Podoplanin and the posterior heart field : epicardial-myocardial interaction

This thesis introduces the posterior heart field contributing to the venous pole of the heart by epithelial-mesenchymal-transformation of the coelomic epithelium. Based on studying of podoplanin and Sp3 (novel genes in cardiogenesis) wildtype and knockout mouse embryos between stages 9.5-18.5, we postulate that the posterior heart field contributes through mesenchymal and myocardial cell populations. The mesenchymal population is involved in the formation of the proepicardial organ, epicardium and epicardium-derived cells. The hypoplastic proepicardial organ and impaired epicardial-myocardial interaction result from altered mesenchymal contribution of the posterior heart field by lack of podoplanin and SP3 leading to hypoplasia of the chamber myocardium and coronary arterial vascular wall as well as (atrioventricular) septal defects. Myocardial contribution concerns myocardium of the sinus venosus including the sinoatrial node, venous valves, primary atrial septum and the left atrial dorsal wall as well as the wall of the pulmonary and cardinal veins. Development of smooth-muscle-cells of the wall of the pulmonary vein is also related to the posterior heart field. Moreover, we have reported formation of a transient left-sided sinoatrial node which persists during development in 10% of the cases. Podoplanin mutants show cardiac malformations including a hypoplastic sinoatrial node. This thesis contributes to the understanding of the mechanism underlying the mentioned cardiac malformations and arrhythmias originating in the sinus venosus region.Nederlandse Hartstichting J.E. Jurriaanse Stichting Sanofi-aventis Netherlands B.V. Datascope Bristol-Myers SquibbUBL - phd migration 201