Elevated vascular endothelial cell growth factor affects mesocardial morphogenesis and inhibits normal heart bending.
Signaling by means of vascular endothelial cell growth factor (VEGF) and its receptors (VEGFRs) is required for cardiovascular development. To examine how VEGF/VEGFR receptor signaling affects early endocardial cell behavior, embryonic quail hearts were subjected to elevated VEGF165 levels (five- to nine-somite stage). Primitive embryonic hearts microinjected with recombinant human (rh)VEGF165 exhibit several distinct malformations compared with hearts in untreated embryos: the endocardial tube is malformed with tortuous cords and folds surrounded by a diminished cardiac jelly space, and the lumens of affected hearts are conspicuously reduced. Furthermore, the embryonic heart fails to loop properly. Inhibition of bending is accompanied by an apparent failure of the dorsal mesocardium to atrophy--an event thought to be necessary for heart bending. Instead of atrophy, VEGF-treated mesocardia exhibit a marked increased in the number of resident endothelial cells. Collectively, the data suggest that the abnormally robust mesocardia in VEGF-treated hearts impede the mechanical deformation required for normal heart bending. We conclude that the excessive VEGF signaling culminates in a physical or biomechanical mechanism that acts over a wide, tissue-level, length scale to cause a severe developmental defect--failure of heart bending.
Drake
Christopher J
CJ
Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, South Carolina, USA.
Wessels
Andy
A
Trusk
Tom
T
Little
Charles D
CD
D000818:Animals; D001284:Atrophy; D004625:Embryo, Nonmammalian; D004699:Endocardium / Q000196:embryology; D006321:Heart / Q000196:embryology*; D006330:Heart Defects, Congenital / Q000196:embryology* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008643:Mesentery / Q000196:embryology* / Q000473:pathology; D009206:Myocardium / Q000473:pathology*; D011784:Quail / Q000196:embryology*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000502:physiology; D011994:Recombinant Proteins / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology
D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor