Variation of radiation-sensitivity of neural stem and progenitor cell populations within the developing mouse brain.
OBJECTIVE
We investigated the DNA damage response (DDR) of fetal neural stem and progenitor cells (NSPC), since exposure to ionizing radiation can severely impair the brain development.


METHODS
We compared apoptosis induction in the dorsal telencephalon and the lateral ganglionic eminences (LGE) of mouse embryos after an in utero irradiation. We used two thymidine analogs, together with the physical position of nuclei within brain structures, to determine the fate of irradiated NSPC.


RESULTS
NSPC did not activate an apparent protein 21(p21)- dependent G1/S checkpoint within the LGE as their counterparts within the dorsal telencephalon. However, the levels of radiation-induced apoptosis differed between the two telencephalic regions, due to the high radiation sensitivity of intermediate progenitors of the LGE. Besides radial glia cells, that function as neural stem cells, were more resistant and were reoriented toward self-renewing within hours following irradiation.


CONCLUSIONS
The lack of the p21-dependent-cell cycle arrest at the G1/S transition appears to be a general feature of NSPC in the developing brain. However, we found variation of radiation-response in function of the types of NSPC. Factors involved in DDR and those involved in the regulation of neurogenesis are intricately linked in determining the cell fate after irradiations.
CEA DSV iRCM SCSR, Laboratoire de Radiopathologie, INSERM, U967, Université Paris Diderot, Sorbonne Paris Cité, UMR 967, and Université Paris Sud , UMR 967, F-92265 Fontenay-aux-Roses, France.
Olivier
O
Etienne
Telma
T
Roque
Celine
C
Haton
François D
FD
Boussin
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D001921:Brain / Q000166:cytology* / Q000196:embryology* / Q000528:radiation effects; D059447:Cell Cycle Checkpoints / Q000528:radiation effects; D002454:Cell Differentiation / Q000528:radiation effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004249:DNA Damage; D005260:Female; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects*; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D011836:Radiation Tolerance / Q000528:radiation effects*; D013687:Telencephalon / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D013997:Time Factors
D050759:Cyclin-Dependent Kinase Inhibitor p21