Ras p21 protein promotes survival and differentiation of human embryonic neural crest-derived cells

We have previously shown that the oncogene product p21 Ras is essential for the survival and neurite outgrowth-promoting activity of nerve growth factor on cultured chick embryonic sensory, but not sympathetic neurons. In order to extend our observations to the human system and to non-neuronal cells, we introduced the oncogenic form of p21 Ras into the cytoplasm of three different types of cultured human embryonic neural crest derivatives (8th-11th gestational week): dorsal root ganglion neurons, sympathetic neurons, and adrenal chromaffin cells. These cells are dependent on nerve growth factor for survival and/or fibre outgrowth in vitro. In dorsal root ganglion neurons, p21 Ras promoted survival and fibre outgrowth which was quantitatively and qualitatively comparable to the nerve growth factor effect (84% vs. 95%, control 18%). Sympathetic neurons showed a similar effect, albeit with a higher background survival (91% vs. 93%, control 58%). On chromaffin cells, which respond to nerve growth factor with pronounced fibre outgrowth in culture, the effect of p21 Ras was again comparable to that of nerve growth factor (35% vs. 30%, control 5%). The survival and fibre outgrowth-promoting effects of p21 Ras on human embryonic dorsal root ganglion neurons, sympathetic neurons and chromaffin cells suggest an involvement of p21 Ras in the intracellular signal transduction of nerve growth factor in human neural crest-derived cell populations.