Abstract-In the development of a functional myocardium and formation of the coronary vasculature, epicardium-derived cells play an essential role. The proepicardial organ contributes to the developing coronary system by delivering mural cells to the endothelium-lined vessels. In search of genes that regulate the behavior of (pro)epicardial cells, the Ets-1 and Ets-2 transcription factors stand out as strong candidates. In the present study, the hypothesis that Ets transcription factors have a role in proper coronary and myocardial development was tested via antisense technology, by targeting Ets-1 and Ets-2 mRNAs to downregulate protein expression in chicken embryos. The results suggest that hereby the development of the coronary system is hampered, primarily by defects in the process of epithelial-mesenchymal transformation of the mesothelia of the primary and secondary heart fields. This was indicated by a lack of periarterial and epicardial mesenchyme, of peripheral coronary smooth muscle cells, and changes in myocardial morphology. A defect in myocardial perfusion caused by the absence of one or both coronary ostia seems to be "solved" by the development of numerous small fistulae connecting the ventricular lumen with the subepicardially located coronary vessels. The presence of coronary vascular aberrations in the antisense-Ets phenotype enabled us for the first time to study abnormal coronary development in a model that is not lethal to the embryo. Key Words: Ets transcription factors Ⅲ epicardium Ⅲ coronary arteries Ⅲ myocardium Ⅲ development I nitially, the developing heart consists of a myocardial tube lined with endocardium, with cardiac jelly in between. With the increase in myocardial functioning, a separate vasculature of the myocardial wall becomes necessary. The formation of the coronary system is preceded by the outgrowth of the proepicardial organ over the heart to form the epicardium, 1 followed by infiltration of endothelial cells from the septum transversum into the subepicardial space to form a capillary network. 2 Subsequently, epicardial cells transdifferentiate and migrate to form the subepicardial and subendocardial mesenchyme. These mesenchymal cells then differentiate into smooth muscle cells (SMCs) and adventitial fibroblasts of the coronary vessel walls, 3 into myocardial interstitial fibroblasts, subendocardial cells, and cells in the cushion mesenchyme. 4 Quail-chicken chimeras showed that the endocardium of the ventricular lumen does not contribute to the formation of the coronary vasculature. 5 The long held idea that coronary arteries develop by endocardial budding from the trabecular folds could thus be refuted. 3 This implies that the presence of fistulae in some congenital heart malformations like pulmonary atresia without ventricular septal defects 6 are not the result of such persisting luminized embryonic connections. Recent studies indicate that fistulae can in fact be the initial problem in the developing myocardium, and that secondarily, the pulmonary stenosis to atresi...

The beneficial effect of additional folic acid in the periconceptional period to prevent neural tube defects, orofacial clefts, and conotruncal heart defects in the offspring has been shown.

This study demonstrates that homocysteine disturbs apoptosis and myocardialization of the outflow tract, probably by affecting the cardiac neural crest cells.

Quantitative mapping of the normal tissue dynamics of an entire developing mammalian organ has not been achieved so far but is essential to understand developmental processes and to provide quantitative data for computational modeling. We developed a four-dimensional (4D) imaging technique that can be used to quantitatively image tissue movements and dynamic GFP expression domains in a growing transgenic mouse limb by time-lapse optical projection tomography (OPT).