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Updated: May 20, 2026
Assessing Cell Cycle Progression of Neural Stem and Progenitor Cells in the Mouse Developing Brain after Genotoxic Stress
Published on: May 7, 2014
Variation of radiation-sensitivity of neural stem and progenitor cell populations within the developing mouse brain
Olivier Etienne1, Telma Roque, Celine Haton
1CEA 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.
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.
Insights
Fetal neural stem cells show varied responses to radiation. While lacking a p21-dependent cell cycle arrest, their DNA damage response differs, impacting brain development.
Area of Science:
- Developmental neuroscience
- Radiation biology
- Cellular biology
Background:
- Ionizing radiation exposure during development can significantly disrupt fetal brain development.
- Neural stem and progenitor cells (NSPC) are crucial for brain formation and are vulnerable to radiation damage.
Purpose of the Study:
- To investigate the DNA damage response (DDR) in fetal neural stem and progenitor cells (NSPC) following in utero irradiation.
- To compare the cellular responses and fates of NSPC in different developing brain regions after radiation exposure.
Main Methods:
- Comparison of apoptosis induction in dorsal telencephalon and lateral ganglionic eminences (LGE) of mouse embryos post-irradiation.
- Utilized thymidine analogs and nuclear positioning to track the fate of irradiated NSPC.
Main Results:
- NSPC in the LGE did not exhibit a p21-dependent G1/S checkpoint activation, unlike those in the dorsal telencephalon.
- Regional differences in apoptosis were observed, with LGE intermediate progenitors showing high radiation sensitivity.
- Radial glia cells, acting as neural stem cells, demonstrated radioresistance and reoriented towards self-renewal post-irradiation.
Conclusions:
- The absence of p21-dependent cell cycle arrest is a common characteristic of NSPC in the developing brain.
- Radiation response varies among different NSPC types, highlighting heterogeneity in cellular sensitivity.
- Factors governing DNA damage response and neurogenesis are interconnected in determining cell fate after irradiation.
