Inhibition of zebrafish epidermal growth factor receptor activity results in cardiovascular defects
Open accessAbstract
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.
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Human recombinant HB-EGF can activate the zebrafish EGFR.
“its ability to activate the zebrafish EGFR”
From HB-EGF is Necessary and Sufficient for Müller Glia Dedifferentiation and Retina Regeneration (2012) · cites this paper as Goishi et al., 2003
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Plexina4 and cell survival in the developing zebrafish hindbrain
Nurcombe, Z. W., Hehr, C. L., & McFarlane, S. (2023) · Developmental Dynamics · doi:10.1002/dvdy.633 · Cited by 2 · see citing works
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Haploinsufficient maternal effect of Epidermal Growth Factor Receptor A mutation in zebrafishPreprint
Ciano, M., Kemp, P. R., Sathyapala, S. A., & Hughes, S. M. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/745018 · Cited by 1 · see citing works
Novel Functions of ErbB4 and NRG-1 in Development and Cancer
Paatero, I. (2013) · UTUPub (University of Turku)
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EGFR confers exquisite specificity of Wnt9a-Fzd9b signaling in hematopoietic stem cell developmentPreprint
Grainger, S. J., Nguyen, N. A., Richter, J., Setayesh, J., Lonquich, B., Oon, C. H., Wozniak, J. M., Barahona, R. A., Kamei, C. N., Houston, J., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/387043
Cardiac Development: Molecular and Genetic Analysis
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- Authors
- Goishi, K., Lee, P., Davidson, A. J., Nishi, E., Zon, L. I., & Klagsbrun, M.
- Affiliations
- Asahikawa Medical College Hospital (JP)
- Boston Children's Hospital (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Klagsbrun, Michael
- Venue
- Mechanisms of Development
- Publisher
- Elsevier BV
- Published
- 2003-07
- Volume
- 120
- Issue
- 7
- Pages
- 811-822
- ISSN
- 0925-4773 (ISSN-L)
- OpenAlex
- W2059513313
- Cited by
- 70
- References
- 43
- Citations by year
- 2024: 1 · 2023: 2 · 2022: 1 · 2021: 4 · 2020: 1 · 2019: 4 · 2018: 5 · 2017: 2 · 2016: 6 · 2015: 3 · 2014: 2 · 2013: 5 · 2012: 4
- FWCI
- 1.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Mechanisms of Development (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (DK49216)
- National Heart, Lung, and Blood Institute (HL 48801, R01HL048801)
- National Cancer Institute (CA-45448, CA47397)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK49216)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- epidermal growth factor receptor, zebrafish, cardiovascular development, EGFR kinase inhibitors, morpholino antisense, heart development, outflow tract, blood circulation, MAPK signaling, receptor tyrosine phosphorylation
- MeSH terms
- Amino Acid Sequence, Animals, Humans, Molecular Sequence Data, Pyrimidines, Pyrroles, Quinazolines, Zebrafish, Cardiovascular Abnormalities, Tyrphostins, Rats, ErbB Receptors
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