Small molecule screening identifies targetable zebrafish pigmentation pathways

Sarah Colanesi, Kerrie L Taylor, Nicholas D Temperley, Pia R Lundegaard, Dong Liu, Trista E North, Hironori Ishizaki, Robert N Kelsh, E Elizabeth Patton

43 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalPigment Cell & Melanoma Research
Volume25
Issue number2
Pages (from-to)131-43
Number of pages13
ISSN1755-1471
DOIs
Publication statusPublished - Mar 2012

Keywords

  • Animals
  • Cell Count
  • Chromatophores
  • Cyclooxygenase Inhibitors
  • Drug Evaluation, Preclinical
  • Embryo, Nonmammalian
  • Heterocyclic Compounds, 3-Ring
  • Melanocytes
  • Metabolic Networks and Pathways
  • Phenotype
  • Pigmentation
  • Purines
  • Pyrimidinones
  • Small Molecule Libraries
  • Tyrphostins
  • Zebrafish

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