Neuropilin-1 balances β8 integrin-activated TGFβ signaling to control sprouting angiogenesis in the brain
Citations Over TimeTop 10% of 2015 papers
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 β8 integrin (Itgb8) and neuropilin 1 (Nrp1) cooperatively promote CNS angiogenesis by mediating adhesion and signaling events between neuroepithelial cells and vascular endothelial cells. β8 integrin in the neuroepithelium promotes the activation of extracellular matrix (ECM)-bound latent transforming growth factor β (TGFβ) ligands and stimulates TGFβ receptor signaling in endothelial cells. Nrp1 in endothelial cells suppresses TGFβ activation and signaling by forming intercellular protein complexes with β8 integrin. Cell type-specific ablation of β8 integrin, Nrp1, or canonical TGFβ receptors results in pathological angiogenesis caused by defective neuroepithelial cell-endothelial cell adhesion and imbalances in canonical TGFβ signaling. Collectively, these data identify a paracrine signaling pathway that links the neuroepithelium to blood vessels and precisely balances TGFβ signaling during cerebral angiogenesis.
Related Papers
- → Inhibition of both paracrine and autocrine VEGF/ VEGFR-2 signaling pathways is essential to induce long-term remission of xenotransplanted human leukemias(2001)269 cited
- → Computational model and microfluidic platform for the investigation of paracrine and autocrine signaling in mouse embryonic stem cells(2009)40 cited
- → Renal Autocrine and Paracrine Signaling: A Story of Self-protection(2020)27 cited
- → Autocrine/Paracrine Function of Parathyroid Hormone-Related Peptide in Rat Osteoblast-like Cells(1993)16 cited
- The possible role of IL—1 autocrine and paracrine in mesangial cell(MSc)(1992)