Fibroblast growth factor 2 up regulates telomerase activity in neural precursor cells

During brain development, neuronal and glial cells are generated from neura l precursors on a precise schedule involving steps of proliferation, fate c ommitment and differentiation. We report that telomerase activity is highly expressed during embryonic murine cortical neurogenesis and early steps of gliogenesis and progressively decreases thereafter during cortex maturatio n to be undetectable in the normal adult brain. We evidenced neural precurs or cells (NPC) as the principal telomerase-expressing cells in primary cult ures from E15 mouse embryo cortices, Their differentiation either in neuron s or in glial cells lead to a down regulation of telomerase activity that w as directly correlated to the decrease of telomerase core protein (mTERT) m RNA synthesis. Furthermore, we show that FGF2 (fibroblast growth factor 2), one of the main regulators of CNS development, induces a dose-dependant in crease of both the proliferation of NPC and telomerase activity in primary cortical cultures without affecting the mTERT mRNA synthesis compared to th at of glyceraldehyde-3-phosphate dehydrogenase (mGAPDH). Finally, we eviden ced that AZT (3'-azido-2',3'-dideoxythymidine), known to inhibit telomerase activity, blocks in a dose dependant manner the FGF2-induced proliferation of NPC. Altogether, our results are in favor of an important role of telom erase activity during brain organogenesis.