Distinct phases of Wnt/β-catenin signaling direct cardiomyocyte formation in zebrafish

Dohn, T.E., and Waxman, J.S.
Developmental Biology   361(2): 364-76 (Journal)
Registered Authors
Waxman, Joshua
cardiomyocyte, differentiation, wnt signaling, zebrafish
MeSH Terms
  • Animals
  • Body Patterning/genetics
  • Caspase 3/metabolism
  • Cell Death
  • Cell Differentiation/genetics
  • Enzyme Activation
  • Gastrula/cytology
  • Gastrula/metabolism
  • Gastrulation/genetics
  • Gene Expression Regulation, Developmental
  • Heart Atria/cytology
  • Heart Atria/embryology
  • Heart Atria/metabolism
  • Heart Ventricles/cytology
  • Heart Ventricles/embryology
  • Heart Ventricles/metabolism
  • Mesoderm/cytology
  • Mesoderm/embryology
  • Mesoderm/metabolism
  • Models, Biological
  • Myocytes, Cardiac/cytology*
  • Myocytes, Cardiac/enzymology
  • Myocytes, Cardiac/metabolism*
  • Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Somites/embryology
  • Wnt Signaling Pathway*/genetics
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
22094017 Full text @ Dev. Biol.
Normal heart formation requires reiterative phases of canonical Wnt/β-catenin (Wnt) signaling. Understanding the mechanisms by which Wnt signaling directs cardiomyocyte (CM) formation in vivo is critical to being able to precisely direct differentiated CMs from stem cells in vitro. Here, we investigate the roles of Wnt signaling in zebrafish CM formation using heat-shock inducible transgenes that increase and decrease Wnt signaling. We find that there are three phases during which CM formation is sensitive to modulation of Wnt signaling through the first 24 h of development. In addition to the previously recognized roles for Wnt signaling during mesoderm specification and in the pre-cardiac mesoderm, we find a previously unrecognized role during CM differentiation where Wnt signaling is necessary and sufficient to promote the differentiation of additional atrial cells. We also extend the previous studies of the roles of Wnt signaling during mesoderm specification and in pre-cardiac mesoderm. Importantly, in pre-cardiac mesoderm we define a new mechanism where Wnt signaling is sufficient to prevent CM differentiation, in contrast to a proposed role in inhibiting cardiac progenitor (CP) specification. The inability of the CPs to differentiate appears to lead to cell death through a p53/Caspase-3 independent mechanism. Together with a report for an even later role for Wnt signaling in restricting proliferation of differentiated ventricular CMs, our results indicate that during the first 3 days of development in zebrafish there are four distinct phases during which CMs are sensitive to Wnt signaling.
Genes / Markers
Show all Figures
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes