Cardiovascular Research Advance Access first published online on July 21, 2009
This version [Corrected Proof] published online on August 8, 2009
Cardiovascular Research, doi:10.1093/cvr/cvp254
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Wnt-11 signalling controls ventricular myocardium development by patterning N-cadherin and β-catenin expression
1 Laboratory of Developmental Biology, Department of Medical Biochemistry and Molecular Biology, Oulu Center for Cell-Matrix Research, Biocenter Oulu and Institute of Biomedicine, University of Oulu, PO Box 5000, 90014 Oulu, Finland
2 Department of Physiology, Biocenter Oulu and Institute of Biomedicine, University of Oulu, PO Box 5000, 90014 Oulu, Finland
3 Biocenter Oulu, University of Oulu, PO Box 5000, 90014 Oulu, Finland
4 Department of Obstetrics and Gynecology, Oulu University Hospital, Oulu, Finland
* Corresponding author. Tel: +358 8 537 6084, Fax: +358 8 537 6115, Email: seppo.vainio{at}oulu.fi
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.
KEYWORDS Wnt-11; Cardiogenesis; Myocardium; Echocardiography; Cadherin; Cytoskeleton
Time for primary review: 26 days
Present address. Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, Finland.
Present address. Department of Obstetrics and Gynecology, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.