The Telomerase Reverse Transcriptase (TERT) and p53 Regulate Mammalian PNS and CNS Axon Regeneration downstream of c-Myc

Abstract

Although several genes have been identified to promote axon regeneration in the central nervous system, our understanding of the molecular mechanisms by which mammalian axon regeneration is regulated is still limited and fragmented. Here by using sensory axon and optic nerve regeneration as model systems, we revealed an unexpected role of telomerase reverse transcriptase (TERT) in regulation of axon regeneration. We also provided strong evidence that TERT and p53 acted downstream of c-Myc to control sensory axon regeneration. More importantly, overexpression of p53 in sensory neurons and retinal ganglion cells (RGCs) was sufficient to promote sensory axon and optic never regeneration, respectively. The study revealed a novel c-Myc-TERT-p53 signaling pathway, expanding horizons for novel approaches promoting CNS axon regeneration.