Small molecule-induced ablation and subsequent regeneration of larval zebrafish melanocytes.
We developed a method to efficiently ablate a single cell type, the zebrafish melanocyte, and study the mechanisms of its regeneration. We found that a small molecule, (2-morpholinobutyl)-4-thiophenol (MoTP), specifically ablates zebrafish larval melanocytes or melanoblasts, and that this melanocytotoxicity is dependent on tyrosinase activity, which presumably converts MoTP to cytotoxic quinone species. Following melanocyte ablation by MoTP treatment, we demonstrate by BrdU incorporation experiments that regenerated melanocytes are derived from the division of otherwise quiescent melanocyte precursors or stem cells. We further show that larval melanocyte regeneration requires the kit receptor tyrosine kinase. Our results suggest that a small number of melanocyte precursors or stem cells unevenly distributed in larvae are drawn upon to reconstitute the larval melanocyte population following melanocyte ablation by MoTP.
Yang
Chao-Tsung
CT
Department of Genetics, Washington University School of Medicine, 4566 Scott Avenue, Saint Louis, MO 63110, USA.
Johnson
Stephen L
SL
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D017403:In Situ Hybridization / Q000379:methods; D007814:Larva / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000378:metabolism; D009025:Morpholines / Q000737:chemistry / Q000494:pharmacology*; D009154:Mutation / Q000235:genetics; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000633:toxicity*; D015027:Zebrafish / Q000235:genetics* / Q000378:metabolism
C515849:(2-morpholinobutyl)-4-thiophenol; D009025:Morpholines; D010636:Phenols; D013438:Sulfhydryl Compounds; C042983:thiophenol; D014442:Monophenol Monooxygenase