IMMUNOREACTIVITY OF THE ETS-1 TRANSCRIPTION FACTOR CORRELATES WITH AREAS OF EPITHELIAL-MESENCHYMAL TRANSITION IN THE DEVELOPING AVIAN HEART

Cardiac morphogenesis involves substantial remodeling processes that i nclude cell transdifferentiation and migration. The c-ets-1 protooncog ene codes for a transcription factor that can transactivate a number o f genes involved in developmental processes such as degradation of ext racellular matrices and cell migration. We have immunolocated the ets- 1 protein in the heart of quail and chick embryos between the Hamburge r and Hamilton stages HH16 and HH37. In HH16-17 embryos, the ets-l tra nscription factor was only detected in some endocardial cells and in m ost mesothelial and mesenchymal cells of the proepicardium. Ets-1 immu noreactivity increased markedly in the developing endocardial cushions , myocardium, epicardium and early subepicardial mesenchyme of HH18-19 embryos. By HH20-24 the immunoreactivity was found throughout the hea rt, with a stronger intensity in the areas of epithelial-mesenchymal t ransition of the endocardium and epicardium. In embryos between HH26 a nd HH33, ets-1 immunoreactivity increased in the cushion mesenchyme, a trioventricular endocardium, ventricular epicardium and subepicardial mesenchyme cells, but not in other areas of the heart. The immunoreact ivity declined in the innermost part of the endocardial cushions. The subepicardial mesenchyme was particularly immunoreactive in these stag es, coinciding with the development of the subepicardial vascular netw ork. In fact, ets-1 colocalized with the quail vascular marker QH1 in the subepicardial mesenchymal cells. Ets-1-negative cells were abundan t in the subepicardium and valvuloseptal tissue of the HH37 embryos. T he results suggest that ets-1, probably through transactivation of gen es such as urokinase-type plasminogen activator and matrix metalloprot einases, might play a crucial role in the differentiation of the cushi on and subepicardial mesenchyme, the formation of the intratrabecular sinusoids and the early development of the cardiac vessels.