β8 integrin is essential for neuroblast migration in the rostral migratory stream

Neurogenesis in the post-natal brain occurs in two primary locations: the subgranular layer of the hippocampal dentate gyrus and the subventricular zone (SVZ) of the lateral ventricles. Following differentiation, neuroblasts within the SVZ migrate several millimeters to the olfactory bulbs (OBs) via a distinct anatomic route, or rostral migratory stream (RMS). The genes that govern neuroblast directional migration, and particularly those encoding cell adhesion and signaling factors, remain largely uncharacterized. Here, we report that the extracellular matrix adhesion receptor, β8 integrin, is essential for proper neuroblast chain formation and directional navigation in the RMS. Primary neuroblasts isolated from the mouse brain express robust levels of β8 integrin protein, and selective ablation of β8 integrin gene expression in neuroblasts leads to aberrant chain migration and size-reduced OBs. These integrin-dependent defects can be recapitulated ex vivo using isolated neurospheres or SVZ explants. Collectively, these data identify essential cell-intrinsic functions for β8 integrin in regulating neuroblast polarity and directional navigation in the mouse forebrain.