Role of VEGF and tissue hypoxia in patterning of neural and vascular cells recruited to the embryonic heart.
We hypothesized that oxygen gradients and hypoxia-responsive signaling may play a role in the patterning of neural or vascular cells recruited to the developing heart. Endothelial progenitor and neural cells are recruited to and form branched structures adjacent to the relatively hypoxic outflow tract (OFT) myocardium from stages 27-32 (ED6.5-7.5) of chick development. As determined by whole mount confocal microscopy, the neural and vascular structures were not anatomically associated. Adenoviral delivery of a VEGF trap dramatically affected the remodeling of the vascular plexus into a coronary tree while neuronal branching was normal. Both neuronal and vascular branching was diminished in the hearts of embryos incubated under hyperoxic conditions. Quantitative analysis of the vascular defects using our recently developed VESGEN program demonstrated reduced small vessel branching and increased vessel diameters. We propose that vascular and neural patterning in the developing heart share dependence on tissue oxygen gradients but are not interdependent.
Department of Medicine (Cardiology), Case Western Reserve University, Cleveland, Ohio 44106, USA.
Hongbin
H
Liu
Qiwei
Q
Yang
Krishnan
K
Radhakrishnan
Dedra E
DE
Whitfield
Camille L M
CL
Everhart
Patricia
P
Parsons-Wingerter
Steven A
SA
Fisher
D000818:Animals; D004625:Embryo, Nonmammalian / Q000196:embryology* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006321:Heart / Q000196:embryology* / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000502:physiology; D009415:Nerve Net / Q000196:embryology* / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology; D010100:Oxygen / Q000378:metabolism*; D011784:Quail; D014162:Transfection; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism*; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism*
D042442:Vascular Endothelial Growth Factors; D040301:Vascular Endothelial Growth Factor Receptor-2; D010100:Oxygen