Distinct and different effects of the oncogenes v-myc and v-src on avian sympathetic neurons: retroviral transfer of v-myc stimulates neuronal proliferation whereas v-src transfer enhances neuronal differentiation.
Immature avian sympathetic neurons are able to proliferate in culture for a limited number of divisions albeit expressing several neuron-specific properties. The effect of avian retroviral transfer of oncogenes on proliferation and differentiation of sympathetic neurons was investigated. Primary cultures of 6-d-old quail sympathetic ganglia, consisting of 90% neuronal cells, were infected by Myelocytomatosis virus (MC29), which contains the oncogene v-myc, and by the v-src-containing Rous sarcoma virus (RSV). RSV infection, in contrast to findings in other cellular systems, resulted in a reduction of neuronal proliferation as determined by 3H-thymidine incorporation (50% of control 4 d after infection) and in increased morphological differentiation. This is reflected by increased neurite production, cell size, and expression of neurofilament protein. In addition, RSV-infected neurons, unlike uninfected cells, are able to survive in culture for time periods up to 14 d in the absence of added neurotrophic factors. In contrast, retroviral transfer of v-myc stimulated the proliferation of immature sympathetic neurons preserving many properties of uninfected cells. The neuron-specific cell surface antigen Q211 and the adrenergic marker enzyme tyrosine hydroxylase were maintained in MC29-infected cells and in the presence of chick embryo extract the cells could be propagated over several weeks and five passages. Within 7 d after infection, the number of Q211-positive neurons increased approximately 100-fold. These data demonstrate distinct and different effects of v-src and v-myc-containing retroviruses on proliferation and differentiation of sympathetic neurons: v-src transfer results in increased differentiation, whereas v-myc transfer maintains an immature status reflected by proliferation, immature morphology, and complex growth requirements. The possibility of expanding immature neuronal populations by transfer of v-myc will be of considerable importance for the molecular analysis of neuronal proliferation and differentiation.
Haltmeier
H
H
Max-Planck-Institut für Psychiatrie, Federal Republic of Germany.
Rohrer
H
H
D000818:Animals; D009189:Avian Myeloblastosis Virus / Q000235:genetics; D001358:Avian Sarcoma Viruses / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D005728:Ganglia, Sympathetic / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D016274:Oncogene Protein p55(v-myc); D015688:Oncogene Protein pp60(v-src) / Q000494:pharmacology*; D011784:Quail; D015682:Retroviridae Proteins, Oncogenic / Q000494:pharmacology*; D014020:Tissue Extracts / Q000494:pharmacology; D014162:Transfection
D016274:Oncogene Protein p55(v-myc); D015682:Retroviridae Proteins, Oncogenic; D014020:Tissue Extracts; D015688:Oncogene Protein pp60(v-src)