Frzb modulates Wnt-9a-mediated β-catenin signaling during avian atrioventricular cardiac cushion development

被引:62
|
作者
Person, AD
Garriock, RJ
Krieg, PA
Runyan, RB
Klewer, SE
机构
[1] Univ Arizona, Med Ctr, Dept Cell Biol & Anat, Sch Med, Tucson, AZ 85724 USA
[2] Univ Arizona, Sch Med, Dept Pediat, Tucson, AZ 85724 USA
基金
美国国家卫生研究院;
关键词
Wnt-9a; Wnt-14; Frzb; endocardial cushions; cell proliferation; apoptosis; beta-catenin; epithelial-mesenchymal transition (EMT); heart; cardiac;
D O I
10.1016/j.ydbio.2004.10.013
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Normal development of the cardiac atrioventricular (AV) endocardial cushions is essential for proper ventricular septation and morphogenesis of the mature mitral and tricuspid valves. In this study, we demonstrate spatially restricted expression of both Wnt-9a (formerly Wnt-14) and the secreted Wnt antagonist Frzb in AV endocardial cushions of the developing chicken heart. Wnt-9a expression is detected only in AV canal endocardial cells, while Frzb expression is detected in both endocardial and transformed mesenchymal cells of the developing AV cardiac cushions. We present evidence that Wnt-9a promotes cell proliferation in the AV canal and overexpression of Wnt-9a in ovo results in enlarged endocardial cushions and AV inlet obstruction. Wnt-9a stimulates beta-catenin-responsive transcription in AV canal cells, duplicates the embryonic axis upon ventral injections in Xenopus embryos and appears to regulate cell proliferation by activating a Wnt/beta-catenin signaling pathway. Additional functional studies reveal that Frzb inhibits Wnt-9a-mediated cell proliferation in cardiac cushions. Together, these data argue that Wnt-9a and Frzb regulate mesenchymal cell proliferation leading to proper AV canal cushion outgrowth and remodeling in the developing avian heart. (C) 2004 Published by Elsevier Inc.
引用
收藏
页码:35 / 48
页数:14
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