Small molecule screening identifies targetable zebrafish pigmentation pathways

TY - JOUR

T1 - Small molecule screening identifies targetable zebrafish pigmentation pathways

AU - Colanesi, Sarah

AU - Taylor, Kerrie L

AU - Temperley, Nicholas D

AU - Lundegaard, Pia R

AU - Liu, Dong

AU - North, Trista E

AU - Ishizaki, Hironori

AU - Kelsh, Robert N

AU - Patton, E Elizabeth

N1 - © 2012 John Wiley & Sons A/S.

PY - 2012/3

Y1 - 2012/3

N2 - 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.

AB - 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.

KW - Animals

KW - Cell Count

KW - Chromatophores

KW - Cyclooxygenase Inhibitors

KW - Drug Evaluation, Preclinical

KW - Embryo, Nonmammalian

KW - Heterocyclic Compounds, 3-Ring

KW - Melanocytes

KW - Metabolic Networks and Pathways

KW - Phenotype

KW - Pigmentation

KW - Purines

KW - Pyrimidinones

KW - Small Molecule Libraries

KW - Tyrphostins

KW - Zebrafish

U2 - 10.1111/j.1755-148x.2012.00977.x

DO - 10.1111/j.1755-148x.2012.00977.x

M3 - Journal article

C2 - 22252091

SN - 1755-1471

VL - 25

SP - 131

EP - 143

JO - Pigment Cell & Melanoma Research

JF - Pigment Cell & Melanoma Research

IS - 2

ER -