The great arteries of the head and neck are derived from six pairs of aortic arches during early embryogenesis. Development and regression of the aortic arch pairs proceeds in an ordered and specific manner. During this process, ectomesenchymal cells migrate through the aortic arches, supplying cells that will contribute to some of the persisting arches and altering blood flow. Abnormal persistence or regression of these arches results in cardiovascular malformations such as interrupted aortic arch, patent ductus arteriosus and pulmonary atresia. This application for a Physician Scientist Award presents a comprehensive program to train the candidate in research methods needed to investigate the interactions of migrating ectomesenchymal cells and aortic arches in cardiovascular morphogenesis. The research plan for Phase I is presented. Phase II will be based on the developments of Phase I, but with an increased emphasis on the uses of cell and molecular biology. A faculty advisory committee will evaluate performance during Phase I, defense of the research proposal prior to initiating Phase II, and progress during Phase II. The purpose of this research proposal is to define the specific mechanisms of interaction between ectomesenchymal cells and the aortic arches that determine the selection of aortic arches in the chick embryo. Included in this plan are 1) the measurement of impedance in the aortic arches in normal chick embryos using modifications of current hemodynamic techniques, 2) measurement of aortic arch impedance in embryos after surgical ablation of cranial neural crest and the nodose placode, 3) tracking the migration of neural crest and nodose placode cells through the aortic arches and correlating their presence with changes in vascular impedance, and 4) the correlation of cell products, including pretropoelastin and glycosaminoglycans, and aortic arch impedance.
