Variation of radiation-sensitivity of neural stem and progenitor cell populations within the developing mouse brain

Abstract

Purpose: 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.

Material and 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.

Keywords::

• Neural stem and progenitor cells
• G1/S checkpoints
• radiation-induced apoptosis
• radialglial cells
• intermediate progenitors

Acknowledgements

The authors would like to thanks V. Neuville and J. Tilliet for their technical assistance in the animal facilities, C. Joubert and all the members of Laboratoire de Radiopathologie for helpful discussions. We are also very grateful to J. D. Godin and F. Cordelières for the ImageJ plugin.

Declaration of interest: The authors report no declaration of interest. The authors alone are responsible for the content and writing of the paper.

This work was sustained by grants of Agence Nationale de la Recherche-Santé Environnement Santé Travail (ANR-SEST)-Neurorad and Electricité de France.