Sox5 specifies layer V subcerebral versus callosal projection neuronal fates

The precise generation of distinct subtypes of neocortical projection neurons and their proper migration into appropriate laminar positions underlies our most advanced cognitive and perceptual abilities. Recent work suggests that a transcription factor network, including the genes Sox5, Satb2, Fezf2, and Bcl11b, is responsible for directing the fate specification of subcerebral projection neurons (SCPN) in layer Vb of the cerebral cortex, which is immediately adjacent to laver Va, which is comprised of callosal projection neurons (CPN). Because we observed the absence of SCPN in Sox5 null cortices, we hypothesized that Sox5 may specify subcerebral versus callosal neuronal fates in layer V of the cortex. Here, via a series of in situ hybridization and immunohistochemistry, and retrograde tracing experiments, we show that in Sox5 null cortices, layer V neurons do not take on the molecular identity of layer Vb SCPN and instead, they appear to take on the identity of layer Va CPN. I also demonstrate via birthdating experiments that there is a migration defect Sox5 null cortices, and layer V cells are generated prematurely. Overall, the work presented here provides an in-depth phenotypical characterization of layer V in Sox5 null cortices