The role of polysialated NCAM in the normal development of the cardiac conduction system will be investigated in the chicken embryo model. The neural cell adhesion molecule NCAM and its polysialic acid moiety are modulators of cell-cell interactions found in the developing heart. Up and down regulation of these components during neural and skeletal muscle development is critical for creating the balance that results in normal morphogenetic patterns. In previous studies, the applicant has demonstrated that NCAM and PSA are regulated in their expression in developing heart tissue. She has also shown that perturbation of NCAM or PSA alters the function of gap junctions which couple myocardial cells and PSA-rich NCAM is found preferentially on ventricular conduction tissue. These findings has led the investigator to propose that NCAM and PSA are acting as they do on neuronal processes to allow plasticity in interactions of myocardial cells, particularly those of conduction tissue during cardiogenesis.
The aims of this study are: 1) to refine this hypothesis by determining the PSA distribution in regions and stages not yet studied in detail; and 2) to test their hypothesis by enzymatically removing PSA from the embryonic heart in ovo and assessing the consequences to the morphology, biochemistry and electrophysiology of the conduction system.
