Vascular development of the brain requires β8 integrin expression in the neuroepithelium

We showed previously that loss of the integrin beta 8 subunit, which forms alpha v beta 8 heterodimers, results in abnormal vascular development in the yolk sac, placenta, and brain. Animals lacking the integrin beta 8 (itg beta 8) gene die either at midgestation, because of insufficient vascularization of the placenta and yolk sac, or shortly after birth with severe intracerebral hemorrhage. To specifically focus on the role of integrins containing the beta 8 subunit in the brain, and to avoid early lethalities, we used a targeted deletion strategy to delete itg beta 8 only from cell types within the brain. Ablating itg beta 8 from vascular endothelial cells or from migrating neurons did not result in cerebral hemorrhage. Targeted deletion of itg beta 8 from the neuroepithelium, however, resulted in bilateral hemorrhage at postnatal day 0, although the phenotype was less severe than in itg beta 8-null animals. Newborn mice lacking itg beta 8 from the neuroepithelium had hemorrhages in the cortex, ganglionic eminence, and thalamus, as well as abnormal vascular morphogenesis, and disorganized glia. Interestingly, adult mice lacking itg beta 8 from cells derived from the neuroepithelium did not show signs of hemorrhage. We propose that defective association between vascular endothelial cells and glia lacking itg beta 8 is responsible for the leaky vasculature seen during development but that an unidentified compensatory mechanism repairs the vasculature after birth.