Neuropilin 1 balances 8 integrin-activated TGF signaling to control sprouting angiogenesis in the brain. Academic Article uri icon

abstract

  • 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 8 integrin (Itgb8) and neuropilin1 (Nrp1) cooperatively promote CNS angiogenesis by mediating adhesion and signaling events between neuroepithelial cells and vascular endothelial cells. 8 integrin in the neuroepithelium promotes the activation of extracellular matrix (ECM)-bound latent transforming growth factor (TGF) ligands and stimulates TGF receptor signaling in endothelial cells. Nrp1 in endothelial cells suppresses TGF activation and signaling by forming intercellular protein complexes with 8 integrin. Cell type-specific ablation of 8 integrin, Nrp1, or canonical TGF receptors results in pathological angiogenesis caused by defective neuroepithelial cell-endothelial cell adhesion and imbalances in canonical TGF signaling. Collectively, these data identify a paracrine signaling pathway that links the neuroepithelium to blood vessels and precisely balances TGF signaling during cerebral angiogenesis.

published proceedings

  • Development

altmetric score

  • 3.75

author list (cited authors)

  • Hirota, S., Clements, T. P., Tang, L. K., Morales, J. E., Lee, H. S., Oh, S. P., ... McCarty, J. H.

citation count

  • 56

complete list of authors

  • Hirota, Shinya||Clements, Thomas P||Tang, Leung K||Morales, John E||Lee, Hye Shin||Oh, S Paul||Rivera, Gonzalo M||Wagner, Daniel S||McCarty, Joseph H

publication date

  • December 2015