Differentiation apparently repressed by the nucleus. Rapidly-induced pigmentation of enucleated melanoma cells

There is evidence for cytoplasmic control over gene expression in cell differentiation, but still very little is known of the intracellular mechanism, nuclear, cytoplasmic, or both, which actively initiates the differentiation of one cell type into another. Here the role of the cytoplasm was examined in the induction of differentiation of cultured mouse melanoma cells by melanocyte-stimulating hormone and alkaline medium. Intact cells were compared with cytoplasts, cells enucleated by centrifugation in the presence of cytochalasin D (CD). Surprisingly, early inductions of pigment (melanin) synthesis and of the principal melanin-synthesizing enzyme activity, tyrosinase, could be achieved in cytoplasts. Indeed these early changes were slower in nucleated cells and were accelerated by the inhibitor of protein synthesis, cycloheximide. Thus the initial activation of tyrosinase and melanin synthesis--although not necessarily any other or later aspects of melanoma cell differentiation--is apparently controlled through a labile, transcription- and translation-dependent repression. To our knowledge this is a novel mechanism for the initiation of differentiation; its generality remains to be tested.