Abstract

Cell migration is a dynamic process that entails extensive protein synthesis and recycling, structural remodeling, and considerable bioenergetic demand. Autophagy is one of the pathways that maintain cellular homeostasis. Time-lapse imaging of autophagosomes and ATP/ADP levels in migrating cells in the rostral migratory stream of mice revealed that decreases in ATP levels force cells into the stationary phase and induce autophagy. Pharmacological or genetic impairments of autophagy in neuroblasts using either bafilomycin, inducible conditional mice, or CRISPR/Cas9 gene editing decreased cell migration due to the longer duration of the stationary phase. Autophagy is modulated in response to migration-promoting and inhibiting molecular cues and is required for the recycling of focal adhesions. Our results show that autophagy and energy consumption act in concert in migrating cells to dynamically regulate the pace and periodicity of the migratory and stationary phases in order to sustain neuronal migration.

Data availability

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

Article and author information

Author details

  1. Cedric Bressan

    CERVO Brain Research Center, Université Laval, Quebec, Canada
    Competing interests
    The authors declare that no competing interests exist.
  2. Alessandra Pecora

    CERVO Brain Research Center, Université Laval, Quebec, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Dave Gagnon

    Psychiatry and Neuroscience, Université Laval, Quebec, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7366-0665
  4. Marina Snapyan

    CERVO Brain Research Center, Université Laval, Quebec, Canada
    Competing interests
    The authors declare that no competing interests exist.
  5. Simon Labrecque

    CERVO Brain Research Center, Université Laval, Quebec, Canada
    Competing interests
    The authors declare that no competing interests exist.
  6. Paul De Koninck

    Biochimie, Microbiologie & Bio-inormatique, Université Laval, Quebec, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6436-1062
  7. Martin Parent

    Psychiatry and neuroscience, Université Laval, Quebec City, Canada
    Competing interests
    The authors declare that no competing interests exist.
  8. Armen Saghatelyan

    Psychiatry and Neuroscience, Université Laval, Quebec, Canada
    For correspondence
    armen.saghatelyan@fmed.ulaval.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4962-0465

Funding

Canadian Institutes of Health Research (PJT 153026)

  • Armen Saghatelyan

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

Reviewing Editor

  1. D Nora Abrous, Neurocentre Magendie, INSERM, France

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations of Canadian Council of Animal Care. All the experiments were approved by the Université Laval animal protection committee (#2014-178 and 2019-020).

Version history

  1. Received: February 13, 2020
  2. Accepted: September 26, 2020
  3. Accepted Manuscript published: September 28, 2020 (version 1)
  4. Version of Record published: October 14, 2020 (version 2)

Copyright

© 2020, Bressan 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.

Metrics

  • 2,753
    views
  • 332
    downloads
  • 22
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Cedric Bressan
  2. Alessandra Pecora
  3. Dave Gagnon
  4. Marina Snapyan
  5. Simon Labrecque
  6. Paul De Koninck
  7. Martin Parent
  8. Armen Saghatelyan
(2020)
The dynamic interplay between ATP/ADP levels and autophagy sustain neuronal migration in vivo
eLife 9:e56006.
https://doi.org/10.7554/eLife.56006

Share this article

https://doi.org/10.7554/eLife.56006

Further reading

    1. Neuroscience
    Annette Pisanski, Mitchell Prostebby ... Silvia Pagliardini
    Research Article

    The lateral parafacial area (pFL) is a crucial region involved in respiratory control, particularly in generating active expiration through an expiratory oscillatory network. Active expiration involves rhythmic abdominal (ABD) muscle contractions during late-expiration, increasing ventilation during elevated respiratory demands. The precise anatomical location of the expiratory oscillator within the ventral medulla’s rostro-caudal axis is debated. While some studies point to the caudal tip of the facial nucleus (VIIc) as the oscillator’s core, others suggest more rostral areas. Our study employed bicuculline (a γ-aminobutyric acid type A [GABA-A] receptor antagonist) injections at various pFL sites (–0.2 mm to +0.8 mm from VIIc) to investigate the impact of GABAergic disinhibition on respiration. These injections consistently elicited ABD recruitment, but the response strength varied along the rostro-caudal zone. Remarkably, the most robust and enduring changes in tidal volume, minute ventilation, and combined respiratory responses occurred at more rostral pFL locations (+0.6/+0.8 mm from VIIc). Multivariate analysis of the respiratory cycle further differentiated between locations, revealing the core site for active expiration generation with this experimental approach. Our study advances our understanding of neural mechanisms governing active expiration and emphasizes the significance of investigating the rostral pFL region.

    1. Neuroscience
    Max Schulz, Malte Wöstmann
    Insight

    Asymmetries in the size of structures deep below the cortex explain how alpha oscillations in the brain respond to shifts in attention.