Dystroglycan is a scaffold for extracellular axon guidance decisions

  1. L Bailey Lindenmaier
  2. Nicolas Parmentier
  3. Caiying Guo
  4. Fadel Tissir
  5. Kevin M Wright  Is a corresponding author
  1. Oregon Health and Science University, United States
  2. Universite' Catholique de Louvain, Belgium
  3. Janelia Research Campus, Howard Hughes Medical Institute, United States

Abstract

Axon guidance requires interactions between extracellular signaling molecules and transmembrane receptors, but how appropriate context-dependent decisions are coordinated outside the cell remains unclear. Here we show that the transmembrane glycoprotein Dystroglycan interacts with a changing set of environmental cues that regulate the trajectories of extending axons throughout the mammalian brain and spinal cord. Dystroglycan operates primarily as an extracellular scaffold during axon guidance, as it functions non-cell autonomously and does not require signaling through its intracellular domain. We identify the transmembrane receptor Celsr3/Adgrc3 as a binding partner for Dystroglycan, and show that this interaction is critical for specific axon guidance events in vivo. These findings establish Dystroglycan as a multifunctional scaffold that coordinates extracellular matrix proteins, secreted cues, and transmembrane receptors to regulate axon guidance.

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. L Bailey Lindenmaier

    Vollum Institute, Oregon Health and Science University, Portland, United States
    Competing interests
    No competing interests declared.
  2. Nicolas Parmentier

    Institute of Neuroscience, Universite' Catholique de Louvain, Brussels, Belgium
    Competing interests
    No competing interests declared.
  3. Caiying Guo

    Gene Targeting and Transgenics Resources, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    No competing interests declared.
  4. Fadel Tissir

    Institute of Neuroscience, Universite' Catholique de Louvain, Brussels, Belgium
    Competing interests
    Fadel Tissir, Reviewing editor, eLife.
  5. Kevin M Wright

    Vollum Institute, Oregon Health and Science University, Portland, United States
    For correspondence
    wrighke@ohsu.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5094-5270

Funding

National Institutes of Health (NS091027)

  • Kevin M Wright

Medical Research Foundation (N/A)

  • Kevin M Wright

ARC (17/22-079)

  • Fadel Tissir

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

Ethics

Animal experimentation: Mice were handled and bred in accordance with the Oregon Health and Science University IACUC guidelines, protocol #IP00000539.

Copyright

© 2019, Lindenmaier 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. L Bailey Lindenmaier
  2. Nicolas Parmentier
  3. Caiying Guo
  4. Fadel Tissir
  5. Kevin M Wright
(2019)
Dystroglycan is a scaffold for extracellular axon guidance decisions
eLife 8:e42143.
https://doi.org/10.7554/eLife.42143

Share this article

https://doi.org/10.7554/eLife.42143

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