Development of the mouse retinal vasculature: angiogenesis versus vasculogenesis.
OBJECTIVE
The inner vasculature of the retina develops as a spreading network, which is preceded by spindle-shaped cells. These cells are alleged to be vascular precursor cells (angioblasts). This study was designed to test whether such angioblasts exist in neonatal mouse retina.


METHODS
In situ hybridization and immunohistochemistry on mouse retinal wholemount preparations were used to visualize specific vascular cell types.


RESULTS
In situ hybridization with an RNA probe against vascular endothelial growth factor receptor (VEGFR)-2 (a marker for endothelial cells and angioblasts) labeled the vascular network but failed to label the spindle-shaped cells in front of it. A probe against VEGFR1, a marker for endothelial cells only, revealed the same staining pattern. Pericytes, visualized with a probe against platelet-derived growth receptor (PDGFR)-beta, were spread over the entire vessel network, but not beyond it. However, in situ hybridization with a probe against PDGFRalpha (a marker for retinal astrocytes) labeled spindle-shaped cells preceding the vessel network.


CONCLUSIONS
These observations imply that in the mouse retina the spindle-shaped cells preceding the forming vasculature are immature retinal astrocytes and not vascular precursor cells and that the primary vascular network in the retina develops by angiogenesis (budding from existing vessels) and not vasculogenesis (assembly of dispersed angioblasts).
Fruttiger
Marcus
M
Wolfson Institute for Biomedical Research, University College London, United Kingdom. m.fruttiger@ucl.ac.uk
D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D017403:In Situ Hybridization; D051379:Mice; D009024:Morphogenesis; D018919:Neovascularization, Physiologic; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D015347:RNA Probes; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor; D012171:Retinal Vessels / Q000254:growth & development* / Q000502:physiology; D040281:Vascular Endothelial Growth Factor Receptor-1
D011518:Proto-Oncogene Proteins; D015347:RNA Probes; D017978:Receptors, Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1