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PMID:16170785
| Citation |
Lee, YM, Cope, JJ, Ackermann, GE, Goishi, K, Armstrong, EJ, Paw, BH and Bischoff, J (2006) Vascular endothelial growth factor receptor signaling is required for cardiac valve formation in zebrafish. Dev. Dyn. 235:29-37 |
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| Abstract |
Vascular endothelial growth factor-receptors (VEGF-Rs) are pivotal regulators of vascular development, but a specific role for these receptors in the formation of heart valves has not been identified. We took advantage of small molecule inhibitors of VEGF-R signaling and showed that blocking VEGF-R signaling with receptor selective tyrosine kinase inhibitors, PTK 787 and AAC 787, from 17-21 hr post-fertilization (hpf) in zebrafish embryos resulted in a functional and structural defect in cardiac valve development. Regurgitation of blood between the two chambers of the heart, as well as a loss of cell-restricted expression of the valve differentiation markers notch 1b and bone morphogenetic protein-4 (bmp-4), was readily apparent in treated embryos. In addition, microangiography revealed a loss of a definitive atrioventricular constriction in treated embryos. Taken together, these data demonstrate a novel function for VEGF-Rs in the endocardial endothelium of the developing cardiac valve. |
| Links |
PubMed PMC2811314 Online version:10.1002/dvdy.20559 |
| Keywords |
Animals; Bone Morphogenetic Protein 4; Bone Morphogenetic Proteins/biosynthesis; Bone Morphogenetic Proteins/genetics; Cell Nucleus/metabolism; Cells, Cultured; Gene Expression Regulation, Developmental/drug effects; Heart Valves/abnormalities; Heart Valves/drug effects; Heart Valves/embryology; Heart Valves/physiology; Humans; NFATC Transcription Factors/metabolism; Phthalazines/pharmacology; Pyridines/pharmacology; Receptor, Notch1/biosynthesis; Receptor, Notch1/genetics; Receptors, Vascular Endothelial Growth Factor/physiology; Signal Transduction/drug effects; Signal Transduction/physiology; Zebrafish/embryology; Zebrafish/physiology; Zebrafish Proteins |
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