Foxp1 controls neural stem cell competence and bias towards deep layer cortical fates

Abstract

SUMMARYThe laminar architecture of the mammalian neocortex depends on the orderly generation of distinct neuronal subtypes by apical radial glia (aRG) during embryogenesis. We identify critical roles for Foxp1 in maintaining RG identity and gating the temporal competency for early neurogenesis. High levels of Foxp1 are associated with early aRG and are required to promote proliferation and influence cell division symmetry, favoring aRG expansion and production of early born neurons. The potent pro-progenitor functions of Foxp1 are revealed through its ability to preserve a population of cells with aRG identity throughout development and extend the early neurogenic period into postnatal life. Foxp1 further promotes the formation of cells resembling basal RG (bRG), a progenitor group implicated in the increased size and complexity of the human cortex. Consistent with this role, we show that FOXP1 is associated with the initial formation and expansion of bRG during human corticogenesis.HIGHLIGHTSFoxp1 is transiently expressed by aRG during the early phase of corticogenesisFoxp1 promotes self-renewing vertical cell divisions and aRG maintenanceFoxp1 gates the time window of deep layer neurogenesisEctopic Foxp1 expression can elicit bRG formation