A transcriptional program underlying neuronal Survival

A shift of the delicate balance between apoptosis and survival-inducing signals determines the fate of neurons during the development of the central nervous system and in its homeostasis throughout adulthood. Both apoptosis- and survival-signaling pathways converge into the nucleus and regulate gene expression. Although the transcriptional program of neuronal apoptosis has been elucidated, the transcriptional program underlying neuronal survival is still unknown. We conducted whole-genome expression profiling to decipher the transcriptional regulatory elements controlling the apoptotic/survival switch in cerebellar granule neurons following the induction of apoptosis by serum and potassium deprivation and the rescue by different neurotrophic factors. Although acting through different upstream signaling pathways, the survival effects of neurotrophic factors converged to common transcriptional cascades. In addition to revealing the existence of a previously unknown transcriptional program underlying neuronal survival, our analysis identified common transcriptional changes intersecting neuronal apoptosis and survival, forming the basis for further functional analyses and pharmacological investigation.