An automated high-resolution in vivo screen in zebrafish to identify chemical regulators of myelination

  1. Jason J Early
  2. Katy LH Cole
  3. Jill M Williamson
  4. Matthew Swire
  5. Hari Kamadurai
  6. Marc Muskavitch
  7. David A Lyons  Is a corresponding author
  1. University of Edinburgh, United Kingdom
  2. Biogen, United States

Abstract

Myelinating oligodendrocytes are essential for central nervous system (CNS) formation and function. Their disruption is implicated in numerous neurodevelopmental, neuropsychiatric and neurodegenerative disorders. However, recent studies have indicated that oligodendrocytes may be tractable for treatment of disease. In recent years, zebrafish have become well established for the study of myelinating oligodendrocyte biology and drug discovery in vivo. Here, by automating the delivery of zebrafish larvae to a spinning disk confocal microscope, we were able to automate high-resolution imaging of myelinating oligodendrocytes in vivo. From there, we developed an image analysis pipeline that facilitated a screen of compounds with epigenetic and post-translational targets for their effects on regulating myelinating oligodendrocyte number. This screen identified novel compounds that strongly promote myelinating oligodendrocyte formation in vivo. Our imaging platform and analysis pipeline is flexible and can be employed for high-resolution imaging-based screens of broad interest using zebrafish.

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. Jason J Early

    Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4313-6445
  2. Katy LH Cole

    Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    Katy LH Cole, was funded by a collaborative grant from Biogen for part of the period of this project.
  3. Jill M Williamson

    Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    Jill M Williamson, was funded by a collaborative grant from Biogen for part of the period of this project.
  4. Matthew Swire

    Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    No competing interests declared.
  5. Hari Kamadurai

    Cell and Gene Therapy, Biogen, Cambridge, United States
    Competing interests
    No competing interests declared.
  6. Marc Muskavitch

    Cell and Gene Therapy, Biogen, Cambridge, United States
    Competing interests
    No competing interests declared.
  7. David A Lyons

    Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
    For correspondence
    david.lyons@ed.ac.uk
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1166-4454

Funding

Wellcome (102836/Z/13/Z)

  • David A Lyons

Lister Institute of Preventive Medicine

  • David A Lyons

Biogen

  • David A Lyons

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

Reviewing Editor

  1. Tanya T. Whitfield, University of Sheffield, United Kingdom

Ethics

Animal experimentation: All animal studies were carried out with approval from the UK Home Office and according to its regulations, under project licenses 60/ 8436 and 70/8436. The project was approved by the University of Edinburgh Institutional Animal Care and Use Committee.

Version history

  1. Received: January 16, 2018
  2. Accepted: July 5, 2018
  3. Accepted Manuscript published: July 6, 2018 (version 1)
  4. Version of Record published: July 23, 2018 (version 2)

Copyright

© 2018, Early 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. Jason J Early
  2. Katy LH Cole
  3. Jill M Williamson
  4. Matthew Swire
  5. Hari Kamadurai
  6. Marc Muskavitch
  7. David A Lyons
(2018)
An automated high-resolution in vivo screen in zebrafish to identify chemical regulators of myelination
eLife 7:e35136.
https://doi.org/10.7554/eLife.35136

Share this article

https://doi.org/10.7554/eLife.35136

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