During embryonic heart development, a population of endothelial cells within a region of the atrioventricular canal undergoes a phenotypic transformation to form migratory mesenchymal cells. These cells are the earliest progenitors of the valves and membranous septa of the heart. During the previous funding period we described mechanisms of cell transformation and migration which are mediated through interactions with the extracellular matrix. Proposed studies would extend these results by examining the regulation of cell surface galactosyltransferase, a receptor used during cell migration, after cell transformation in the chick embryo. These studies will determine whether an increase in enzyme activity is due to increased transcription, translation or post-translational events. We will also examine the effects of a loss of GalTase expression in chicken and mouse cardiac mesenchymal cells by the use of modified antisense oligonucleotides. Preliminary data suggests this enzyme is aberrantly upregulated in human cardiac fibroblasts from Down's patients with congenital heart disease. This may be the cause of a reported difference in cell adhesivity which has been postulated to account for the AV canal defect which is common in Down's patients. We will compare regulation of galactosyltransferase between cardiac and dermal fibroblasts of both Down's and non-Down's origin. Comparison will also be made for several additional mechanisms of cell-cell and cell-extracellular matrix adhesion. These studies will continue our investigations of normal embryonic cardiac development in the embryo and directly examine a hypothesis for the etiology of congenital heart disease in humans. Such studies may provide a useful link between an experimental model and malformations of the heart which occur in humans.
| Huang, J X; Potts, J D; Vincent, E B et al. (1995) Mechanisms of cell transformation in the embryonic heart. Ann N Y Acad Sci 752:317-30 |
| Runyan, R B; Potts, J D; Weeks, D L (1992) TGF-beta 3-mediated tissue interaction during embryonic heart development. Mol Reprod Dev 32:152-9 |
| Runyan, R B; Potts, J D; Sharma, R V et al. (1990) Signal transduction of a tissue interaction during embryonic heart development. Cell Regul 1:301-13 |
| Loeber, C P; Runyan, R B (1990) A comparison of fibronectin, laminin, and galactosyltransferase adhesion mechanisms during embryonic cardiac mesenchymal cell migration in vitro. Dev Biol 140:401-12 |
| Potts, J D; Runyan, R B (1989) Epithelial-mesenchymal cell transformation in the embryonic heart can be mediated, in part, by transforming growth factor beta. Dev Biol 134:392-401 |
