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LKB1 coordinates neurite remodeling to drive synapse layer emergence in the outer retina

  1. Courtney A Burger
  2. Jonathan Alevy
  3. Anna K Casasent
  4. Danye Jiang
  5. Nicholas E Albrecht
  6. Justine H Liang
  7. Arlene A Hirano
  8. Nicholas Brecha
  9. Melanie A Samuel  Is a corresponding author
  1. Baylor College of Medicine, United States
  2. David Geffen School of Medicine, University of California, Los Angeles, United States
Research Article
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Cite this article as: eLife 2020;9:e56931 doi: 10.7554/eLife.56931

Abstract

Structural changes in pre and postsynaptic neurons that accompany synapse formation often temporally and spatially overlap. Thus, it has been difficult to resolve which processes drive patterned connectivity. To overcome this, we use the laminated outer murine retina. We identify the serine/threonine kinase LKB1 as a key driver of synapse layer emergence. The absence of LKB1 in the retina caused a marked mislocalization and delay in synapse layer formation. In parallel, LKB1 modulated postsynaptic horizontal cell refinement and presynaptic photoreceptor axon growth. Mislocalized horizontal cell processes contacted aberrant cone axons in LKB1 mutants. These defects coincided with altered synapse protein organization, and horizontal cell neurites were misdirected to ectopic synapse protein regions. Together, these data suggest that LKB1 instructs the timing and location of connectivity in the outer retina via coordinate regulation of pre and postsynaptic neuron structure and the localization of synapse-associated proteins.

Article and author information

Author details

  1. Courtney A Burger

    Department of Neuroscience, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Jonathan Alevy

    Department of Neuroscience, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Anna K Casasent

    Department of Neuroscience, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Danye Jiang

    Department of Neuroscience, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Nicholas E Albrecht

    Department of Neurosciencew, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Justine H Liang

    Department of Neuroscience, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Arlene A Hirano

    Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8842-3582
  8. Nicholas Brecha

    Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Melanie A Samuel

    Department of Neuroscience, Baylor College of Medicine, Houston, United States
    For correspondence
    msamuel@bcm.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4804-2491

Funding

National Institute on Aging (1R56AG061808-01)

  • Melanie A Samuel

National Eye Institute (R01 EY030458-01)

  • Melanie A Samuel

Ted Nash Foundation

  • Melanie A Samuel

Brain Reserach Foundation

  • Melanie A Samuel

National Eye Institute (DP2EY027984-02)

  • Melanie A Samuel

National Eye Institute (T32EY007001)

  • Courtney A Burger

National Institute of General Medical Sciences (T32GM088129)

  • Nicholas E Albrecht

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

Ethics

Animal experimentation: Experiments were carried out in male and female mice in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the NIH under protocols approved by the BCM Institutional Animal Care and Use Committee (AN6785). Every effort was made to minimize animal suffering.

Reviewing Editor

  1. Gary L Westbrook, Oregon Health and Science University, United States

Publication history

  1. Received: March 25, 2020
  2. Accepted: April 11, 2020
  3. Accepted Manuscript published: May 7, 2020 (version 1)
  4. Version of Record published: May 19, 2020 (version 2)

Copyright

© 2020, Burger 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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