Crucial Roles of the Arp2/3 Complex during Mammalian Corticogenesis

Abstract

The polarity and organization of radial glial cells (RGCs), which serve as both stem cells and scaffolds for neuronal migration, are crucial for cortical development. However, the cytoskeletal mechanisms that drive radial glial outgrowth and maintain RGC polarity remain poorly understood. Here, we show that the Arp2/3 complex, the unique actin nucleator that produces branched actin networks, plays essential roles in RGC polarity and morphogenesis. Disruption of the Arp2/3 complex in RGCs retards process outgrowth toward the basal surface and impairs apical polarity and adherens junctions. Whereas the former is correlated with abnormal actin-based leading edge, the latter is consistent with blockage in membrane trafficking. These defects result in altered cell fate, disrupted cortical lamination and abnormal angiogenesis. In addition, we present evidence that the Arp2/3 complex is a cell-autonomous regulator of neuronal migration. Our data suggest that Arp2/3-mediated actin assembly may be particularly important for neuronal cell motility in soft or poorly adhesive matrix environment.