We raised all the transplanted fish and we observed that 57% of nacre fish receiving cells from kita-GFP-RAS donors developed tumors associated with a black caudal fin phenotype. In AB hosts, donor kita-GFP-RAS cells survived and proliferate to generate melanocytic hyperplasia in a similar percentage of cases. This result suggests that kita-GFPRAS cells maintain their transformed and aggressive phenotype in a completely cell-autonomous fashion, and that ras-expressing melanocytes survive and thrive equally well in the presence or in the absence of competition from host melanocytes. Thus, a large percentage of kita-GFP-RAS expressing cells is able to initiate melanoma development in a host environment. Altogether, these results suggest that targeting the expression of the HRAS MK-1775 oncogene to a population of cells that express the kita gene is able to induce melanoma development with high efficiency and in a relatively short time. We hypothesize that the aggressive features of our model depends not so much on the oncogene which has been used also in another zebrafish model of melanoma, but rather on the cell types that are targeted by the kita promoter perhaps also in conjunction with higher levels of oncogene expression. We tested the ability of the UAS:HRASV12 transgene to induce melanoma development following expression in somatic cells line – named mitfa:Gal4 to simplify, or in the kita:Gal4 line, figure 7a). This approach is commonly thought to yield high level of expression. Here we evaluated abnormal melanocyte proliferation at 4dpf, 15dpf and transformation at 1 month in larvae/juveniles that were selected for 1 or more transient integration events at 2 dpf. At 4 dpf lesions in both lines were composed of several melanocytes, indicating that the oncogene stimulates proliferation and AMN107 641571-10-0 supported the clonal expansion of the cell carrying somatic insertion of the oncogene. At 15 dpf 57.3% of the melanocytic lesions in the Et hzm1 were still expanding, whereas only 17.2% were detectable in the mitfa:Gal4-mCherry line. At 1 month 50% of the kita:Gal4-mcherry HRASV12 injected fish showed clear malignant melanoma, whereas melanomas were present in only 11% of the mitfa:Gal4-mcherry HRASV12 injected fish, indicating that many melanocytic lesions present at 15 dpf had regressed. We also compared melanoma development in double transgenic lines obtained from mitfa:Gal4 or kita:Gal4 crossed to the same UAS:GFP-HRASV12 reporter line. The ras oncogene was expressed in a similar pattern in migrating neural crest cells in both mitfa-GFP-RAS and kita-GFP-RAS double transgenic embryos at 30 hpf, but the hyper-pigmentation phenotype does not develop in the mitfa:GFP-RAS larvae.