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

• Published in: Neuron (Cambridge, Mass.) Mass.), 2013-12, Vol.80 (5), p.1167-1174
• Main Authors: Guo, Chao, Eckler, Matthew J., McKenna, William L., McKinsey, Gabriel L., Rubenstein, John L.R., Chen, Bin
• Format: Article
• Language: English
• Subjects: Age Factors; Animals; Animals, Newborn; Artificial chromosomes; Astrocytes - metabolism; Cell Differentiation; Cell Movement - genetics; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Embryo, Mammalian; Endopeptidases - genetics; Endopeptidases - metabolism; Experiments; Functional Laterality; Gene expression; Gene Expression Regulation, Developmental - physiology; Green Fluorescent Proteins - genetics; Homeodomain Proteins - genetics; Hybridization; Mice; Mice, Transgenic; Multipotent Stem Cells - physiology; Neocortex - cytology; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurons; Neurons - metabolism; Oligodendroglia - metabolism; Proteins; Transcription Factors - metabolism
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2013.09.037

Progenitor 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. •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 Guo et al. describe in vivo lineage tracing experiments in the developing neocortex. These results demonstrate that expression of Fezf2 marks progenitor cells that sequentially generate projection neurons and glia, consistent with the progressive lineage restriction model of cortical neurogenesis.