PUBLICATION

Inhibition of zebrafish epidermal growth factor receptor activity results in cardiovascular defects

Authors
Goishi, K., Lee, P., Davidson, A.J., Nishi, E., Zon, L.I., Klagsbrun, M.
ID
ZDB-PUB-030826-21
Date
2003
Source
Mechanisms of Development   120(7): 811-822 (Journal)
Registered Authors
Davidson, Alan, Goishi, Katsutoshi, Zon, Leonard I.
Keywords
none
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Cardiovascular Abnormalities/etiology
  • Cardiovascular Abnormalities/metabolism*
  • Humans
  • Molecular Sequence Data
  • Pyrimidines/pharmacology
  • Pyrroles/pharmacology
  • Quinazolines
  • Rats
  • Tyrphostins/pharmacology
  • Zebrafish/embryology*
  • Zebrafish/metabolism
PubMed
12915231 Full text @ Mech. Dev.
Abstract
The physiological role of any of the epidermal growth factor (EGF) receptor tyrosine kinases has yet to be determined in zebrafish. We isolated a zebrafish homologue of EGFR (egfr) that shows a 63% amino acid overall identity to human EGFR but with 90% amino acid identity in the kinase domain. Whole mount in situ hybridization showed ubiquitous distribution of egfr transcripts during gastrulation, somitogenesis and later stages. When expressed in Chinese hamster ovary cells, zebrafish Egfr was a functional receptor that responded to EGF by receptor tyrosine phosphorylation and activation of MAP kinase. The function of zebrafish Egfr in vivo was determined by inhibiting its activity using EGFR kinase inhibitors and antisense morpholinos (MO), which inhibited Egfr kinase activity and translation of egfr messenger RNA into protein, respectively. The zebrafish is a particularly excellent model for studying cardiovascular development because zebrafish are transparent allowing direct visualization of the heart and circulation in the blood vessels. Inhibition of zebrafish Egfr activity in vivo impeded blood flow via the outflow tract into the aorta and impeded circulation in the axial and intersegmental vessels by 80 h post-fertilization. Analysis of the heart showed that the heart chambers and pericardial sacs were dilated and the outflow tracts were narrowed. Together these results suggested that zebrafish Egfr has a cardiovascular function in the developing zebrafish that is required for normal circulation.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping