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.
Ingraham
C A
CA
Department of Biochemistry, University of North Carolina School of Medicine, Chapel Hill 27514.
Cox
M E
ME
Ward
D C
DC
Fults
D W
DW
Maness
P F
PF
D000818:Animals; D002454:Cell Differentiation; D002642:Chick Embryo; D005314:Embryonic and Fetal Development; D005786:Gene Expression Regulation; D009420:Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D016392:Proto-Oncogene Proteins pp60(c-src); D011519:Proto-Oncogenes
D011518:Proto-Oncogene Proteins; D016392:Proto-Oncogene Proteins pp60(c-src)