Role of subplate neurons in the development and evolution of the mammalian neocortex

In the mammalian neocortex, an enormous number of neurons are precisely arranged in an ordered 6-layered structure in an inside-out manner. This structure is formed by the sequential generation of neurons and their migration toward the brain surface, termed radial neuronal migration. In order to complete the neocortical layer structure within the limited time period of embryogenesis, the radial migration process must be controlled precisely and efficiently. We previously reported that subplate neurons (SpNs), one of the firstborn and matured types of neurons in the developing neocortex, play an important role in regulating radial migration. In addition to controlling radial neuronal migration, the subplate (SP) layer is essential in establishing thalamocortical connections and plays a critical role in embryonic cortex formation. Primates such as monkeys and humans have a transiently highly expanded SP layer during the embryonic period compared to mice. However, its biological significance and the molecular mechanisms responsible for this expansion still need to be understood. We aimed to elucidate the mechanism by performing Visium and Xenium spatial transcriptomic analysis using the embryonic cerebrum of marmosets and humans. By comparing these data with mouse data, we identified genes specifically expressed in the SP layer of the primate. I will discuss the candidate genes identified in this analysis and the role of the SP layer in the evolution of the mammalian brain.