Synergistic integration of Netrin and ephrin axon guidance signals by spinal motor neurons

  1. Sebastian Poliak
  2. Daniel Morales
  3. Louis-Philippe Croteau
  4. Dayana Krawchuk
  5. Elena Palmesino
  6. Susan Morton
  7. Cloutier Jean-François
  8. Frederic Charron
  9. Matthew B Dalva
  10. Susan L Ackerman
  11. Tzu-Jen Kao
  12. Artur Kania  Is a corresponding author
  1. Columbia University, United States
  2. Institut de recherches cliniques de Montreal, Canada
  3. Montreal Neurological Institute, Canada
  4. Department of Neuroscience, The Farber Institute for Neurosciences, Jefferson Hospital for Neuroscience, United States
  5. Howard Hughes Medical Institute, The Jackson Laboratory, United States
  6. Taipei Medical University, Taiwan

Abstract

During neural circuit assembly, axonal growth cones are exposed to multiple guidance signals at trajectory choice points. While axonal responses to individual guidance cues have been extensively studied, less is known about responses to combination of signals and underlying molecular mechanisms. Here, we studied the convergence of signals directing trajectory selection of spinal motor axons entering the limb. We first demonstrate that Netrin-1 attracts and repels distinct motor axon populations, according to their expression of Netrin receptors. Quantitative in vitro assays demonstrate that motor axons synergistically integrate both, attractive or repulsive Netrin-1 signals together with repulsive ephrin signals. Our investigations of the mechanism of ephrin-B2 and Netrin-1 integration demonstrate that the Netrin receptor Unc5c and the ephrin receptor EphB2 can form a complex in a ligand-dependent manner and that Netrin-ephrin synergistic growth cones responses involve the potentiation of Src family kinase signaling, a common effector of both pathways.

Article and author information

Author details

  1. Sebastian Poliak

    Department of Neuroscience, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Daniel Morales

    Neural Circuit Development Laboratory, Institut de recherches cliniques de Montreal, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Louis-Philippe Croteau

    Neural Circuit Development Laboratory, Institut de recherches cliniques de Montreal, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. Dayana Krawchuk

    Neural Circuit Development Laboratory, Institut de recherches cliniques de Montreal, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  5. Elena Palmesino

    Neural Circuit Development Laboratory, Institut de recherches cliniques de Montreal, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  6. Susan Morton

    Department of Neuroscience, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Cloutier Jean-François

    Montreal Neurological Institute, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  8. Frederic Charron

    Institut de recherches cliniques de Montreal, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  9. Matthew B Dalva

    Thomas Jefferson University, Department of Neuroscience, The Farber Institute for Neurosciences, Jefferson Hospital for Neuroscience, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Susan L Ackerman

    Howard Hughes Medical Institute, The Jackson Laboratory, Bar Harbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Tzu-Jen Kao

    Graduate Institute of Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
    Competing interests
    The authors declare that no competing interests exist.
  12. Artur Kania

    Neural Circuit Development Lab, Institut de recherches cliniques de Montreal, Montreal, Canada
    For correspondence
    artur.kania@ircm.qc.ca
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Graeme W Davis, University of California, San Francisco, United States

Ethics

Animal experimentation: All experimental procedures were approved by the Animal Care Committee at the Institut de Recherches Cliniques de Montréal, in accordance with the regulations of the Canadian Council on Animal Care. The following protocol reference numbers were used: 2005-03, 2008-18, 2009-10, 2011-30 and 2012-22.

Version history

  1. Received: August 13, 2015
  2. Accepted: December 2, 2015
  3. Accepted Manuscript published: December 3, 2015 (version 1)
  4. Version of Record published: February 12, 2016 (version 2)

Copyright

© 2015, Poliak 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. Sebastian Poliak
  2. Daniel Morales
  3. Louis-Philippe Croteau
  4. Dayana Krawchuk
  5. Elena Palmesino
  6. Susan Morton
  7. Cloutier Jean-François
  8. Frederic Charron
  9. Matthew B Dalva
  10. Susan L Ackerman
  11. Tzu-Jen Kao
  12. Artur Kania
(2015)
Synergistic integration of Netrin and ephrin axon guidance signals by spinal motor neurons
eLife 4:e10841.
https://doi.org/10.7554/eLife.10841

Share this article

https://doi.org/10.7554/eLife.10841

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