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Constitutive over-expression of VEGF results in reduced expression of Hand-1 during cardiac development in Xenopus
Kaori Nagao1, Yoshiaki Taniyama, Nobutaka Koibuchi
1Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan.
Insights
Overexpressing vascular endothelial growth factor (VEGF) in Xenopus embryos disrupted heart development, leading to abnormal morphology and impaired heart looping. Increased VEGF interfered with Hand-1 gene expression crucial for cardiac morphogenesis.
Area of Science:
- Developmental Biology
- Molecular Biology
- Cardiovascular Research
Background:
- Vascular endothelial growth factor (VEGF) signaling is critical for vascular and cardiac development.
- VEGF receptors are expressed in the embryonic heart, suggesting a role in heart formation.
Purpose of the Study:
- To investigate the effects of VEGF overexpression on heart development in Xenopus embryos.
- To understand the molecular mechanisms underlying VEGF-induced cardiac abnormalities.
Main Methods:
- Overexpression of VEGF(170) in Xenopus embryos.
- Analysis of vascular development using the endothelial marker Tie-2.
- Histological examination of heart morphology and looping.
- In situ hybridization to assess Hand-1 gene expression.
Main Results:
- VEGF overexpression led to disorganized vessels and increased Tie-2 expression.
- Embryonic hearts were enlarged and exhibited abnormal morphology, including failed heart looping.
- Hand-1 expression was significantly decreased in the heart region of VEGF-overexpressing embryos.
Conclusions:
- Increased VEGF(170) levels disrupt normal heart morphogenesis in Xenopus embryos.
- VEGF overexpression interferes with Hand-1 expression, a key regulator of cardiac development.
- VEGF levels are crucial for maintaining proper heart morphology during embryonic development.
Abstract:
During heart development, various signaling cascades are tightly regulated in a stage- and region-dependent manner. Vascular endothelial growth factor (VEGF) is one of the important molecules required for both vascular development and cardiac morphogenesis. VEGF receptors are present in the embryonic heart, so we focused on heart formation in VEGF-over-expressing Xenopus embryos. Over-expression of VEGF(170) caused disorganized vessels, while the expression of an endothelial marker, Tie-2, was increased. The embryo's heart was distinctly larger than that of control, and showed abnormal morphology. Histological analysis of these embryos showed failure of heart looping. In situ hybridization with Hand-1, which controls intrinsic morphogenetic pathways, revealed that the expression level of Hand-1 was decreased in the heart region. These results suggest that increased VEGF(170) levels disturb Hand-1 expression in the region required for normal heart morphogenesis. VEGF expression level may be important in heart morphology during embryonic development.
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