Pbx Regulates Patterning of the Cerebral Cortex in Progenitors and Postmitotic Neurons

•Pbx1/2 function in progenitors and neurons patterns the prefrontal cortex•Pbx1/2 function in progenitors regulates D/V patterning•Pbx1/2 regulates cortical lamination of the frontal cortex through Reelin repression•PBX directly regulates cortical promoters and enhancers

SummaryWe demonstrate using conditional mutagenesis that Pbx1, with and without Pbx2+/− sensitization, regulates regional identity and laminar patterning of the developing mouse neocortex in cortical progenitors (Emx1-Cre) and in newly generated neurons (Nex1-Cre). Pbx1/2 mutants have three salient molecular phenotypes of cortical regional and laminar organization: hypoplasia of the frontal cortex, ventral expansion of the dorsomedial cortex, and ventral expansion of Reelin expression in the cortical plate of the frontal cortex, concomitant with an inversion of cortical layering in the rostral cortex. Molecular analyses, including PBX ChIP-seq, provide evidence that PBX promotes frontal cortex identity by repressing genes that promote dorsocaudal fate.