Repulsive Sema3E-Plexin-D1 signaling coordinates both axonal extension and steering via activating an autoregulatory factor, Mtss1
- Korea Brain Research Institute, Republic of Korea
- Korea Brain Research Institute, Korea (South), Republic of
- 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.
Article and author information
Author details
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.
Reviewing Editor
- Jun Ding, Stanford University, United States
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.
Version history
- Preprint posted: May 4, 2022 (view preprint)
- Received: February 7, 2024
- Accepted: March 14, 2024
- Accepted Manuscript published: March 25, 2024 (version 1)
- Version of Record published: April 8, 2024 (version 2)
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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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
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