Maintenance and Remodeling of Epithelial Cell-Cell Junctions in Response to Cell Shape Changes

Ann Miller's lab at the University of Michigan aims to identify mechanisms that promote maintenance, reinforcement, and remodeling of cell-cell adhesion and barrier function in response to cell-scale and tissue-scale forces. Epithelial cell-cell junctions including adherens junctions, tight junctions, and tricellular junctions adhere epithelial cells to one another, transmit forces between cells, and generate barrier function that selectively regulates what can pass in the paracellular space between cells. Each of these cell-cell junctions is connected to a contractile apical actomyosin array, and the connections between junctional proteins and the cytoskeleton are highly dynamic. Cells sense their mechanical environment as mechanical forces challenge cell-cell junctions – from cell-scale forces like a dividing cell pulling on its neighbors, to tissue-scale forces like morphogenesis sculpting the organism. Epithelial cells modulate their cell-cell junctions and connections to the actin cytoskeleton to ensure a stable yet adaptable architecture. My group seeks to understand how signaling proteins like Rho GTPases, RhoGEFs & RhoGAPs, scaffolding proteins, mechanosensitive proteins, calcium, and the cytoskeleton work together to create a strong but flexible epithelial barrier. Our research utilizes developing Xenopus laevis embryos as a model for the vertebrate epithelium, an array of innovative molecular tools for live microscopy of key molecular players, a live imaging barrier assay we developed, and several approaches to mechanically challenge the epithelium either globally or locally.