An automated high-resolution in vivo screen in zebrafish to identify chemical regulators of myelination
- University of Edinburgh, United Kingdom
- 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.
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Author details
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.
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.
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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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
