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 PMID:29979149  

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

Jason J Early | Katy Lh Cole | Jill M Williamson | Matthew Swire | Hari Kamadurai | Marc Muskavitch | David A Lyons
eLife | 2018

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.

Pubmed ID: 29979149

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: Wellcome Trust, United Kingdom
  • Agency: Wellcome Trust, United Kingdom
    Id: 102836/Z/13/Z
  • Agency: Biotechnology and Biological Sciences Research Council, United Kingdom

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This is a list of tools and resources that we have found mentioned in this publication.


ImageJ (tool)

RRID:SCR_003070

Open source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.

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Vector Alignment Search Tool (tool)

RRID:SCR_010655

VAST is a computer algorithm developed at NCBI and used to identify similar protein 3-dimensional structures by purely geometric criteria, and to identify distant homologs that cannot be recognized by sequence comparison. Related structures for every structure in MMDB are pre-computed using VAST and accessible via links on the MMDB Structure Summary pages. The VAST Search page also allows you to compare the coordinates of a newly resolved structure in PDB format against all structures in MMDB to find its neighbors. Protein structure neighbors in Entrez are determined by direct comparison of 3-dimensional protein structures with the VAST algorithm. Each of the more than 87,804 domains in MMDB is compared to every other one. From the MMDB Structure summary pages, retrieved via Entrez, structure neighbors are available for protein chains and individual structural domains. If you already know a PDB/MMDB-Id you can try this at once, using the input form in the right column. VAST Search is a service that allows searching for structural neighbors starting with a set of 3D-coordinates specified by the user. This service is meant to be used with newly determined protein structures that are not yet part of MMDB. Structure neighbors for proteins already in MMDB have been pre-computed and can simply be looked up from MMDB''s Structure summary pages!

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Fiji (tool)

RRID:SCR_002285

Software package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.

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Adobe Photoshop (tool)

RRID:SCR_014199

Software for image processing, analysis, and editing. The software includes features such as touch capabilities, a customizable toolbar, 2D and 3D image merging, and Cloud access and options.

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B6;FVB-Tg(Olig2-EGFP/Rpl10a)JD97Htz/J (tool)

RRID:IMSR_JAX:030265

Mus musculus with name B6;FVB-Tg(Olig2-EGFP/Rpl10a)JD97Htz/J from IMSR.

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SD (tool)

RRID:RGD_70508

Rattus norvegicus with name SD from RGD.

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