Arteriolar and venular patterning in retinas of mice selectively expressing VEGF isoforms.
The murine VEGF gene is alternatively transcribed to yield the VEGF(120), VEGF(164), and VEGF(188) isoforms, which differ in their potential to bind to heparan sulfate and neuropilin-1 and to stimulate endothelial growth. Here, their role in retinal vascular development was studied in mice selectively expressing single isoforms. VEGF(164/164) mice were normal, healthy, and had normal retinal angiogenesis. In contrast, VEGF(120/120) mice exhibited severe defects in vascular outgrowth and patterning, whereas VEGF(188/188) mice displayed normal venular outgrowth but impaired arterial development. It is noteworthy that neuropilin-1, a receptor for VEGF(164), was predominantly expressed in retinal arterioles. These findings reveal distinct roles of the various VEGF isoforms in vascular patterning and arterial development in the retina.
Stalmans
Ingeborg
I
The Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Catholic University Leuven, Leuven, Belgium.
Ng
Yin-Shan
YS
Rohan
Richard
R
Fruttiger
Marcus
M
Bouché
Ann
A
Yuce
Ali
A
Fujisawa
Hajime
H
Hermans
Bart
B
Shani
Moshe
M
Jansen
Sandra
S
Hicklin
Dan
D
Anderson
David J
DJ
Gardiner
Tom
T
Hammes
Hans-Peter
HP
Moons
Lieve
L
Dewerchin
Mieke
M
Collen
Désiré
D
Carmeliet
Peter
P
D'Amore
Patricia A
PA
D000818:Animals; D001160:Arterioles / Q000002:abnormalities / Q000254:growth & development; D001483:Base Sequence; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D004247:DNA / Q000235:genetics; D016228:Endothelial Growth Factors / Q000235:genetics* / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D008222:Lymphokines / Q000235:genetics* / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011247:Pregnancy; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D017978:Receptors, Growth Factor / Q000235:genetics; D040262:Receptors, Vascular Endothelial Growth Factor; D012171:Retinal Vessels / Q000002:abnormalities / Q000254:growth & development*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014699:Venules / Q000002:abnormalities / Q000254:growth & development
D016228:Endothelial Growth Factors; D008222:Lymphokines; D020033:Protein Isoforms; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D004247:DNA; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor