Differential regulation of telomerase activity and TERT expression during brain development in mice

Telomerase is an enzyme activity consisting of a reverse transcriptase call ed TERT and an RNA component that adds repeats of a DNA sequence (TTAGGG) t o the ends of chromosomes, thereby preventing their shortening. Association s between telomerase activity and proliferation and differentiation of neur al tumor cells and neural stem cells have been reported, but the role of te lomerase in brain development is unknown. We now report analyses of telomer ase activity, TERT mRNA levels and levels of mRNAs encoding the telomere-as sociated proteins TRF1 and TRF2 in three different brain regions (brainstem , hippocampus and cerebral cortex) and the eye of mice at increasing develo pmental time points. Telomerase activity is high in the brain at embryonic day 13(E13), declines markedly between E13 and E18, remains at a low level until postnatal day 3 (P3) and becomes undetectable by P10. Surprisingly, t he temporal pattern of change in telomerase activity is not paralleled by a decrease in levels of TERT mRNA that remain elevated from E13 to P5 (with fluctuations during this time window that vary among brain regions), and th en decrease to a lower level that is maintained into adulthood. TRF1 and TR F2 mRNA levels are relatively constant throughout brain development. Our da ta are consistent with a role for telomerase activity in proliferation of n eural progenitor cells, and further suggest that TERT may play roles in neu ronal differentiation and survival. The dissociation between TERT expressio n and telomerase activity is a novel finding that suggests biological funct ions for TERT in addition to telomere maintenance. Published 2001 Wiley-Lis s, Inc.