Integrin-Mediated Adhesion and Signaling in the Neurovascular Niche

Neural progenitors (NPs) in the central nervous system (CNS) reside in a neurovascular niche. Cell‐cell and cell‐extracellular matrix interactions within the neurovascular niche regulate NP self‐renewal and differentiation; however, the mechanisms used by NPs to communicate with blood vessels remain largely uncharacterized. We have shown previously that genetic ablation of αvβ8 integrin expression in NPs leads to profound neurovascular phenotypes due to defective cell‐ECM adhesion in the neurovascular niche. Here, we have analyzed αvβ8 integrin in NPs purified from wild type or αv and β8 integrin knockout (KO) mice. Cells lacking αvβ8 integrin display reduced self‐renewal, as assayed by neurosphere formation. Furthermore, αvβ8 KO cells display preferential differentiation toward the astroglial lineage following serum exposure. Subventricular zone NPs in adult β8 integrin KO mice show reduced self‐renewal, which is associated with abnormal SVZ ultrastructure. KO mice also develop size‐reduced olfactory bulbs, indicative of impaired NP growth and differentiation. Our various data for αvβ8 integrin are very similar to results for a regulator of NP self‐renewal, Bmi1. Indeed, our data mining efforts reveal that Bmi1 regulates αvβ8 integrin gene expression. Collectively, these studies identify essential roles for αvβ8 integrin in NP self‐renewal and differentiation in the CNS neurovascular niche.