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First published online December 22, 2008
doi: 10.1242/10.1242/dev.029561

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Distinct functions of Wnt/β-catenin signaling in KV development and cardiac asymmetry

Department of Biochemistry and Molecular Biology, Division of Cardiovascular Diseases, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.

e-mails: lin.xueying{at}mayo.edu; xu.xiaolei{at}mayo.edu

Accepted 30 October 2008

The Wnt/β-catenin pathway exhibits distinct and developmental stage-specific roles during cardiogenesis. However, little is known about the molecular mechanisms of Wnt/β-catenin signaling in the establishment of cardiac left-right (LR) asymmetry. Using zebrafish as an animal model, we show here that Wnt/β-catenin signaling is differentially required in cardiac LR patterning. At an early stage, during asymmetric signal generation, Wnt/β-catenin signaling is necessary for Kupffer's vesicle development and for the regulation of both heart and visceral laterality. At a later stage, during asymmetric signal propagation, excessive Wnt/β-catenin signaling inhibits the transmission of asymmetric cues from the lateral plate mesoderm (LPM) to the cardiac field but not to the developing gut; as such, it only regulates heart laterality. Molecular analysis identifies Gata4 as the downstream target of Wnt/β-catenin signaling in the cardiac field that responds to the Wnt/β-catenin signaling and regulates the competence of the heart field to express left-sided genes. In summary, our results reveal a previously unexpected role of Wnt-Gata4 signaling in the control of asymmetric signal propagation from the LPM to the cardiac field.

Key words: Left-right asymmetry, Wnt signaling, Gata4, Lefty2, Zebrafish

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