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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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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org.

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

Irina I. Nagy1, Antti Railo1, Risto Rapila2, Terhi Hast1, Raija Sormunen3, Pasi Tavi2,{dagger}, Juha Räsänen4,{ddagger} and Seppo J. Vainio1,*

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

{dagger} Present address. Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, Finland.

{dagger} Present address. Department of Obstetrics and Gynecology, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.


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