a, Hematoxylin and eosin-stained transverse sections of zebrafish melanomas at two weeks post onset. At this time point dorsal miniCoopR-EGFP melanomas (left) display exophytic growth, whereas miniCoopR-SETDB1 melanomas (right) have invaded from the skin, through the collagen-rich stratum compactum of the dermis (sc), into the underlying musculature. Scale bar = 70μm. b,
SETDB1 interacts with BRAF(V600E) to affect pigmentation pattern, but a p53(lf) mutation is required to form melanomas. MiniCoopR-EGFP or MiniCoopR-SETDB1 was injected into the indicated transgenic strains. Percentages indicate melanoma incidence at 12 weeks of age. c,
SETDB1abrogates BRAF(V600E)-induced senescence. Left, brightfield pseudocolored photomicrographs of SA-βGal staining performed on scale-associated melanocytes. Middle and right, fluorescent photomicrographs of the same melanocytes. miniCoopR-rescued melanocytes in this experiment express mitfa promoter-driven EGFP (middle) and the MITFA protein (right). Multiple nuclei (arrowheads) are present in BRAF(V600E)-expressing melanocytes. Percentage of senescent melanocytes is indicated at left (p = 7.3×10-51, χ2). Scale bar = 10μm.