Figure 1

Phenotype based chemical screening in zebrafish. Male and female pairs are bred to produce hundreds of single cell embryos that are fertilized ex vivo. For high throughput screening, groups of males and females can be bred within in a larger tank (group breeding), producing high numbers of embryos for screening. Breeding is synchronized by the light/dark cycles, and the fish tend to breed within the first two hours of light in the morning. In this example, embryos are arrayed in 96-well plates, each with a different chemical compound, and observed for a specific phenotype. The chemical in well A2 causes a loss of melanocytes, like MoTP [18]. MoTP can specifically kill differentiated melanocytes, and has become a valuable chemical tool to explore melanocyte stem cell biology [42–44]. Other small molecule screens in zebrafish have also identified pigmentation phenotypes [85, 86, 96]. In another example of a small molecule screen, compounds are screened for inhibition of tail fin regeneration. The tail fin is clipped and grows back within a few days. A zebrafish embryo treated with the compound from well B3, a glucocorticoid, does not correctly regenerate its tail fin [97].