Figure 3.

Phenotypic screening of selected hits from MMV400 library for reduced cell motility phenotypes in zebrafish embryonic developmental assays. (A) Ezrin morphant embryos are shown at the time that wild-type siblings have reached the 60% epiboly stage (a). Arrows mark the location of marginal regions in wild-type embryos at 60% epiboly. Embryos were injected at the single cell stage with 3.3 ng ezrin MO (b), 6.6 ng ezrin MO (c), or 9.9 ng ezrin MO (d). Ezrin MO injections result in retarded epiboly, a thickened blastoderm, and defective involution of the blastoderm. (B) Small molecule treated embryos were scored for epiboly defects at early stages of development between 7.0 and 8.5 hpf. Embryos treated with small molecule inhibitor of ezrin, NSC305787, completely mimicked ezrin-MO-injected embryos. Treatment of the embryos with MMV Malaria Box compounds MMV020549 and MMV667492 resulted in delay of the epiboly progression around the yolk with increasing concentration of drugs compared to vehicle treated group. (C) Representative images of embryos treated with NSC305787 and MMV Malaria Box compounds MMV020549 and MMV667492 from Panel B are presented with different degrees of epiboly defects, compared to vehicle-treated controls, observed between 7.0 and 8.5 hpf.