Tbr1 regulates differentiation of the preplate and layer 6

During corticogenesis, early-born neurons of the pre-plate and layer 6 are important for guiding subsequent neuronal migrations and axonal projections . Tbr1 is a putative transcription factor that is highly expressed in gluta matergic early-born cortical neurons. In Tbr1-deficient mice, these early-b orn neurons had molecular and functional defects. Cajal-Retzius cells expre ssed decreased levels of Reelin, resulting in a reeler-like cortical migrat ion disorder. Impaired subplate differentiation was associated with ectopic projection of thalamocortical fibers into the basal telencephalon. Layer 6 defects contributed to errors in the thalamocortical, corticothalamic, and callosal projections. These results show that Tbr1 is a common genetic det erminant for the differentiation of early-born glutamatergic neocortical ne urons and provide insights into the functions of these neurons as regulator s of cortical development.