Constitutive over-expression of VEGF results in reduced expression of Hand-1 during cardiac development in Xenopus.
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.
Nagao
Kaori
K
Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan.
Taniyama
Yoshiaki
Y
Koibuchi
Nobutaka
N
Morishita
Ryuichi
R
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D015415:Biomarkers; D004625:Embryo, Nonmammalian / Q000098:blood supply / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D009206:Myocardium / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D042461:Vascular Endothelial Growth Factor A; C097341:helix-loop-helix protein, eHAND