Distinct functions of Wnt/beta-catenin signaling in KV development and cardiac asymmetry.
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.
Lin
Xueying
X
Department of Biochemistry and Molecular Biology, Division of Cardiovascular Diseases, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. lin.xueying@mayo.edu
Xu
Xiaolei
X
D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D050980:GATA Transcription Factors / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D017491:Genes, APC; D006321:Heart / Q000196:embryology*; D055458:Left-Right Determination Factors / Q000235:genetics / Q000502:physiology; D008955:Models, Cardiovascular; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics / Q000502:physiology*; D060508:Wnt3 Protein; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000502:physiology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology*; D051176:beta Catenin / Q000235:genetics / Q000502:physiology*
D017931:DNA Primers; D050980:GATA Transcription Factors; C525957:Gata4 protein, zebrafish; D055458:Left-Right Determination Factors; D051153:Wnt Proteins; D060508:Wnt3 Protein; D029961:Zebrafish Proteins; D051176:beta Catenin; C495269:ctnnb1 protein, zebrafish; C117508:lft1 protein, zebrafish