Brain Research Institute, Faculty of Medicine, University of Zurich, CH-8057 Zurich, Switzerland.
J Neurosci. 2013 Jan 16;33(3):1179-89. doi: 10.1523/JNEUROSCI.2103-12.2013.
The molecular mechanisms underlying the generation, maturation, and integration of new granule cells generated throughout life in the mammalian hippocampus remain poorly understood. Small Rho GTPases, such as Cdc42 and Rac1, have been implicated previously in neural stem/progenitor cell (NSPC) proliferation and neuronal maturation during embryonic development. Here we used conditional genetic deletion and virus-based loss-of-function approaches to identify temporally distinct functions for Cdc42 and Rac1 in adult hippocampal neurogenesis. We found that Cdc42 is involved in mouse NSPC proliferation, initial dendritic development, and dendritic spine maturation. In contrast, Rac1 is dispensable for early steps of neuronal development but is important for late steps of dendritic growth and spine maturation. These results establish cell-autonomous and stage-specific functions for the small Rho GTPases Cdc42 and Rac1 in the course of adult hippocampal neurogenesis.
哺乳动物海马体中终生产生的新颗粒细胞的产生、成熟和整合的分子机制仍知之甚少。小 Rho GTPases，如 Cdc42 和 Rac1，先前已被牵连到胚胎发育过程中的神经干细胞/祖细胞（NSPC）增殖和神经元成熟。在这里，我们使用条件性基因缺失和基于病毒的功能丧失方法来鉴定 Cdc42 和 Rac1 在成年海马神经发生中的时间上不同的功能。我们发现 Cdc42 参与了小鼠 NSPC 的增殖、初始树突发育和树突棘成熟。相比之下，Rac1 对于神经元发育的早期步骤是可有可无的，但对于树突生长和棘突成熟的后期步骤是重要的。这些结果确立了小 Rho GTPases Cdc42 和 Rac1 在成年海马神经发生过程中的细胞自主和阶段特异性功能。
