TELOMERE REDUCTION AND TELOMERASE INACTIVATION DURING NEURONAL CELL-DIFFERENTIATION

Telomerase adds (TTAGGG)(n) hexanucleotide repeats to the ends of mamm alian telomeres. This compensates for telomeric loss with successive r ounds of cellular replication. Telomerase activity is detected in many neoplastic cells, but not in most normal somatic cells. To determine whether telomeric length and telomerase activity are associated with c ellular differentiation, we measured telomeric lengths and telomerase activity in embryonic NT2 precursor cells prior to and following diffe rentiation into post mitotic hNT neurons. This system allows for studi es in a direct neuronal cell lineage and, thus, provides a unique mode l for studying the role of neuronal telomerase activity. Our results s how that telomerase activity was present in precursor cells, but not i n neuronal cells. Telomeres were consistently longer in NT2 cells than in hNT cells. These results suggest that changes in telomeric length and loss of telomerase activity play a role in neuronal cellular diffe rentiation. (C) 1996 Academic Press, Inc.