ZFIN ID: ZDB-PUB-050920-14
Vascular endothelial growth factor receptor signaling is required for cardiac valve formation in zebrafish
Lee, Y.M., Cope, J.J., Ackermann, G.E., Goishi, K., Armstrong, E.J., Paw, B.H., and Bischoff, J.
Date: 2006
Source: Developmental dynamics : an official publication of the American Association of Anatomists   235(1): 29-37 (Journal)
Registered Authors: Ackermann, Gabriele, Cope, John, Goishi, Katsutoshi, Paw, Barry
Keywords: VEGF receptors, cardiac valves, endothelium, NFAT, zebrafish
MeSH Terms:
  • 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
PubMed: 16170785 Full text @ Dev. Dyn.
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.