Changes in cell-cell adhesion play a critical role in embryonic development. There are numerous examples in development in which cells undergo a transition from an epithelial (strongly adherent) state to a mesenchymal (weakly adherent) state, and vice versa. Clearly, an understanding of how such epithelia/mesenchymal transitions are regulated is necessary for a proper understanding of tissue formation in embryogenesis. Epithelial/mesenchymal transitions generally result from inductive events in the embryo, so signal transduction via cell surface receptors is likely to play a role in the process. Pagliaccio (Pag) is an Eph-class receptor tyrosine kinase (RTK) that is expressed in Xenopus embryos in a highly localized set of tissues, including a subset of cranial neural crest cells, which are mesenchymal in nature. When Pag catalytic activity is activated ectopically in early embryos, cells disaggregate. The hypothesis to be tested in the proposed project is that the normal function of Pag in Xenopus embryos is to negatively regulate cell adhesion, thereby playing a role in effecting epithelial to mesenchymal transitions. The hypothesis will be tested by examining the cellular effects of Pag catalytic activity. Experiments will be performed to determine whether epithelial cells (both in culture and in embryos) in which Pag has been activated adopt a mesenchymal phenotype, express mesenchymal-specific markers, and exhibit a rearrangement of the actin cytoskeleton.
