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

Oncogene volume 19, pages 2957–2966 (2000)Cite this article

Abstract

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.

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Abbreviations

NPC:

neural precursor cells

FGF2:

fibroblast growth factor 2

NGF:

nerve growth factor

TERT:

telomerase reverse transcriptase protein

TER:

telomerase RNA

AZT:

3′-azido-2′,3′-dideoxythymidine

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Author notes

  1. Stéphane Haïk and Laurent R Gauthier: S Haik and LR Gauthier contributed equally to this work

Authors and Affiliations

  1. CEA, Service de Neurovirologie DSV/DRM, CRSSA, IPSC, BP 6, 92 265 Fontenay-aux-Roses cedex, France

    Stéphane Haïk, Jean-Michel Peyrin & Dominique Dormont

  2. CEA, Laboratoire de RadioPathologie DSV/DRR, IPSC, BP 6, 92 265 Fontenay-aux-Roses cedex, France

    Laurent R Gauthier, Christine Granotier, Céline Silva Lages & François D Boussin

Authors
  1. Stéphane Haïk
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  2. Laurent R Gauthier
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  3. Christine Granotier
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  4. Jean-Michel Peyrin
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  5. Céline Silva Lages
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  6. Dominique Dormont
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  7. François D Boussin
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Haïk, S., Gauthier, L., Granotier, C. et al. Fibroblast growth factor 2 up regulates telomerase activity in neural precursor cells. Oncogene 19, 2957–2966 (2000). https://doi.org/10.1038/sj.onc.1203596

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