| First Author | Hirota S | Year | 2015 |
| Journal | Development | Volume | 142 |
| Issue | 24 | Pages | 4363-73 |
| PubMed ID | 26586223 | Mgi Jnum | J:240012 |
| Mgi Id | MGI:5882189 | Doi | 10.1242/dev.113746 |
| Citation | Hirota S, et al. (2015) Neuropilin 1 balances beta8 integrin-activated TGFbeta signaling to control sprouting angiogenesis in the brain. Development 142(24):4363-73 |
| abstractText | Angiogenesis in the developing central nervous system (CNS) is regulated by neuroepithelial cells, although the genes and pathways that couple these cells to blood vessels remain largely uncharacterized. Here, we have used biochemical, cell biological and molecular genetic approaches to demonstrate that beta8 integrin (Itgb8) and neuropilin 1 (Nrp1) cooperatively promote CNS angiogenesis by mediating adhesion and signaling events between neuroepithelial cells and vascular endothelial cells. beta8 integrin in the neuroepithelium promotes the activation of extracellular matrix (ECM)-bound latent transforming growth factor beta (TGFbeta) ligands and stimulates TGFbeta receptor signaling in endothelial cells. Nrp1 in endothelial cells suppresses TGFbeta activation and signaling by forming intercellular protein complexes with beta8 integrin. Cell type-specific ablation of beta8 integrin, Nrp1, or canonical TGFbeta receptors results in pathological angiogenesis caused by defective neuroepithelial cell-endothelial cell adhesion and imbalances in canonical TGFbeta signaling. Collectively, these data identify a paracrine signaling pathway that links the neuroepithelium to blood vessels and precisely balances TGFbeta signaling during cerebral angiogenesis. |
