Fezf2 Expression Identifies a Multipotent Progenitor for Neocortical Projection Neurons, Astrocytes, and Oligodendrocytes

• Fezf2+ RGCs exist throughout cortical neurogenesis
• Fezf2+ RGCs sequentially generate cortical projection neuron subtypes and glia
• Cux2-Cre/CreERT2-labeled RGCs generate deep- and upper-layer projection neurons

SummaryProgenitor cells in the cerebral cortex sequentially generate distinct classes of projection neurons. Recent work suggests the cortex may contain intrinsically fate-restricted progenitors marked by expression of Cux2. However, the heterogeneity of the neocortical ventricular zone as well as the contribution of lineage-restricted progenitors to the overall cortical neurogenic program remains unclear. Here, we utilize in vivo genetic fate mapping to demonstrate that Fezf2-expressing radial glial cells (RGCs) exist throughout cortical development and sequentially generate all major projection neuron subtypes and glia. Moreover, we show that the vast majority of CUX2+ cells in the VZ and SVZ are migrating interneurons derived from the subcortical telencephalon. Examination of the embryonic cortical progenitor population demonstrates that Cux2+ RGCs generate both deep- and upper-layer projection neurons. These results identify Fezf2+ radial glial cells as a multipotent neocortical progenitor and suggest that the existence, and molecular identity, of laminar-fate-restricted RGCs awaits further investigation.