Fig. 5

(A) Schematic of zebrafish embryos injected with Tg (fli1a:GFP) at the 1-cell stage generate zebrafish larvae that are mosaic for the transgene integration and expression. (B) Image of mosaic expression of Tg (fli1a:GFP) in a vessel. (C) Images of zebrafish expressing WT or mutant BRAF^V600E in a mosaic fashion from a fli1a promoter in endothelial cells. Accumulation of blood is visible at the caudal vein vascular plexus in the BRAF^V600E–expressing zebrafish and outlined with a dashed red line. (D) Quantification of VM phenotype in BRAF^WT-expressing (n = 511) and BRAF^V600E-expressing (n = 779) zebrafish. (E) BRAF^WT and BRAF^V600E mosaic expression in stable Tg (fli1a:GFP) larvae to visualize all vessels in the zebrafish in the VM lesion. Increased numbers of vascular channels and disorganized architecture of VM lesions are clearly detectable. (F) Schematic of VM treatment protocol and quantification of the percentage of VM BRAF^V600E zebrafish with improved blood flow following treatment with vemurafenib. VM BRAF^V600E zebrafish were randomized prior to DMSO (n = 31) or vemurafenib (n = 19) treatment and blind scored. (G) Images of zebrafish expressing MAPK2K1^Q58del in a mosaic fashion from a fli1a promoter in endothelial cells (n = 5/37). Zebrafish larvae in D were analyzed by an unpaired parametric t test with Welch’s correction and in F by a paired t test comparing matched pairs (before and after treatment). Data are shown as SEM. ***P < 0.001.