EPITHELIAL-MESENCHYMAL TRANSFORMATIONS IN EARLY AVIAN HEART DEVELOPMENT

Cardiac morphogenesis proceeds from a sequential series of epithelial- mesenchymal transitions which begins by establishing bipotential heart -forming cells and later their segregation into endocardial and myocar dial lineages. Cells within each lineage integrate to form two concent ric epithelia which inductively interact to transform cells of the inn er epithelium, the endocardium, into mesenchymal or 'cushion' cells. N oncardiogenic epithelia (dorsal mesocardium, epicardium, neural ectode rm and coelomic mesothelium) undergo transition into populations of ex tracardiac mesenchyme that combine over time with cushion tissue to re model the simple tubular heart into a four-chambered organ. Model syst ems are described for studying the mechanisms of cardiac-related trans formations including primary cultures of precardiac epithelia and a di fferentiation-inducible, avian stem cell line called QCE-6, Focus is c entered on the molecular mechanism by which endocardial epithelium tra nsforms into cushion mesenchyme. Experimental findings are reviewed an d interpreted in the context of a hypothetical model that seeks to ans wer why only some cells within an epithelium transform and whether the transformation process is regulated by intrinsic or extrinsic mechani sms. The model proposes that epithelial cells competent to transform t o mesenchyme express characteristic markers including receptors for ex trinsic signals secreted by stimulator cells (e.g. myocardium). Candid ate extrinsic signals include multicomponent complexes called adherons . If applied directly to cultured endocardium, myocardial adherons but not those secreted by L6 myoblasts, induce changes in gene expression within target endocardial cells for proteases and cell:cell and cell: matrix adhesion molecules that accompanied transformation to mesenchym e. A main component of myocardial adherons has been identified as ES a ntigens, one of which, ES/130, has been cloned, found to have a novel sequence and in culture assays shown to be required for endocardium to transform to mesenchyme. The spatiotemporal pattern of ES protein exp ression within the embryo suggests that common mechanisms may exist fo r embryonic epithelial-mesenchymal transformations.