Wnt-11 signalling controls ventricular myocardium development by patterning N-cadherin and β-catenin expression

Aims The stage-dependent organization of the cardiomyocytes during formation of the different layers of the developing ventricular wall is critical for the establishment of a functional heart, but the instructive signals involved are still poorly known. We have addressed the potential role of Wnt-11 in the control of early ventricular myocardium assembly. Methods and results We demonstrate by means of expression analysis and a mouse model in which Wnt-11 function has been inactivated that Wnt-11 is expressed by the embryonic ventricular cardiomyocytes and serves as one important signal for ventricular wall development. In the absence of Wnt-11, the coordinated organization, intercellular contacts, co-localized expression of the cell adhesion components N-cadherin and β-catenin, and the cytoskeleton of the differentiating ventricular cardiomyocytes are all disturbed. Moreover, the ventricular wall lacking Wnt-11 signalling is thinner and the expression of the Gata-4 , Nkx2.5 , Mef2c , ANP , and BNP genes is down-regulated relative to controls. These defects lie behind disturbed embryonic cardiac functional development, marked by an increase in the ventricular relaxation time during the early diastole. Conclusion We conclude that Wnt-11 signalling serves as a critical cell adhesion cue for the organization of the cardiomyocytes in the developing ventricular wall, which is essential for the establishment of a functional heart.