Induction of DNA replication in adult rat neurons by deregulation of the retinoblastoma/E2F G(1) cell cycle pathway

In adult organisms, a range of proliferative capacities are exhibited by di fferent cell types. Stem cell populations in many tissues readily enter the cell cycle when presented with serum growth factors or other proliferative cues, whereas "terminally" postmitotic cells, such as cardiac myocytes and neurons, fail to do so. Although they rarely show evidence of a proliferat ive capacity in vivo, there is accumulating evidence to suggest that DNA sy nthesis can be triggered in postmitotic cells. We now show that cultured ad ult rat sensory neurons can replicate DNA in response to ectopic expression of E2F1 or E2F2 and that this is augmented by expression of cyclin-depende nt kinase activities. We also find that addition of serum and laminin inhib its the E2F-induced S-phase in neurons but not in nonneuronal cells in the same cultures. We conclude that, although terminally differentiated neurons possess the capacity to reinitiate DNA replication in response to G(1) reg ulatory activities, they fail to do so in the presence of signals that do n ot inhibit S-phase in other cell types in the same cultures. This suggests the existence of cell type-specific inhibitory pathways induced by these si gnals.