Frzb modulates Wnt-9a-mediated beta-catenin signaling during avian atrioventricular cardiac cushion development.
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.
Person
Anthony D
AD
Department of Cell Biology and Anatomy, University Medical Center, University of Arizona School of Medicine, 1501 N. Campbell Avenue, PO Box 245044, Tucson, AZ 85724, USA. aperson@email.arizona.edu
Garriock
Robert J
RJ
Krieg
Paul A
PA
Runyan
Raymond B
RB
Klewer
Scott E
SE
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001283:Atrioventricular Node / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D001483:Base Sequence; D049109:Cell Proliferation; D002642:Chick Embryo; D003598:Cytoskeletal Proteins / Q000502:physiology*; D004247:DNA / Q000235:genetics; D051157:Frizzled Receptors; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D015534:Trans-Activators / Q000502:physiology*; D051153:Wnt Proteins; D051176:beta Catenin
D003598:Cytoskeletal Proteins; D051157:Frizzled Receptors; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D051176:beta Catenin; D004247:DNA