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 beta-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.
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 beta-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.
Authors: Nadejda V Mezentseva; Jinpu Yang; Keerat Kaur; Grazia Iaffaldano; Mathieu C Rémond; Carol A Eisenberg; Leonard M Eisenberg Journal: Stem Cells Dev Date: 2012-11-07 Impact factor: 3.272
Authors: Patrick P van Vliet; Lizhu Lin; Cornelis J Boogerd; James F Martin; Gregor Andelfinger; Paul D Grossfeld; Sylvia M Evans Journal: Dev Biol Date: 2017-06-30 Impact factor: 3.582