1. Neuroscience
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Formation of retinal direction-selective circuitry initiated by starburst amacrine cell homotypic contact

  1. Thomas A Ray
  2. Suva Roy
  3. Christopher Kozlowski
  4. Jingjing Wang
  5. Jon Cafaro
  6. Samuel W Hulbert
  7. Christopher V E Wright
  8. Greg D Field
  9. Jeremy N Kay  Is a corresponding author
  1. Duke University School of Medicine, United States
  2. Vanderbilt University School of Medicine, United States
Research Article
  • Cited 15
  • Views 2,787
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Cite this article as: eLife 2018;7:e34241 doi: 10.7554/eLife.34241

Abstract

A common strategy by which developing neurons locate their synaptic partners is through projections to circuit-specific neuropil sublayers. Once established, sublayers serve as a substrate for selective synapse formation, but how sublayers arise during neurodevelopment remains unknown. Here we identify the earliest events that initiate formation of the direction-selective circuit in the inner plexiform layer of mouse retina. We demonstrate that radially-migrating newborn starburst amacrine cells establish homotypic contacts on arrival at the inner retina. These contacts, mediated by the cell-surface protein MEGF10, trigger neuropil innervation resulting in generation of two sublayers comprising starburst-cell dendrites. This dendritic scaffold then recruits projections from circuit partners. Abolishing MEGF10-mediated contacts profoundly delays and ultimately disrupts sublayer formation, leading to broader direction tuning and weaker direction-selectivity in retinal ganglion cells. Our findings reveal a mechanism by which differentiating neurons transition from migratory to mature morphology, and highlight this mechanism's importance in forming circuit-specific sublayers.

Article and author information

Author details

  1. Thomas A Ray

    Department of Neurobiology, Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Suva Roy

    Department of Neurobiology, Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Christopher Kozlowski

    Department of Neurobiology, Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Jingjing Wang

    Department of Neurobiology, Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Jon Cafaro

    Department of Neurobiology, Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Samuel W Hulbert

    Department of Neurobiology, Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0369-0150
  7. Christopher V E Wright

    Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9260-4009
  8. Greg D Field

    Department of Neurobiology, Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Jeremy N Kay

    Department of Neurobiology, Duke University School of Medicine, Durham, United States
    For correspondence
    jeremy.kay@duke.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6145-1604

Funding

National Eye Institute (EY024694)

  • Jeremy N Kay

National Eye Institute (EY5722 to Duke University)

  • Thomas A Ray
  • Suva Roy
  • Christopher Kozlowski
  • Jingjing Wang
  • Jon Cafaro
  • Samuel W Hulbert
  • Greg D Field
  • Jeremy N Kay

Pew Charitable Trusts

  • Jeremy N Kay

E. Matilda Ziegler Foundation for the Blind

  • Jeremy N Kay

McKnight Endowment Fund for Neuroscience

  • Jeremy N Kay

Alfred P. Sloan Foundation

  • Jeremy N Kay

Whitehall Foundation

  • Greg D Field

Research to Prevent Blindness (Unrestricted grant to Duke University)

  • Thomas A Ray
  • Suva Roy
  • Christopher Kozlowski
  • Jingjing Wang
  • Jon Cafaro
  • Greg D Field
  • Jeremy N Kay

National Eye Institute (EY026344)

  • Thomas A Ray

National Eye Institute (EY024567)

  • Greg D Field

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

Ethics

Animal experimentation: All animal experimental procedures were reviewed and approved by the Institutional Animal Care and Use Committee of Duke University (protocol A005-16-01).

Reviewing Editor

  1. Jeremy Nathans, Johns Hopkins University School of Medicine, United States

Publication history

  1. Received: December 11, 2017
  2. Accepted: March 29, 2018
  3. Accepted Manuscript published: April 3, 2018 (version 1)
  4. Version of Record published: May 2, 2018 (version 2)

Copyright

© 2018, Ray 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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