ANALYSIS OF CELL CYCLE-RELATED GENE-EXPRESSION IN POSTMITOTIC NEURONS - SELECTIVE INDUCTION OF CYCLIN D1 DURING PROGRAMMED CELL-DEATH

Sympathetic neurons undergo RNA and protein synthesis-dependent programmed cell death when deprived of nerve growth factor. To test the hypothesis that neuronal programmed cell death is a consequence of conflicting growth signals which cause the inappropriate activation of cell cycle genes, we have analyzed cell cycle-related genes for their expression in postmitotic neurons. Surprisingly, many of these genes are expressed in neurons, although cdc2, cdk2, and cyclin A are not. During programmed cell death, the expression of most of these genes, including several cyclins and the Rb and p53 tumor suppressor genes, decreases similar to that of neuronal genes. In contrast, cyclin D1 expression is selectively induced in dying neurons. Cyclin D1 mRNA levels peak 15-20 hr after nerve growth factor withdrawal, concurrent with the time that neurons become committed to die. These results provide an extensive characterization of cell cycle gene expression in postmitotic neurons and provide the evidence for a gene induced during neuronal programmed cell death.