Small molecule screening identifies targetable zebrafish pigmentation pathways

Authors

  • Sarah Colanesi,

    1. Developmental Biology Programme, Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath, UK
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  • Kerrie L. Taylor,

    1. Institute for Genetics and Molecular Medicine, MRC Human Genetics Unit and the Edinburgh Cancer Research UK Centre, The University of Edinburgh, Edinburgh, UK
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  • Nicholas D. Temperley,

    1. Institute for Genetics and Molecular Medicine, MRC Human Genetics Unit and the Edinburgh Cancer Research UK Centre, The University of Edinburgh, Edinburgh, UK
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  • Pia R. Lundegaard,

    1. Institute for Genetics and Molecular Medicine, MRC Human Genetics Unit and the Edinburgh Cancer Research UK Centre, The University of Edinburgh, Edinburgh, UK
    2. NeuroSearch A/S, Ballerup, Denmark
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  • Dong Liu,

    1. Institute for Genetics and Molecular Medicine, MRC Human Genetics Unit and the Edinburgh Cancer Research UK Centre, The University of Edinburgh, Edinburgh, UK
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  • Trista E. North,

    1. Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA
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  • Hironori Ishizaki,

    1. Institute for Genetics and Molecular Medicine, MRC Human Genetics Unit and the Edinburgh Cancer Research UK Centre, The University of Edinburgh, Edinburgh, UK
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  • Robert N. Kelsh,

    1. Developmental Biology Programme, Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath, UK
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  • E. Elizabeth Patton

    1. Institute for Genetics and Molecular Medicine, MRC Human Genetics Unit and the Edinburgh Cancer Research UK Centre, The University of Edinburgh, Edinburgh, UK
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Robert N. Kelsh, e-mail: bssrnk@bath.ac.uk
E. E. Patton, e-mail: e.patton@hgu.mrc.ac.uk

Summary

Small molecules complement genetic mutants and can be used to probe pigment cell biology by inhibiting specific proteins or pathways. Here, we present the results of a screen of active compounds for those that affect the processes of melanocyte and iridophore development in zebrafish and investigate the effects of a few of these compounds in further detail. We identified and confirmed 57 compounds that altered pigment cell patterning, number, survival, or differentiation. Additional tissue targets and toxicity of small molecules are also discussed. Given that the majority of cell types, including pigment cells, are conserved between zebrafish and other vertebrates, we present these chemicals as molecular tools to study developmental processes of pigment cells in living animals and emphasize the value of zebrafish as an in vivo system for testing the on- and off-target activities of clinically active drugs.

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