UC San Diego

Glutamatergic neurons in the cerebral cortex are derived from embryonic neural stem cells known as radial glial progenitors (RGPs). Early RGPs, present at the onset of cortical neurogenesis, are classically thought to produce columnar clones of glutamatergic neurons spanning the cortical layers. Recently, however, it has been reported that a subset of early RGPs may undergo early commitment to upper layer neuron fates, thus bypassing genesis of deep layer neurons. However, the latter mode of early RGP differentiation was not confirmed in some other studies, and remains controversial. To further investigate the clonal output from early RGPs, we employed genetic lineage tracing driven by Sox9, a transcription factor gene that is expressed in all early RGPs. We found that early RGPs produced columnar clones spanning all cortical layers, with no evidence of significant laminar fate restriction. These data support the classic progressive restriction model of cortical neurogenesis, and suggest that early RGPs do not undergo early commitment to only upper or lower layer fates.