AP2γ regulates basal progenitor fate in a region- and layer-specific manner in the developing cortex

An important feature of the cerebral cortex is its layered organization, which is modulated in an area-specific manner. We found that the transcription factor AP2γ regulates laminar fate in a region-specific manner. Deletion of AP2γ (also known as Tcfap2c) during development resulted in a specific reduction of upper layer neurons in the occipital cortex, leading to impaired function and enhanced plasticity of the adult visual cortex. AP2γ functions in apical progenitors, and its absence resulted in mis-specification of basal progenitors in the occipital cortex at the time at which upper layer neurons were generated. AP2γ directly regulated the basal progenitor fate determinants Math3 (also known as Neurod4) and Tbr2, and its overexpression promoted the generation of layer II/III neurons in a time- and region-specific manner. Thus, AP2γ acts as a regulator of basal progenitor fate, linking regional and laminar specification in the mouse developing cerebral cortex.