1. Developmental Biology
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N-cadherin-regulated FGFR ubiquitination and degradation control mammalian neocortical projection neuron migration

  1. Elif Kon
  2. Elisa Calvo-Jimenez
  3. Alexia Cossard
  4. Youn Na
  5. Jonathan A Cooper
  6. Yves Jossin  Is a corresponding author
  1. Université Catholique de Louvain, Belgium
  2. Fred Hutchinson Cancer Research Center, United States
Research Article
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Cite this article as: eLife 2019;8:e47673 doi: 10.7554/eLife.47673

Abstract

The functions of FGF receptors (FGFRs) in early development of the cerebral cortex are well established. Their functions in the migration of neocortical projection neurons, however, are unclear. We have found that FGFRs regulate multipolar neuron orientation and the morphological change into bipolar cells necessary to enter the cortical plate. Mechanistically, our results suggest that FGFRs are activated by N-Cadherin. N-Cadherin cell-autonomously binds FGFRs and inhibits FGFR K27- and K29-linked polyubiquitination and lysosomal degradation. Accordingly, FGFRs accumulate and stimulate prolonged Erk1/2 phosphorylation. Neurons inhibited for Erk1/2 are stalled in the multipolar zone. We found that Reelin, prevents FGFR degradation in an N-Cadherin-dependent manner and stimulates prolonged, FGFR-dependent, Erk1/2 phosphorylation. These findings reveal novel functions for FGFRs in cortical projection neuron migration, suggest a physiological role for FGFR and N-Cadherin interaction in vivo and identify Reelin as an extracellular upstream regulator and Erk1/2 as downstream effectors of FGFRs during neuron migration.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files

Article and author information

Author details

  1. Elif Kon

    Laboratory of Mammalian Development and Cell Biology, Institute of Neuroscience, Université Catholique de Louvain, Brussels, Belgium
    Competing interests
    No competing interests declared.
  2. Elisa Calvo-Jimenez

    Laboratory of Mammalian Development and Cell Biology, Institute of Neuroscience, Université Catholique de Louvain, Brussels, Belgium
    Competing interests
    No competing interests declared.
  3. Alexia Cossard

    Laboratory of Mammalian Development and Cell Biology, Institute of Neuroscience, Université Catholique de Louvain, Brussels, Belgium
    Competing interests
    No competing interests declared.
  4. Youn Na

    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    No competing interests declared.
  5. Jonathan A Cooper

    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    Jonathan A Cooper, Senior editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8626-7827
  6. Yves Jossin

    Laboratory of Mammalian Development and Cell Biology, Institute of Neuroscience, Université Catholique de Louvain, Brussels, Belgium
    For correspondence
    yves.jossin@uclouvain.be
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8466-7432

Funding

Fonds De La Recherche Scientifique - FNRS (J.0129.15)

  • Yves Jossin

Fonds De La Recherche Scientifique - FNRS (J.0179.16)

  • Yves Jossin

Fonds De La Recherche Scientifique - FNRS (T.0243.18)

  • Yves Jossin

Fonds pour la Formation à la Recherche dans l'Industrie et dans l'Agriculture

  • Elif Kon
  • Elisa Calvo-Jimenez
  • Alexia Cossard

National Institutes of Health (R01-NS080194)

  • Jonathan A Cooper

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

Ethics

Animal experimentation: CD1 mice were bred in standard conditions and animal procedures were carried out in accordance with European guidelines and approved by the animal ethics committee of the Université Catholique de Louvain under the protocol number: 2017/UCL/MD/009.

Reviewing Editor

  1. Marianne E Bronner, California Institute of Technology, United States

Publication history

  1. Received: April 13, 2019
  2. Accepted: October 1, 2019
  3. Accepted Manuscript published: October 2, 2019 (version 1)
  4. Version of Record published: October 10, 2019 (version 2)

Copyright

© 2019, Kon 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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