Abundant Self-Amplifying Intermediate Progenitors in the Subventricular Zone of the Chinese Tree Shrew Neocortex

During evolution, neural progenitor cells in the subventricular zone (SVZ) have fundamental functions, ranging from brain volume expansion to the generation of a six-layered neocortex. In lissencephalic animal models, such as rodents, the majority of neural progenitors in the SVZ are intermediate progenitor cells (IPCs). Most IPCs in rodents undergo neurogenic division, and only a small portion of them divide a very limited number of times to generate a few neurons. Meanwhile, in gyrencephalic animals, such as primates, IPCs are able to self-renew for up to five successive divisions. However, abundant IPCs with successive proliferative capacity have not been directly observed in nonprimate species. In this study, we examined the development of neural progenitors in the Chinese tree shrew (Tupaia belangeri chinensis), a lissencephalic animal with closer affinity than rodents to primates. We identified an expansion of the SVZ and the presence of outer radial glial (oRG) cells in the neocortex. We also found that IPCs have the capacity to self-amplify multiple times and therefore serve as major proliferative progenitors. To our knowledge, our study provides the first direct evidence of abundant IPCs with proliferative potential in a nonprimate species, further supporting the key role of IPCs in brain expansion.