c-src and other proto-oncogenes implicated in neuronal differentiation.

The proto-oncogene c-src has been implicated in the development and mature function of the nervous system. pp60c-src, the protein product of the c-src gene, is a tyrosine protein kinase that is highly enriched in fetal neural tissue. pp60c-src appears in two phases of neuronal development. Neuroectodermal cells of gastrulating embryos first express pp60c-src around the time of commitment to neuronal or glial pathways. Later, committed neuroepithelial cells express pp60c-src near the onset of terminal neuronal differentiation. Immunocytochemical analyses of pp60c-src in developing chick retina, telencephalon, and cerebellum show immunoreactivity concentrated in regions rich in growth cones and neurites. Moreover, pp60c-src is concentrated approximately 10-fold in a biochemical fraction from fetal rat brain that is enriched in nerve growth cone membranes. These results point toward a function for pp60c-src in neurite outgrowth. A functional role for other proto-oncogenes in the development of the nervous system was indicated from a study of the expression of a battery of proto-oncogenes during the retinoic acid-induced differentiation of the mouse embryonal carcinoma cell line P19 to a neuronal phenotype. Nuclear runoff transcription of the proto-oncogenes c-src, c-fms, c-sis, N-ras, c-myc, and c-fos was observed in proliferating and retinoic acid-treated cells.