Cell Adhesion and Signaling Pathways in Neurovascular Development

Abstract

Precise regulation of cell‐extracellular matrix (ECM) adhesion and communication is essential for development of the neurovascular unit and blood‐brain barrier (BBB). Integrins are receptors for ECM proteins and many integrins are expressed in neural and vascular cells; however, their roles in neurovascular unit development remain mostly uncharacterized. We have analyzed roles for the integrin αvβ8, which is expressed in glial cells where is binds to the ECM‐associated forms of latent TGFβs. Ablation of αv or β8 integrin genes in glial cells leads to vascular pathologies, including abnormal angiogenesis, hemorrhage and premature death associated with neurological decline. Interestingly, when integrin gene expression is inducibly ablated in glial cells of the post‐natal brain, when endothelial cells are no longer actively proliferating and sprouting, we do not detect acute vascular pathologies. However, when we activate pathological angiogenesis in the brain by tumor implantation or vascular damage via cortical stab wounds, αvβ8 integrin is essential for blood vessel growth and BBB permeability. These data reveal essential roles for αvβ8 integrin and its latent TGFβ ligands in regulating neurovascular and BBB development.