http://repub.eur.nl/res/aut/20319/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/16889/ 2009-09-30T00:00:00Z In early embryonic life, the primitive heart tube consists of two layers, the myocardium and the endocardium. Eventually the heart tube loops to form a four-chambered structure providing for a circulation of blood by rhythmic contractions of the myocardium. With the increase in heart size and myocardial work load, a separate vasculature for the free myocardial wall is required. The formation of this coronary system is preceeded by the outgrowth of the epicardium, covering the naked heart tube. Our studies were performed on quail and chicken embryos, because of the high resemblance with human cardiac development. Avian embryos develop in approximately three weeks and were staged according to the Hamburger&Hamilton (HH) stages. In avian embryos the epicardial development starts at stage HH15 which is at three days of embryonic development, and is completed at stage HH25, which is after seven days of incubation. Epicardial cells are derived from the proepicardial organ (PEO), that protrudes as a cauliflower-like structure from the mesothelial lining of the body cavity near the sinus venosus and primitive liver, towards the inner curvature of the heart. The villi of the PEO reach the heart at the posterior atrial side where the sinus venosus myocardium is incorporated and the epicardial cells start to spread over the naked heart tube, until they eventually cover the myocardium completely. http://repub.eur.nl/res/pub/29741/ 2008-09-01T00:00:00Z The epicardium is embryologically formed by outgrowth of proepicardial cells over the naked heart tube. Epicardium-derived cells (EPDCs) migrate into the myocardium, contributing to myocardial architecture, valve development, and the coronary vasculature. Defective EPDC formation causes valve malformations, myocardial thinning, and coronary defects. In the atrioventricular (AV) valves and the fibrous heart skeleton isolating atrial from ventricular myocardium, EPDCs colocalize with periostin, a matrix molecule involved in remodeling. We investigated whether proepicardial outgrowth inhibition affected periostin expression and how this related to development of the AV valves and fibrous heart skeleton. Periostin expression by epicardium and EPDCs was confirmed in vitro in primary cultures of human and quail EPDCs. Disturbing EPDC formation in quail embryos reduced periostin expression in the endocardial cushions and AV junction. Disturbed fibrous tissue development resulted in AV myocardial connections reflected by preexcitation electrocardiographic patterns. We conclude that EPDCs are local producers of periostin. Disturbance of EPDC formation results in decreased cardiac periostin levels and hampers the development of fibrous tissue in AV junction and the developing AV valves. The resulting cardiac anomalies might link to Wolff-Parkinson White syndrome with persistent AV myocardial connections.