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.
Int J Radiat Biol. 2012 Oct;88(10):694-702. doi: 10.3109/09553002.2012.710927. Epub 2012 Aug 7.
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.
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.
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.
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.
我们研究了胎儿神经干细胞和祖细胞（NSPC）的 DNA 损伤反应（DDR），因为暴露于电离辐射会严重损害大脑发育。
我们比较了胚胎在子宫内照射后，背侧端脑和外侧神经节隆起（LGE）中的细胞凋亡诱导情况。我们使用了两种胸苷类似物，并结合脑结构内核的物理位置，来确定照射后 NSPC 的命运。
NSPC 并没有在 LGE 中激活明显的依赖于蛋白 21（p21）的 G1/S 检查点，而在背侧端脑中的 NSPC 则会激活该检查点。然而，由于 LGE 中间祖细胞对辐射的高度敏感性，两个端脑区域的辐射诱导凋亡水平存在差异。除了作为神经干细胞的放射状胶质细胞之外，它们在照射后数小时内会重新定向自我更新，从而具有更高的辐射抗性。
在 G1/S 转换处缺乏依赖于 p21 的细胞周期阻滞似乎是发育中大脑中 NSPC 的普遍特征。然而，我们发现辐射反应的功能在 NSPC 的类型上存在差异。参与 DDR 的因素和参与神经发生调节的因素在确定照射后细胞命运方面紧密相关。
