Small molecule screening identifies targetable zebrafish pigmentation pathways

被引：58

作者：

Colanesi, Sarah ^{[1
]}

Taylor, Kerrie L. ^{[2
,3
]}

Temperley, Nicholas D. ^{[2
,3
]}

Lundegaard, Pia R. ^{[2
,3
,4
]}

Liu, Dong ^{[2
,3
]}

North, Trista E. ^{[5
]}

Ishizaki, Hironori ^{[2
,3
]}

Kelsh, Robert N. ^{[1
]}

Patton, E. Elizabeth ^{[2
,3
]}

机构：

[1] Univ Bath, Dept Biol & Biochem, Ctr Regenerat Med, Dev Biol Programme, Bath BA2 7AY, Avon, England

[2] Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland

[3] Univ Edinburgh, Edinburgh Canc Res UK Ctr, Edinburgh, Midlothian, Scotland

[4] NeuroSearch AS, Ballerup, Denmark

[5] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA

来源：

PIGMENT CELL & MELANOMA RESEARCH | 2012年 / 25卷 / 02期

基金：

英国生物技术与生命科学研究理事会; 英国医学研究理事会;

关键词：

pigment cell; melanocyte; iridophore; small molecule; development; screen; zebrafish; FRESH-WATER GOBY; NEURAL-CREST; MELANOSOME DISPERSION; ODONTOBUTIS-OBSCURA; SKIN PIGMENTATION; HUMAN MELANOCYTES; CELL-DEVELOPMENT; MOTILE ACTIVITY; REGENERATION; MUTATIONS;

D O I：

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

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：131 / 143

页数：14

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