Fibroblast growth factor 2 up regulates telomerase activity in neural precursor cells.
During brain development, neuronal and glial cells are generated from neural precursors on a precise schedule involving steps of proliferation, fate commitment 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 maturation to be undetectable in the normal adult brain. We evidenced neural precursor cells (NPC) as the principal telomerase-expressing cells in primary cultures from E15 mouse embryo cortices. Their differentiation either in neurons or in glial cells lead to a down regulation of telomerase activity that was directly correlated to the decrease of telomerase core protein (mTERT) mRNA synthesis. Furthermore, we show that FGF2 (fibroblast growth factor 2), one of the main regulators of CNS development, induces a dose-dependant increase of both the proliferation of NPC and telomerase activity in primary cortical cultures without affecting the mTERT mRNA synthesis compared to that of glyceraldehyde-3-phosphate dehydrogenase (mGAPDH). Finally, we evidenced 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 telomerase activity during brain organogenesis. Oncogene (2000).
Haïk
S
S
CEA, Service de Neurovirologie DSV/DRM, CRSSA, IPSC, BP 6, 92 265 Fontenay-aux-Roses cedex, France.
Gauthier
L R
LR
Granotier
C
C
Peyrin
J M
JM
Lages
C S
CS
Dormont
D
D
Boussin
F D
FD
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000201:enzymology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D017931:DNA Primers; D004268:DNA-Binding Proteins; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012313:RNA; D012333:RNA, Messenger / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology*; D015215:Zidovudine / Q000494:pharmacology
D017931:DNA Primers; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D018894:Reverse Transcriptase Inhibitors; C422952:telomerase RNA; D016222:Fibroblast Growth Factor 2; D015215:Zidovudine; D012313:RNA; D019098:Telomerase