ZFIN ID: ZDB-PUB-090106-17
Distinct functions of Wnt/{beta}-catenin signaling in KV development and cardiac asymmetry
Lin, X., and Xu, X.
Date: 2009
Source: Development (Cambridge, England)   136(2): 207-217 (Journal)
Registered Authors: Lin, Xueying, Xu, Xiaolei
Keywords: Left-right asymmetry, Wnt signaling, Gata4, Lefty2, Zebrafish
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Body Patterning/genetics
  • Body Patterning/physiology
  • DNA Primers/genetics
  • GATA Transcription Factors/genetics
  • GATA Transcription Factors/physiology
  • Gene Expression Regulation, Developmental
  • Genes, APC
  • Heart/embryology*
  • Left-Right Determination Factors/genetics
  • Left-Right Determination Factors/physiology
  • Models, Cardiovascular
  • Signal Transduction
  • Wnt Proteins/genetics
  • Wnt Proteins/physiology*
  • Wnt3 Protein
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/physiology*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
  • beta Catenin/genetics
  • beta Catenin/physiology*
PubMed: 19103803 Full text @ Development
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.