Previous studies have shown that reactive glial cells in the cortex can be reprogrammed to produce neurons after injury in vivo, but whether these induced neurons can adequately replace or compensate for the lost neurons is unknown. Mattugini et al. find that virally driven expression of two proneural factors, neurogenin 2 and NURR1, in mouse cortical astrocytes located in the cortical grey matter is sufficient to reprogram the cells into neurons after a stab wound injury. Importantly, the induced neurons exhibited molecular and morphological hallmarks of cortical pyramidal neurons that were appropriate to the cortical laminae in which they were located and formed long-distance axonal projections to relevant downstream brain regions.