Author contributions: T.R., C.H., and O.E.: conception and design, collection and/or assembly of data, data analysis and interpretation, and manuscript writing; A.C., L.R., L.M., and M.-A.M.: collection and/or assembly of data; F.D.B.: conception and design, data analysis and interpretation, manuscript writing, and final approval of manuscript.
Original Research: Tissue-Specific Stem Cells
Article first published online: 14 FEB 2012
Copyright © 2011 AlphaMed Press
Volume 30, Issue 3, pages 537–547, March 2012
How to Cite
Roque, T., Haton, C., Etienne, O., Chicheportiche, A., Rousseau, L., Martin, L., Mouthon, M.-A. and Boussin, F. D. (2012), Lack of a p21waf1/cip-Dependent G1/S Checkpoint in Neural Stem and Progenitor Cells After DNA Damage In Vivo. STEM CELLS, 30: 537–547. doi: 10.1002/stem.1010
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS December 12, 2011.
Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms
- Issue published online: 14 FEB 2012
- Article first published online: 14 FEB 2012
- Accepted manuscript online: 12 DEC 2011 02:51PM EST
- Manuscript Accepted: 1 DEC 2011
- Manuscript Received: 26 JUL 2011
- ANR-SEST (Neurorad)
- Electricité de France (EDF)
- Association pour la Recherche sur le Cancer. Grant Number: ARC3900m
- G1/S checkpoint;
- Neural stem cells;
- Ionizing radiation;
- DNA damage response;
- Cell cycle
The cyclin-dependent kinase inhibitor p21waf1/cip mediates the p53-dependent G1/S checkpoint, which is generally considered to be a critical requirement to maintain genomic stability after DNA damage. We used staggered 5-ethynyl-2′deoxyuridine/5-bromo-2′-deoxyuridine double-labeling in vivo to investigate the cell cycle progression and the role of p21waf1/cip in the DNA damage response of neural stem and progenitor cells (NSPCs) after exposure of the developing mouse cortex to ionizing radiation. We observed a radiation-induced p21-dependent apoptotic response in migrating postmitotic cortical cells. However, neural stem and progenitor cells (NSPCs) did not initiate a p21waf1/cip1-dependent G1/S block and continued to enter S-phase at a similar rate to the non-irradiated controls. The G1/S checkpoint is not involved in the mechanisms underlying the faithful transmission of the NSPC genome and/or the elimination of critically damaged cells. These processes typically involve intra-S and G2/M checkpoints that are rapidly activated after irradiation. p21 is normally repressed in neural cells during brain development except at the G1 to G0 transition. Lack of activation of a G1/S checkpoint and apoptosis of postmitotic migrating cells after DNA damage appear to depend on the expression of p21 in neural cells, since substantial cell-to-cell variations are found in the irradiated cortex. This suggests that repression of p21 during brain development prevents the induction of the G1/S checkpoint after DNA damage. STEM CELLS 2012;30:537–547