DNA-SYNTHESIS IS INDUCED IN ADULT NEURONS AFTER EXPRESSION OF E2F1 AND E1A

DIFFERENTIATED neurons in several brain regions express the retinoblas toma (Rb) tumor supressor gene. Changing the tumor suppressor function of Rb by expressing transcription factor E2F1 and viral oncoprotein E 1A in cerebellar granular neurons in vitro and in cerebral cortical ne urons in vivo results in the induction of DNA synthesis in these neuro ns. Immunoliposome-mediated transfection of E1A and E2F1 cDNAs into th e adult cortical neurons of rats in vivo results in initiation of DNA synthesis in 5-15% of the transfected neurons. These results indicate that expression of Rb may be necessary to prevent induction of differe ntiated neurons to proliferate since many mitogenic growth factors are expressed in the brain.