Neurons are generated continuously throughout life in the subgranular zone of the dentate gyrus in the hippocampus. Adult neurogenesis is regulated by both intrinsic and extrinsic signals. It is suggested to play crucial roles in learning and memory as well as mood modulation. Moreover, its dysfunction can lead to neurological disorders such as autism, epilepsy, and schizophrenia.

Rho GTPases are important regulators of adult hippocampal neurogenesis, and their functions are tightly controlled by regulatory factors including Rho GTPase-activating proteins (Rho GAPs). While Rho GAPs regulate neuronal differentiation, neurite outgrowth, and migration during central nervous system development, it is largely unknown whether they are involved in the regulation of adult neurogenesis....[ Read more ]

Neurons are generated continuously throughout life in the subgranular zone of the dentate gyrus in the hippocampus. Adult neurogenesis is regulated by both intrinsic and extrinsic signals. It is suggested to play crucial roles in learning and memory as well as mood modulation. Moreover, its dysfunction can lead to neurological disorders such as autism, epilepsy, and schizophrenia.

Rho GTPases are important regulators of adult hippocampal neurogenesis, and their functions are tightly controlled by regulatory factors including Rho GTPase-activating proteins (Rho GAPs). While Rho GAPs regulate neuronal differentiation, neurite outgrowth, and migration during central nervous system development, it is largely unknown whether they are involved in the regulation of adult neurogenesis. Here, we report the role of α2-chimaerin, a Rho-GAP, in adult neurogenesis. The results showed that α2-chimaerin–knockout mice exhibited impaired adult hippocampal neurogenesis. This effect was mediated by the regulation of the premature differentiation of neural progenitor cells (NPCs). Conditional knockout of α2-chimaerin in NPCs switched their division mode from asymmetric to symmetric, resulting in the depletion of the neural stem cell/NPC pool and decreased adult neurogenesis in the long term. Moreover, deficiency of α2-chimaerin attenuated the dendritic development of adult-born neurons in the dentate gyrus and induce anxiety/depression like behavior under stress conditions. Thus, our findings demonstrate the functional roles of Rho GAPs in adult neurogenesis and advance our understanding of the biology of adult stem cells.