title: Arteriolar and venular patterning in retinas of mice selectively expressing VEGF isoforms.
abstract: 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.
authors.affiliation: The Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Catholic University Leuven, Leuven, Belgium.
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Stalmans
authors.forename: Yin-Shan
authors.initials: YS
authors.lastname: Ng
authors.forename: Richard
authors.initials: R
authors.lastname: Rohan
authors.forename: Marcus
authors.initials: M
authors.lastname: Fruttiger
authors.forename: Ann
authors.initials: A
authors.lastname: Bouché
authors.forename: Ali
authors.initials: A
authors.lastname: Yuce
authors.forename: Hajime
authors.initials: H
authors.lastname: Fujisawa
authors.forename: Bart
authors.initials: B
authors.lastname: Hermans
authors.forename: Moshe
authors.initials: M
authors.lastname: Shani
authors.forename: Sandra
authors.initials: S
authors.lastname: Jansen
authors.forename: Dan
authors.initials: D
authors.lastname: Hicklin
authors.forename: David J
authors.initials: DJ
authors.lastname: Anderson
authors.forename: Tom
authors.initials: T
authors.lastname: Gardiner
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hammes
authors.forename: Lieve
authors.initials: L
authors.lastname: Moons
authors.forename: Mieke
authors.initials: M
authors.lastname: Dewerchin
authors.forename: Désiré
authors.initials: D
authors.lastname: Collen
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
authors.forename: Patricia A
authors.initials: PA
authors.lastname: D'Amore
mesh_terms: 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
chemical_list: 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