Vandenbosch Renaud, Borgs Laurence, Beukelaers Pierre, Foidart Agnès, Nguyen Laurent, Moonen Gustave, Berthet Cyril, Kaldis Philipp, Gallo Vittorio, Belachew Shibeshih, Malgrange Brigitte
Center for Cellular and Molecular Neuroscience, University of Liège, Liège, Belgium.
Cell Cycle. 2007 Dec 15;6(24):3065-9. doi: 10.4161/cc.6.24.5048. Epub 2007 Sep 14.
Granule neurons of the dentate gyrus (DG) of the hippocampus undergo continuous renewal throughout life. Among cell cycle regulators, cyclin-dependent kinase 2 (Cdk2) is considered as a major regulator of S-phase entry. We used Cdk2-deficient mice to decipher the requirement of Cdk2 for the generation of new neurons in the adult hippocampus. The quantification of cell cycle markers first revealed that the lack of Cdk2 activity does not influence spontaneous or seizure-induced proliferation of neural progenitor cells (NPC) in the adult DG. Using bromodeoxyuridine incorporation assays, we showed that the number of mature newborn granule neurons generated de novo was similar in both wild-type (WT) and Cdk2-deficient adult mice. Moreover, the apparent lack of cell output reduction in Cdk2(-/-) mice DG did not result from a reduction in apoptosis of newborn granule cells as analyzed by TUNEL assays. Our results therefore suggest that Cdk2 is dispensable for NPC proliferation, differentiation and survival of adult-born DG granule neurons in vivo. These data emphasize that functional redundancies between Cdks also occur in the adult brain at the level of neural progenitor cell cycle regulation during hippocampal neurogenesis.
海马齿状回（DG）的颗粒神经元在整个生命过程中持续更新。在细胞周期调节因子中，细胞周期蛋白依赖性激酶2（Cdk2）被认为是进入S期的主要调节因子。我们使用Cdk2基因缺失的小鼠来解读Cdk2对成年海马中新神经元生成的必要性。对细胞周期标记物的定量分析首先表明，缺乏Cdk2活性并不影响成年DG中神经祖细胞（NPC）的自发增殖或癫痫诱导的增殖。通过溴脱氧尿苷掺入试验，我们发现野生型（WT）成年小鼠和Cdk2基因缺失成年小鼠中从头生成的成熟新生颗粒神经元数量相似。此外，通过TUNEL试验分析发现，Cdk2（-/-）小鼠DG中明显缺乏细胞输出减少并非源于新生颗粒细胞凋亡的减少。因此，我们的结果表明，Cdk2对于成年DG颗粒神经元在体内的NPC增殖、分化和存活并非必需。这些数据强调，在海马神经发生过程中，成年大脑在神经祖细胞周期调节水平上也存在Cdk之间的功能冗余。
