PUBLICATION

Neuropilin 1 balances β8 integrin-activated TGFβ signaling to control sprouting angiogenesis in the brain

Authors
Hirota, S., Clements, T.P., Tang, L.K., Morales, J.E., Lee, H.S., Oh, S.P., Rivera, G.M., Wagner, D.S., McCarty, J.H.
ID
ZDB-PUB-170214-76
Date
2015
Source
Development (Cambridge, England)   142: 4363-73 (Journal)
Registered Authors
Wagner, Daniel
Keywords
Endothelial cell, Extracellular matrix, Neurovascular unit, itgb8, nrp1, tgfbr2
MeSH Terms
  • Animals
  • Models, Biological
  • Signal Transduction*
  • Integrin beta Chains/metabolism*
  • Endothelial Cells/cytology
  • Endothelial Cells/metabolism
  • Gene Deletion
  • Neuropilin-1/metabolism*
  • Embryo Loss/pathology
  • Actins/metabolism
  • Neuroepithelial Cells/cytology
  • Neuroepithelial Cells/metabolism
  • Transforming Growth Factor beta/metabolism*
  • Zebrafish
  • Cell Adhesion
  • Brain/blood supply*
  • Brain/metabolism*
  • Brain/pathology
  • Neovascularization, Physiologic*
  • Mice
  • Male
(all 21)
PubMed
26586223 Full text @ Development
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.
Genes / Markers
Figures
Figure Gallery (1 images)
Show all Figures
Expression
Phenotype
Mutations / Transgenics
No data available
Human Disease / Model
No data available
Sequence Targeting Reagents
Target Reagent Reagent Type
itgb8MO1-itgb8MRPHLNO
itgb8MO3-itgb8MRPHLNO
nrp1aMO2-nrp1aMRPHLNO
nrp1aMO8-nrp1aMRPHLNO
tp53MO4-tp53MRPHLNO
1 - 5 of 5
Show
Fish
Antibodies
No data available
Orthology
No data available
Engineered Foreign Genes
No data available
Mapping
No data available