Regional differences in WT-1 and Tcf21 expression during ventricular development: implications for myocardial compaction

BACKGROUND: 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 Wt1(CreERT2/+) reporter mice were used to study WT-1 expressing cells, and Tcf21(lacZ/+) reporter mice and PDGFRα(-/-);Tcf21(LacZ/+) 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(-/-);Tcf21(LacZ/+) 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.