Journal
DEVELOPMENT
Volume 136, Issue 2, Pages 207-217Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dev.029561
Keywords
Left-right asymmetry; Wnt signaling; Gata4; Lefty2; Zebrafish
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Funding
- AHA SDG [0735232N]
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The Wnt/beta-catenin pathway exhibits distinct and developmental stage-specific roles during cardiogenesis. However, little is known about the molecular mechanisms of Wnt/beta-catenin signaling in the establishment of cardiac left-right (LR) asymmetry. Using zebrafish as an animal model, we show here that Wnt/beta-catenin signaling is differentially required in cardiac LR patterning. At an early stage, during asymmetric signal generation, Wnt/beta-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/beta-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/beta-catenin signaling in the cardiac field that responds to the Wnt/beta-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.
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