Growth factors in mammalian embryogenesis

Malignant murine embryonal carcinoma (EC) cells have been studied as a means of characterizing the identity and action of growth regulatory molecules in the early postimplantation mouse embryo. The differentiation of EC cells in vitro is accompanied by significant changes in the control of cell proliferation, including the acquisition of dependence on specific exogenous growth factors for cell multiplication. This is at least partly controlled by the developmentally regulated expression of specific growth factor receptors and their intracellular response systems. The development of defined media has allowed the identification of the principal factors required for EC cell proliferation in vitro. These factors are synthesized in vivo by the extra-embryonic tissues of the developing embryo and by the differentiated progeny of EC cells in vitro. EC cells secrete a potent growth factor (embryonal carcinoma-derived growth factor, ECDGF) which has been purified and partly characterized. ECDGF induces proliferation of the differentiated progeny of EC cells and specific normal embryonic cell types in vitro, suggesting that ECDGF may act as an embryonic growth factor in vivo. Together these findings suggest that proliferation in the embryo may be controlled by reciprocal interaction between primitive ectoderm cells and their differentiated derivatives, mediated by the developmentally regulated expression of specific soluble growth factors.