Abstract
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.
Original language | English (US) |
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Pages (from-to) | 207-217 |
Number of pages | 11 |
Journal | Development |
Volume | 136 |
Issue number | 2 |
DOIs | |
State | Published - Jan 15 2009 |
Keywords
- Gata4
- Left-right asymmetry
- Lefty2
- Wnt signaling
- Zebrafish
ASJC Scopus subject areas
- Molecular Biology
- Developmental Biology