OSVZ progenitors in the human cortex: an updated perspective on neurodevelopmental disease

Recent discoveries concerning the architecture and cellular dynamics of the developing human brain are revealing new differences between mouse and human cortical development. In mice, neurons are produced by ventricular radial glial (RG) cells and subventricular zone intermediate progenitor (IP) cells. In the human cortex, both ventricular RG and highly motile outer RG cells generate IP cells, which undergo multiple rounds of transit amplification in the outer subventricular zone before producing neurons. This creates a more complex environment for neurogenesis and neuronal migration, adding new arenas in which neurodevelopmental disease gene mutation could disrupt corticogenesis. A more complete understanding of disease mechanisms will involve use of emerging model systems with developmental programs more similar to that of the human neocortex.

► Mechanisms of neurodevelopmental diseases have primarily been modeled in the mouse. ► Neurodevelopmental disease genes often impact centrosome and microtubule dynamics. ► Human neocortex development involves a novel lineage of neural stem cells in the OSVZ. ► OSVZ cell behaviors probably also involve the centrosome and microtubule dynamics. ► The role of disease genes in OSVZ development must now be considered.