Regional differences in WT-1 and Tcf21 expression during ventricular development: implications for myocardial compaction
Scherptong, Roderick W. C.
Kruithof, Boudewijn P. T.
Duim, Sjoerd N.
Goumans, Marie Jose T. H.
Wisse, Lambertus J.
Poelmann, Robert E.
Schalij, Martin J.
Tallquist, Michelle D.
Gittenberger-de Groot, Adriana C.
Jongbloed, Monique RMNote: Order does not necessarily reflect citation order of authors.
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CitationVicente-Steijn, R., R. W. C. Scherptong, B. P. T. Kruithof, S. N. Duim, M. J. T. H. Goumans, L. J. Wisse, B. Zhou, et al. 2015. “Regional differences in WT-1 and Tcf21 expression during ventricular development: implications for myocardial compaction.” PLoS ONE 10 (9): e0136025. doi:10.1371/journal.pone.0136025. http://dx.doi.org/10.1371/journal.pone.0136025.
AbstractBackground: Morphological and functional differences of the right and left ventricle are apparent in the adult human heart. A differential contribution of cardiac fibroblasts and smooth muscle cells (populations of epicardium-derived cells) to each ventricle may account for part of the morphological-functional disparity. Here we studied the relation between epicardial derivatives and the development of compact ventricular myocardium. Results: Wildtype and Wt1CreERT2/+ reporter mice were used to study WT-1 expressing cells, and Tcf21lacZ/+ reporter mice and PDGFRα-/-;Tcf21LacZ/+ mice to study the formation of the cardiac fibroblast population. After covering the heart, intramyocardial WT-1+ cells were first observed at the inner curvature, the right ventricular postero-lateral wall and left ventricular apical wall. Later, WT-1+ cells were present in the walls of both ventricles, but significantly more pronounced in the left ventricle. Tcf21-LacZ + cells followed the same distribution pattern as WT-1+ cells but at later stages, indicating a timing difference between these cell populations. Within the right ventricle, WT-1+ and Tcf21-lacZ+ cell distribution was more pronounced in the posterior inlet part. A gradual increase in myocardial wall thickness was observed early in the left ventricle and at later stages in the right ventricle. PDGFRα-/-;Tcf21LacZ/+ mice showed deficient epicardium, diminished number of Tcf21-LacZ + cells and reduced ventricular compaction. Conclusions: During normal heart development, spatio-temporal differences in contribution of WT-1 and Tcf21-LacZ + cells to right versus left ventricular myocardium occur parallel to myocardial thickening. These findings may relate to lateralized differences in ventricular (patho)morphology in humans.
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