| First Author | De A | Year | 2022 |
| Journal | Development | Volume | 149 |
| Issue | 6 | PubMed ID | 35217866 |
| Mgi Jnum | J:321982 | Mgi Id | MGI:7254943 |
| Doi | 10.1242/dev.200472 | Citation | De A, et al. (2022) The beta8 integrin cytoplasmic domain activates extracellular matrix adhesion to promote brain neurovascular development. Development 149(6):dev200472 |
| abstractText | In the developing mammalian brain, neuroepithelial cells interact with blood vessels to regulate angiogenesis, blood-brain barrier maturation and other key neurovascular functions. Genetic studies in mice have shown that neurovascular development is controlled, in part, by Itgb8, which encodes the neuroepithelial cell-expressed integrin beta8 subunit. However, these studies have involved complete loss-of-function Itgb8 mutations, and have not discerned the relative roles for the beta8 integrin extracellular matrix (ECM) binding region versus the intracellular signaling tail. Here, Cre/lox strategies have been employed to selectively delete the cytoplasmic tail of murine Itgb8 without perturbing its transmembrane and extracellular domains. We report that the beta8 integrin cytoplasmic domain is essential for inside-out modulation of adhesion, including activation of latent-TGFbetas in the ECM. Quantitative sequencing of the brain endothelial cell transcriptome identifies TGFbeta-regulated genes with putative links to blood vessel morphogenesis, including several genes linked to Wnt/beta-catenin signaling. These results reveal that the beta8 integrin cytoplasmic domain is essential for the regulation of TGFbeta-dependent gene expression in endothelial cells and suggest that cross-talk between TGFbetas and Wnt pathways is crucial for neurovascular development. |
