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Embryonic development is disrupted by modest increases in vascular endothelial growth factor gene expression
L Miquerol1, B L Langille, A Nagy
1Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada.
Development (Cambridge, England)
|August 23, 2000
Summary
Vascular endothelial growth factor-A (VEGF-A) overexpression causes severe heart defects and embryonic lethality in mice. Precise VEGF-A levels are crucial for normal embryonic development and survival.
Area of Science:
- Developmental biology
- Cardiovascular research
- Molecular genetics
Background:
- Reduced vascular endothelial growth factor-A (VEGF-A) expression (50%) leads to embryonic lethality by embryonic day 9.5.
- VEGF-A is critical for embryonic development, particularly vascular and cardiac systems.
Purpose of the Study:
- To investigate the effects of VEGF-A overexpression on embryonic development.
- To determine the impact of elevated VEGF-A levels on heart formation and embryonic survival.
Main Methods:
- Generation of mouse models with two- to threefold overexpression of VEGF-A from its endogenous locus.
- Detailed analysis of embryonic heart development, including morphology and vascularization.
Main Results:
- Overexpression of VEGF-A resulted in embryonic lethality between embryonic days 12.5 and 14.
- Mutant embryos exhibited attenuated compact myocardium, excessive trabeculae, defective ventricular septation, and outflow tract remodeling issues.
- Aberrant coronary development included oversized epicardial vessels formed via vasculogenesis.
Conclusions:
- Embryonic survival is dependent on maintaining VEGF-A expression within a narrow physiological range.
- Both insufficient and excessive VEGF-A levels disrupt critical developmental processes, leading to embryonic lethality.