Ischemic stroke causes massive neuronal loss in the brain, leading to persistent neurological deficits. After brain morphogenesis during development, new neurons can be generated only in several areas including the ventricular-subventricular zone (V-SVZ) located at the walls of lateral ventricles. While the newly-generated neurons in the V-SVZ migrate toward the infarct area to replace damaged neurons, the regenerative response is insufficient to induce functional recovery. We are studying the mechanisms of neuronal regeneration using a mouse model for ischemic stroke. Immediately after stroke, local astrocytes a major glial population become hypertrophic and proliferative. We found that the V-SVZ-derived new neurons use a diffusible protein Slit1 to migrate toward the lesion passing through the meshwork of astrocytic processes. Lentivirus-mediated Slit1 overexpression in the new neurons transplanted into the post-stroke brain migrated closer to the lesion than the control neurons, where they mature into multiple types of neurons depending on their positioning 5-10 weeks later. These results suggest that manipulating interactions with astrocytes is critical for fate determination of the new neurons, which will be critical for functional neuronal regeneration in stem/progenitor cell-based therapies for brain injury.