Evolutionary origin of Tbr2-expressing precursor cells and the subventricular zone in the developing cortex

The subventricular zone (SVZ) is greatly expanded in primates with gyrencephalic cortices and is thought to be absent from vertebrates with three-layered, lissencephalic cortices, such as the turtle. Recent work in rodents has shown that Tbr2-expressing neural precursor cells in the SVZ produce excitatory neurons for each cortical layer in the neocortex. Many excitatory neurons are generated through a two-step process in which Pax6-expressing radial glial cells divide in the VZ to produce Tbr2-expressing intermediate progenitor cells, which divide in the SVZ to produce cortical neurons. We investigated the evolutionary origin of SVZ neural precursor cells in the prenatal cerebral cortex by testing for the presence and distribution of Tbr2-expressing cells in the prenatal cortex of reptilian and avian species. We found that mitotic Tbr2⁺ cells are present in the prenatal cortex of lizard, turtle, chicken, and dove. Furthermore, Tbr2⁺ cells are organized into a distinct SVZ in the dorsal ventricular ridge (DVR) of turtle forebrain and in the cortices of chicken and dove. Our results are consistent with the concept that Tbr2⁺ neural precursor cells were present in the common ancestor of mammals and reptiles. Our data also suggest that the organizing principle guiding the assembly of Tbr2⁺ cells into an anatomically distinct SVZ, both developmentally and evolutionarily, may be shared across vertebrates. Finally, our results indicate that Tbr2 expression can be used to test for the presence of a distinct SVZ and to define the boundaries of the SVZ in developing cortices.