Regulation of angiogenesis by a non-canonical Wnt-Flt1 pathway in myeloid cells

Nature. 2011 May 29;474(7352):511-5. doi: 10.1038/nature10085.

Abstract

Myeloid cells are a feature of most tissues. Here we show that during development, retinal myeloid cells (RMCs) produce Wnt ligands to regulate blood vessel branching. In the mouse retina, where angiogenesis occurs postnatally, somatic deletion in RMCs of the Wnt ligand transporter Wntless results in increased angiogenesis in the deeper layers. We also show that mutation of Wnt5a and Wnt11 results in increased angiogenesis and that these ligands elicit RMC responses via a non-canonical Wnt pathway. Using cultured myeloid-like cells and RMC somatic deletion of Flt1, we show that an effector of Wnt-dependent suppression of angiogenesis by RMCs is Flt1, a naturally occurring inhibitor of vascular endothelial growth factor (VEGF). These findings indicate that resident myeloid cells can use a non-canonical, Wnt-Flt1 pathway to suppress angiogenic branching.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Vessels / growth & development
  • Endothelial Cells / metabolism
  • Fibroblasts
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • LDL-Receptor Related Proteins / genetics
  • LDL-Receptor Related Proteins / metabolism
  • Ligands
  • Low Density Lipoprotein Receptor-Related Protein-5
  • Mice
  • Myeloid Cells / metabolism*
  • Neovascularization, Physiologic / physiology*
  • Receptors, G-Protein-Coupled
  • Retina / cytology*
  • Signal Transduction*
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor Receptor-1 / deficiency
  • Vascular Endothelial Growth Factor Receptor-1 / genetics
  • Vascular Endothelial Growth Factor Receptor-1 / metabolism*
  • Wnt Proteins / deficiency
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*
  • Wnt-5a Protein

Substances

  • Gpr177 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • LDL-Receptor Related Proteins
  • Ligands
  • Low Density Lipoprotein Receptor-Related Protein-5
  • Lrp5 protein, mouse
  • Receptors, G-Protein-Coupled
  • Vascular Endothelial Growth Factor A
  • Wnt Proteins
  • Wnt-5a Protein
  • Wnt11 protein, mouse
  • Wnt5a protein, mouse
  • Flt1 protein, mouse
  • Vascular Endothelial Growth Factor Receptor-1