PUBLICATION
Vascular endothelial growth factor receptor signaling is required for cardiac valve formation in zebrafish
- Authors
- Lee, Y.M., Cope, J.J., Ackermann, G.E., Goishi, K., Armstrong, E.J., Paw, B.H., and Bischoff, J.
- ID
- ZDB-PUB-050920-14
- 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.
Citation
Lee, Y.M., Cope, J.J., Ackermann, G.E., Goishi, K., Armstrong, E.J., Paw, B.H., and Bischoff, J. (2006) Vascular endothelial growth factor receptor signaling is required for cardiac valve formation in zebrafish. Developmental Dynamics : an official publication of the American Association of Anatomists. 235(1):29-37.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping