pathfinding because they regulate directionality and growth pace during nervous system development. However, the molecular mechanisms coordinating proper axonal extension and turning are poorly understood. Here, Metastasis Suppressor 1 (Mtss1), a membrane protrusion protein, ensured axonal extension while sensitizing axons to the Semaphorin 3E (Sema3E)-Plexin-D1 repulsive cue. Sema3E-Plexin-D1 signaling enhanced Mtss1 expression in projecting striatonigral neurons. Mtss1 localized to the neurite axonal side and regulated neurite outgrowth in cultured neurons. Mtss1 also aided Plexin-D1 trafficking to the growth cone, where it signaled a repulsive cue to Sema3E. Mtss1 ablation reduced neurite extension and growth cone collapse in cultured neurons. Mtss1-knockout mice exhibited fewer striatonigral projections and irregular axonal routes and these defects were recapitulated in Plxnd1- or Sema3e-knockout mice. These findings demonstrate that repulsive axon guidance activates an exquisite autoregulatory program coordinating both axonal extension and steering during neuronal pathfinding.

Data availability

The accession number for the RNA-Seq data reported in the present study is GSE196558.

The following data sets were generated

Article and author information

Author details

  1. Namsuk Kim

    Korea Brain Research Institute, Daegu, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5043-0293
  2. Yan Li

    Korea Brain Research Institute, Daegu, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  3. Ri Yu

    Korea Brain Research Institute, Daegu, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  4. Hyo-Shin Kwon

    Korea Brain Research Institute, Daegu, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  5. Anji Song

    Korea Brain Research Institute, Daegu, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  6. Mi-Hee Jun

    Korea Brain Research Institute, Daegu, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  7. Jin-Young Jeong

    Korea Brain Research Institute, Daegu, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  8. Ji Hyun Lee

    Korea Brain Research Institute, Daegu, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  9. Hyun-Ho Lim

    Structure and Function of Neural Network, Korea Brain Research Institute, Daegu, Korea (South), Republic of
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5477-5640
  10. Mi-Jin Kim

    Chung-Ang University, Seoul, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  11. Jung-Woong Kim

    Chung-Ang University, Seoul, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  12. Won-Jong Oh

    Korea Brain Research Institute, Daegu, Republic of Korea
    For correspondence
    ohwj@kbri.re.kr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8867-7814

Funding

Korea Brain Research Institute (KBRI 23-BR-01-02)

  • Won-Jong Oh

National Research Foundation of Korea (NRF-2014R1A1A2058234)

  • Won-Jong Oh

National Research Foundation of Korea (NRF-2020M3E5D9079766)

  • Won-Jong Oh

National Research Foundation of Korea (NRF-2022M3E5E8017701)

  • Won-Jong Oh

National Research Foundation (Young Researcher Program 2020R1C1C1010509)

  • Namsuk Kim

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All protocols for animal experiments were approved by the Institutional Animal Care and Use Committee of Korea Brain Research Institute (IACUC-18-00008, 20-00012). All experiments were performed according to the National Institutes of Health Guide for the Care and Use of Laboratory Animals and ARRIVE guidelines.

Copyright

© 2024, Kim et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Namsuk Kim
  2. Yan Li
  3. Ri Yu
  4. Hyo-Shin Kwon
  5. Anji Song
  6. Mi-Hee Jun
  7. Jin-Young Jeong
  8. Ji Hyun Lee
  9. Hyun-Ho Lim
  10. Mi-Jin Kim
  11. Jung-Woong Kim
  12. Won-Jong Oh
(2024)
Repulsive Sema3E-Plexin-D1 signaling coordinates both axonal extension and steering via activating an autoregulatory factor, Mtss1
eLife 13:e96891.
https://doi.org/10.7554/eLife.96891

Share this article

https://doi.org/10.7554/eLife.96891

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