ECTOPIC EXPRESSION OF MITF, A GENE FOR WAARDENBURG SYNDROME TYPE-2, CONVERTS FIBROBLASTS TO CELLS WITH MELANOCYTE CHARACTERISTICS

MITF (microphthalmia-associated transcription factor) encodes a transc ription factor with a basic-helix-loop-helix-zipper (bHLH-Zip) motif. MITF mutations occur in patients with Waardenburg syndrome type 2, a d isorder associated with melanocyte abnormalities. Here we show that ec topic expression of MITF converts NIH/3T3 fibroblasts into cells with characteristics of melanocytes. MITF transfectants formed foci of morp hologically altered cells, which resemble those induced by oncogenes, but did not exhibit malignant phenotypes. Instead, they contained dend ritic cells that express melanogenic marker proteins such as tyrosinas e and tyrosinase-related protein 1. Most cloned cells of MITF transfec tants exhibited dendritic morphology and expressed melanogenic markers , but such properties were not observed in cells transfected with clos ely related TFE3 cDNA. Our findings indicate that MITF is critically i nvolved in melanocyte differentiation.