1. Developmental Biology
  2. Neuroscience
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Cadherins regulate nuclear topography and function of developing ocular motor circuitry

  1. Athene Knüfer
  2. Giovanni Diana
  3. Gregory S Walsh
  4. Jonathan DW Clarke  Is a corresponding author
  5. Sarah Guthrie  Is a corresponding author
  1. King's College London, United Kingdom
  2. Virginia Commonwealth University, United States
  3. University of Sussex, United Kingdom
Research Article
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Cite this article as: eLife 2020;9:e56725 doi: 10.7554/eLife.56725

Abstract

In the vertebrate central nervous system, groups of functionally-related neurons, including cranial motor neurons of the brainstem, are frequently organised as nuclei. The molecular mechanisms governing the emergence of nuclear topography and circuit function are poorly understood. Here we investigate the role of cadherin-mediated adhesion in the development of zebrafish ocular motor (sub)nuclei. We find that developing ocular motor (sub)nuclei differentially express classical cadherins. Perturbing cadherin function in these neurons results in distinct defects in neuronal positioning, including scattering of dorsal cells and defective contralateral migration of ventral subnuclei. In addition, we show that cadherin-mediated interactions between adjacent subnuclei are critical for subnucleus position. We also find that disrupting cadherin adhesivity in dorsal oculomotor neurons impairs the larval optokinetic reflex, suggesting that neuronal clustering is important for co-ordinating circuit function. Our findings reveal that cadherins regulate distinct aspects of cranial motor neuron positioning and establish subnuclear topography and motor function.

Article and author information

Author details

  1. Athene Knüfer

    Centre for Developmental Neurobiology, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Giovanni Diana

    Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7497-5271
  3. Gregory S Walsh

    Department of Biology, Virginia Commonwealth University, Richmond, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Jonathan DW Clarke

    Department of Developmental Neurobiology, King's College London, London, United Kingdom
    For correspondence
    jon.clarke@kcl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
  5. Sarah Guthrie

    Sussex Neuroscience, School of Life Sciences, University of Sussex, Brighton, United Kingdom
    For correspondence
    S.Guthrie@sussex.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8446-9150

Funding

Biotechnology and Biological Sciences Research Council (BB/J014567/1)

  • Athene Knüfer

Company of Biologists (DEV-170218)

  • Athene Knüfer

Wellcome Trust (102895/Z/13/Z)

  • Jonathan DW Clarke

Medical Research Council (MR/L020742/2)

  • Sarah Guthrie

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

Ethics

Animal experimentation: This work was approved by the local Animal Care and Use Committee (King's College London) and was carried out in accordance with the Animals (Experimental Procedures) Act, 1986, under licence from the United Kingdom Home Office (PPLs: 70/7753 and P70880F4C-Z001, PIL: I1D87502D).

Reviewing Editor

  1. Marianne E Bronner, California Institute of Technology, United States

Publication history

  1. Received: March 7, 2020
  2. Accepted: September 30, 2020
  3. Accepted Manuscript published: October 1, 2020 (version 1)
  4. Version of Record published: October 30, 2020 (version 2)

Copyright

© 2020, Knüfer 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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