1. Developmental Biology
  2. Neuroscience
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CRMP4-mediated fornix development involves semaphorin-3E signaling pathway

  1. Benoît Boulan
  2. Charlotte Ravanello
  3. Amandine Peyrel
  4. Christophe Bosc
  5. Christian Delphin
  6. Florence Appaix
  7. Eric Denarier
  8. Alexandra Kraut
  9. Muriel Jacquier-Sarlin
  10. Alyson Fournier
  11. Annie Andrieux
  12. Sylvie Gory-Fauré  Is a corresponding author
  13. Jean-Christophe Deloulme  Is a corresponding author
  1. Univ. Grenoble Alpes, Inserm, U1216, CEA, Grenoble Institut Neurosciences, France
  2. Univ. Grenoble Alpes, INSERM, CEA, UMR BioSanté U1292, CNRS, CEA, France
  3. McGill University, Canada
Research Article
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Cite this article as: eLife 2021;10:e70361 doi: 10.7554/eLife.70361

Abstract

Neurodevelopmental axonal pathfinding plays a central role in correct brain wiring and subsequent cognitive abilities. Within the growth cone, various intracellular effectors transduce axonal guidance signals by remodeling the cytoskeleton. Semaphorin-3E (Sema3E) is a guidance cue implicated in development of the fornix, a neuronal tract connecting the hippocampus to the hypothalamus. Microtubule-Associated Protein 6 (MAP6) has been shown to be involved in the Sema3E growth-promoting signaling pathway. In this study, we identified the Collapsin Response Mediator Protein 4 (CRMP4) as a MAP6 partner and a crucial effector in Sema3E growth-promoting activity. CRMP4-KO mice displayed abnormal fornix development reminiscent of that observed in Sema3E-KO mice. CRMP4 was shown to interact with the Sema3E tripartite receptor complex within Detergent-Resistant Membrane (DRM) domains, and DRM domain integrity was required to transduce Sema3E signaling through the Akt/GSK3 pathway. Finally, we showed that the cytoskeleton-binding domain of CRMP4 is required for Sema3E's growth-promoting activity, suggesting that CRMP4 plays a role at the interface between Sema3E receptors, located in DRM domains, and the cytoskeleton network. As the fornix is affected in many psychiatric diseases, such as schizophrenia, our results provide new insights to better understand the neurodevelopmental components of these diseases.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figure 2, Figure 4, Figure 5, Figure 6 , Figure 7, Figure 8, Figure 9, Figure 10 and supplementary File 1

Article and author information

Author details

  1. Benoît Boulan

    Univ. Grenoble Alpes, Inserm, U1216, CEA, Grenoble Institut Neurosciences, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6793-5378
  2. Charlotte Ravanello

    Univ. Grenoble Alpes, Inserm, U1216, CEA, Grenoble Institut Neurosciences, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Amandine Peyrel

    Univ. Grenoble Alpes, Inserm, U1216, CEA, Grenoble Institut Neurosciences, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Christophe Bosc

    Univ. Grenoble Alpes, Inserm, U1216, CEA, Grenoble Institut Neurosciences, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Christian Delphin

    Univ. Grenoble Alpes, Inserm, U1216, CEA, Grenoble Institut Neurosciences, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Florence Appaix

    Univ. Grenoble Alpes, Inserm, U1216, CEA, Grenoble Institut Neurosciences, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Eric Denarier

    Univ. Grenoble Alpes, Inserm, U1216, CEA, Grenoble Institut Neurosciences, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4169-397X
  8. Alexandra Kraut

    Univ. Grenoble Alpes, INSERM, CEA, UMR BioSanté U1292, CNRS, CEA, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
  9. Muriel Jacquier-Sarlin

    Univ. Grenoble Alpes, Inserm, U1216, CEA, Grenoble Institut Neurosciences, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8501-7511
  10. Alyson Fournier

    Department of Neurology and Neurosurgery, Montréal Neurological Institute, McGill University, Montréal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  11. Annie Andrieux

    Univ. Grenoble Alpes, Inserm, U1216, CEA, Grenoble Institut Neurosciences, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4022-6405
  12. Sylvie Gory-Fauré

    Univ. Grenoble Alpes, Inserm, U1216, CEA, Grenoble Institut Neurosciences, Grenoble, France
    For correspondence
    sylvie.gory-faure@univ-grenoble-alpes.fr
    Competing interests
    The authors declare that no competing interests exist.
  13. Jean-Christophe Deloulme

    Univ. Grenoble Alpes, Inserm, U1216, CEA, Grenoble Institut Neurosciences, Grenoble, France
    For correspondence
    Jean-Christophe.deloulme@univ-grenoble-alpes.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2234-5865

Funding

Agence Nationale de la Recherche (2010- Blanc-120201 CBioS)

  • Christophe Bosc

Agence Nationale de la Recherche (2017-CE11-0026 MAMAs)

  • Annie Andrieux

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

Ethics

Animal experimentation: The study protocol was approved by the local animal welfare committee (Comité Local GIN, C2EA-04 - APAFIS number 8303-2016060110523424) and complied with EU guidelines (directive 2010/63/EU). Every precaution was taken to minimize the number of animals used and stress to animals during experiments.

Reviewing Editor

  1. Fadel Tissir, Université Catholique de Louvain, Belgium

Publication history

  1. Received: May 14, 2021
  2. Accepted: December 2, 2021
  3. Accepted Manuscript published: December 3, 2021 (version 1)
  4. Accepted Manuscript updated: December 6, 2021 (version 2)
  5. Accepted Manuscript updated: December 6, 2021 (version 3)
  6. Accepted Manuscript updated: December 13, 2021 (version 4)
  7. Version of Record published: December 17, 2021 (version 5)
  8. Version of Record updated: December 20, 2021 (version 6)

Copyright

© 2021, Boulan 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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