UCSF

The evolutionary expansion of the mammalian cerebral cortex is responsible for our unique higher cognitive abilities such as language and conscious thought. Developmental changes in neural progenitor composition likely contributed to the increased size and number of neurons in the primate cortex. For instance, a germinal region, referred to as the subventricular zone (SVZ), is greatly expanded in primates and contains a heterogeneous population of neural progenitors, including outer radial glia (oRGs). Since oRGs are more abundant in the primate than the rodent and contribute to neurogenesis, an increase in this cell population is thought to underlie cortical expansion and folding. However, the specific contribution of oRGs and other cell populations, such as neurons, to the size and shape of the adult mammalian cortex remains unknown. Since the ferret is gyrencephalic, possesses an enlarged SVZ with an abundance of oRGs, and is experimentally tractable, it provides an attractive model for studying cortical expansion and folding. Here, I provide a detailed characterization of progenitor and migrating neuron behaviors in the developing ferret cortex. I present data demonstrating the mitotic behaviors, proliferative capacity, and daughter cell fates of ferret oRGs and highlight morphological diversity within this progenitor population. I go on to present a technique for visualizing neurogenic divisions and neuronal migration in the ferret cortex. I describe neuronal migration properties that appear to differ from the rodent, such as greater variation in the direction of migration and increased meandering, specifically at later ages when the ferret cortex has begun to fold. These data provide a framework for future studies using the ferret to elucidate the cellular and molecular mechanisms of cortical expansion and folding, as well as neurodevelopmental diseases.