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Adult mammalian cortex has long been regarded as "non-neurogenic".Recent studies have reported neurogenesis in the adult cortex after cerebral ischemia,but the underlying molecular mechanisms remain elusive.Previously,we have demonstrated that in the olfactory epithelium,where neurogenesis occurs throughout the animal lifespan,chemical injury reactivates Wnt signaling in the olfactory neural stem cells.Enhancing or suppressing Wnt signaling promotes or inhibits the regeneration of olfactory sensory neurons.In this study,we investigated whether Wnt/β-catenin signaling accounted for the post-ischemic cortical neurogenesis.Focal ischemia leads to a transient wave of neurogenesis in the cortex,but most of the new born neurons die shortly after their generation.Genetic fate mapping showed that the ischemia-induced acute neurogenesis was mainly derived from local Nestin-expressing cells.To assess Wnt activation,Topgal mice,a widely accepted Wnt signaling reporter mouse line,were used.Ischemia induced a rapid increase of Wnt2 in dying neurons,and subsequent Wnt signaling activation in the surrounding Nestin-positive cells.To manipulate Wnt signaling in vivo,we injected lentivirus expressing either dominant negative TCF4 or stabilized P-catenin in the ischemic cortex to inhibit or activate Wnt signaling.The results showed that inhibiting Wnt signaling dramatically reduced the ischemia-induced neurogenesis.Forced activation of Wnt/p-catenin signaling significantly promoted neurogenesis and facilitated functional recovery.Taken together,our results suggest that Wnt/p-catenin signaling plays a crucial role in the post-ischemic cortical neurogenesis,and may serve as a potential therapeutic target for stroke.