Abstract 1242: Wnt Signaling in the Mouse Heart: Effect of Wnt-11 on Cardiac Differentiation
Components of the Wnt signaling pathway have been implicated in cardiac function and regeneration but the exact mechanisms remain unknown. Expression analysis of various Wnt signaling components were analysed by RT-PCR. It was found that the Wnts were differentially expressed throughout cardiac development whereas the membrane bound Frizzled receptors for Wnts and the intracellular components of the pathway were present throughout cardiac development. The T-cell factor, TCF-LacZ (+/+) reporter mouse strain was used to analyse active canonical Wnt signaling in vivo. It was observed that canonical Wnt signaling has a more restricted region of activity in the mouse heart when compared to non-canonical Wnt signaling. Canonical Wnt signaling appears active primarily in the outflow tract of the heart whereas non-canonical Wnt signaling is present in the ventricular and atrial regions of the heart. Interestingly, the non-canonical Wnt-11 displayed a prominent bi-phasic expression pattern suggesting that this ligand may influence key events associated with cardiac development. Accordingly, the effects of Wnt-11 were further analysed in the cardiac-derived H9c2 cell line. Wnt-11 was over-expressed and secreted from H9c2 cells using a Wnt-11 adenovirus. It was observed that Wnt-11 promotes H9c2 differentiation into myosin heavy chain positive expressing cells during an 8 day low serum-induced differentiation time course when compared to a GFP control. During differentiation Wnt-11 also activated PKC, a marker of non-canonical Wnt/calcium signaling. Wnt-11 also inhibited stabilization of beta-catenin in a LiCl/beta-catenin stabilization assay suggesting that Wnt-11 inhibits canonical Wnt signaling. In conclusion, these results suggest that the heart is comprised of many Wnt signaling pathway components and that Wnt-11 may promote cardiac differentiation through suppression of the canonical Wnt pathway.