In organisms such as humans, internal organs within the body are evenly distributed throughout the body cavities. However, the "rudiments" of the respective organs arise from nearby locations within the fetus. The orderly arrangement of the organs depends on "directed cell migration," a process whereby the precursors of a specific organ, such as the heart, move from its site of origin to its final location in the adult body. Disruptions in directed cell migration cause many human diseases, including congenital heart defects (cardia bifida). It has been very difficult to study directed cell migration in vertebrate embryos, even relatively simple vertebrates such as fish and frogs, since the progenitors of the heart and other internal organs consist of hundreds or thousands of cells at the time of their migration. During the past few years the Levine lab has developed a simple model organism for studying heart migration, the sea squirt or ascidian, Ciona intestinalis. A variety of recent molecular studies suggest that the sea squirts are the closest living relative of the vertebrates and the same basic mechanisms of cell migration are likely used for heart cell migration in sea squirts and vertebrates. However, it is much easier to study this process in the sea squirt tadpole since it is composed of relatively few cells. At the time of its migration the sea squirt heart rudiment is composed of just four cells. In the proposed work, the Levine lab will identify and characterize the genes required for heart cell migration. The basic mechanisms revealed in this study should apply to heart cell migration in vertebrates, including humans. The Broader Impacts of this work include the elaboration of the fundamental principles of heart development using a powerful, yet simple, model system, generation of resources for the Ciona community, and training of a wide range of researchers, from undergraduates to postdoctoral fellows.
