Control of muscle and neuronal differentiation in a cultured embryonal carcinoma cell line

Pluripotent murine embryonal carcinoma cells can differentiate in culture into many tissue types similar to those normally found in early embryos and may be useful in investigating some developmental events. Central to our understanding of embryonic development are explanations of cellular determination, that is, the commitment of early embryonic cells to form divergent cell types. Of relevance is recent work with the F9 line of embryonal carcinoma cells which suggests that certain extra-embryonic cell types are specifically formed following treatment of undifferentiated cells with drugs and the manipulation of culture conditions. We report here that the P19 line of embryonic carcinoma cells may provide and analogous system in which drugs can be used to manipulate the formation of tissues which normally comprise the fetus. In the presence of dimethyl sulphoxide (DMSO) aggregates of P19 cells differentiate rapidly to form large amounts of cardiac and skeletal muscle but no neurones or glia. We have previously shown that in the presence of high concentrations of retinoic acid (greater than 5 x 10(-7) M), aggregates of these same cells develop into neuronal and glial tissues but not muscle. Thus, drugs can be used to generate two quite different spectra of embryonic tissue types from the same population of embryonal carcinoma cells.