ZFIN ID: ZDB-PUB-100427-3
Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction
Fantin, A., Vieira, J.M., Gestri, G., Denti, L., Schwarz, Q., Prykhozhij, S., Peri, F., Wilson, S.W., and Ruhrberg, C.
Date: 2010
Source: Blood   116(5): 829-840 (Journal)
Registered Authors: Gestri, Gaia, Peri, Francesca, Wilson, Steve
Keywords: none
MeSH Terms:
  • Animals
  • Cell Polarity
  • Endothelial Cells/drug effects
  • Endothelial Cells/physiology
  • Endothelial Cells/ultrastructure
  • Endothelium, Vascular/growth & development
  • Female
  • Gene Knock-In Techniques
  • Macrophage Colony-Stimulating Factor/deficiency
  • Macrophage Colony-Stimulating Factor/genetics
  • Macrophage Colony-Stimulating Factor/physiology
  • Macrophages/physiology*
  • Male
  • Mice
  • Mice, Knockout
  • Neovascularization, Physiologic/drug effects*
  • Neovascularization, Physiologic/physiology
  • Neuropilin-1/physiology
  • Proto-Oncogene Proteins/deficiency
  • Receptor Protein-Tyrosine Kinases/physiology
  • Receptor, TIE-2
  • Retinal Vessels/growth & development
  • Rhombencephalon/blood supply*
  • Rhombencephalon/embryology
  • Trans-Activators/deficiency
  • Vascular Endothelial Growth Factor A/deficiency
  • Vascular Endothelial Growth Factor A/genetics
  • Vascular Endothelial Growth Factor A/physiology*
  • Yolk Sac/cytology
  • Zebrafish/embryology
PubMed: 20404134 Full text @ Blood
FIGURES
ABSTRACT
Blood vessel networks expand in a two-step process that begins with vessel sprouting and is followed by vessel anastomosis. Vessel sprouting is induced by chemotactic gradients of the vascular endothelial growth factor VEGF, which stimulates tip cell protrusion. Yet, it is not known which factors promote the fusion of neighbouring tip cells to add new circuits to the existing vessel network. By combining the analysis of mouse mutants defective in macrophage development or VEGF signalling with live imaging in zebrafish, we now show that macrophages promote tip cell fusion downstream of VEGF-mediated tip cell induction. Macrophages therefore play a hitherto unidentified and unexpected role as vascular fusion cells. Moreover, we show that there are striking molecular similarities between the pro-angiogenic tissue macrophages essential for vascular development and those that promote the angiogenic switch in cancer, including the expression of the cell surface proteins TIE2 and NRP1. Our findings suggest that tissue macrophages are a target for anti-angiogenic therapies, but that they could equally well be exploited to stimulate tissue vascularisation in ischemic disease.
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