PROJECT SUMMARY Many epithelial tissues are two-dimensional sheets of cells. Recent work from multiple systems shows that a misplaced epithelial cell can reintegrate back into the sheet, and suggest that this process is a common feature of tissue development. We aim to understand this process. Our previous work in the fruit fly Drosophila melanogaster showed that cell reintegration fails in the absence of homophilic adhesion molecules that line cell-cell borders. This observation raises the question of whether the same molecules mediate reintegration in other systems. Our preliminary work also suggests that these molecules coordinate with other structural components to remodel the cell after division, and that it is this process that drives reintegration. We propose three specific aims: 1) Determine whether lateral adhesion mediates reintegration in three- dimensional cultured vertebrate tissue systems. 2A) Find out whether reintegration requires cooperation between adhesion molecules and cytoskeletal components. 2B) Establish whether reintegrative capacity is limited to newly-born cells. This work will illuminate cell reintegration, a fundamental property of epithelial tissues, and help to explain its importance to tissue development and maintenance.