title: Small molecule screening identifies targetable zebrafish pigmentation pathways.
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.
authors.affiliation: Developmental Biology Programme, Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Colanesi
authors.forename: Kerrie L
authors.initials: KL
authors.lastname: Taylor
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Temperley
authors.forename: Pia R
authors.initials: PR
authors.lastname: Lundegaard
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.forename: Trista E
authors.initials: TE
authors.lastname: North
authors.forename: Hironori
authors.initials: H
authors.lastname: Ishizaki
authors.forename: Robert N
authors.initials: RN
authors.lastname: Kelsh
authors.forename: E Elizabeth
authors.initials: EE
authors.lastname: Patton
mesh_terms: D000818:Animals; D002452:Cell Count; D002856:Chromatophores / Q000166:cytology / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects; D053858:Metabolic Networks and Pathways / Q000187:drug effects*; D010641:Phenotype; D010858:Pigmentation / Q000187:drug effects*; D011687:Purines / Q000494:pharmacology; D011744:Pyrimidinones / Q000494:pharmacology; D000077546:Roscovitine; D054852:Small Molecule Libraries / Q000032:analysis* / Q000494:pharmacology*; D020032:Tyrphostins / Q000494:pharmacology; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism*
chemical_list: D016861:Cyclooxygenase Inhibitors; D006575:Heterocyclic Compounds, 3-Ring; D011687:Purines; D011744:Pyrimidinones; D054852:Small Molecule Libraries; D020032:Tyrphostins; D000077546:Roscovitine; C106250:6,7-dimethoxy-3-phenylquinoxaline; C447622:fiduxosin