EFFECTS OF 12-O-TETRADECANOYLPHORBOL-13-ACETATE ON THE DIFFERENTIATION OF AVIAN MELANOCYTES

Abstract

12-O-Tetradecanoylphorbol-13-acetate (TPA) inhibits and/or delays the terminal differentiation of a variety of cell types. Recently, TPA was reported to enhance melanogenesis. The effect of TPA on the differentiation of normal avian [chicken] melanocytes was studied. TPA blocked melanogenesis in normal replicating presumptive melanoblasts, and in replicating pigmented melanocytes derived from the neural crest, the retinal pigment epithelium and the pecten oculi. These normal embryonic cells failed to synthesize melanin, to assemble premelanosomes and to assume the characteristic dendritic processes of normal trunk melanocytes or the epithelioid morphology of the normal retinal pigment epithelial cell. This inhibition was remarkably reversible. Following removal of TPA, the previously blocked neural crest cells became pigmented and formed their characteristic dendritic processes, whereas the previously blocked retinal cells formed a pigmented epithelium. The effect of TPA on these normal cells was dependent on duration of exposure and degree of differentiation of the cells at the time of exposure. TPA induced the formation of elongated neurite-like processes in the amelanotic neural crest cells which differed in their cytoskeletal structure from the dendritic processes of normal trunk melanocytes. These TPA-blocked pigment cells with elongated processes bear a striking morphological resemblance to presumptive myoblasts, chondroblasts and fibroblasts treated with the tumor promoter.