PUBLICATION

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

Authors
Early, J.J., Cole, K.L., Williamson, J.M., Swire, M., Kamadurai, H., Muskavitch, M., Lyons, D.A.
ID
ZDB-PUB-180707-4
Date
2018
Source
eLIFE   7: (Journal)
Registered Authors
Cole, Katy, Lyons, David A., Williamson, Jill
Keywords
neuroscience, zebrafish
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Automation
  • Cell Count
  • Fluorescence
  • Genetic Testing*
  • High-Throughput Screening Assays
  • Image Processing, Computer-Assisted
  • Larva/metabolism
  • Myelin Sheath/metabolism*
  • Naphthalenes/pharmacology
  • Oligodendroglia/cytology
  • Pyrones/pharmacology
  • Reproducibility of Results
  • Spinal Cord/metabolism
  • Time-Lapse Imaging
  • Zebrafish/genetics*
PubMed
29979149 Full text @ Elife
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping