Cardiac function, Developmental biology, Heart, Kinase, Knockout, Molecular medicine, Pharmacology, Phosphorylation, Physiology, Receptor, Signal transduction, Vascular Biology, Pulmonary hypertension
The goal of our laboratory is to determine the common mechanisms by which growth factors mediate and influence organ formation during embryogenesis. We have a special interest in heart formation in the chick and currently focus on the Transforming Growth Factor-beta (TGF beta) family of peptide growth factors in atrioventricular (AV) cushion transformation and coronary vessel formation in the heart. Localized epithelial-mesenchymal transformation in specific regions of the heart, including the AV cushion and proepicardium, gives rise to the valves and membranous septa of the heart and coronary vessels, respectively. Using specific antibodies to immunolocalize TGF beta receptor types and to block specific receptor types in an in vitro model of AV cushion transformation, we have identified the TGF beta receptor complex that mediates of AV cushion transformation, we have identified the TGF beta receptor complex that mediates transformation. Further, misexpression of components of this complex by viral gene transfer converts normally unresponsive ventricular endocardial cells to transforming cells confirming the roles of specific receptors and downstream signing molecules. Experiments in the proepicardium indicate the TGF beta receptors play a similar role in coronary vessel formation. A number of strategies are being used to identify genes expressed by the AV cushion, developing valves and proepicardium. Finally, conditionally null mice are being generated to confirm and extend these results in mammals. These strategies are directed at determining the role that growth factors, like TGF beta, play in organ formation during embryogenesis.