PROJECT SUMMARY Simple epithelial tissues are monolayered sheets of cells. As they divide, epithelial cells commonly move apically (upward), sometimes to the point that they are protruding out of the sheet. The daughter cells must then reintegrate back down into it. This process appears to be a normal feature of tissue development. We aim to understand how it works. Our work in the fruit fly Drosophila melanogaster shows that cell reintegration relies on partially-redundant adhesion molecules that line cell-cell borders, but it is not yet clear if these molecules are part of a dedicated machinery or if they simply contribute (in sum) to an amount of adhesion that is required for cells to reintegrate. In the first aim we propose to test between these possibilities using traditional Drosophila genetics and imaging. Another open question about epithelial cell reintegration is whether it requires active participation from neighboring cells (“welcoming” in the new cell) or if instead the reintegrating cell just pushes its neighbors out of the way. In the second aim we propose to use cultured Madin-Darby Canine Kidney (MDCK) cells to investigate the behavior of the neighboring cells. Together, the proposed work will illuminate cell reintegration, a fundamental property of epithelial tissues, and help to explain its importance to tissue development and maintenance.