Summary

Tissue formation requires the coordination of forces across cells and tissue boundaries to drive cellular rearrangements. The skin epidermis is a self-renewing multi-layered stratifying epithelium and crucial for skin barrier function. Self-renewal of basal stem cells is balanced with a spatiotemporal controlled differentiation program of their progeny. This program is accompanied by spatial coordination of adherens junction and cytoskeletal organization and cell shape changes. However, it is not known whether junctional tension and cell shape changes control selfrenewal and differentiation programs. In the present proposal we ask how cadherins control coordinated by cadherins and whether this is important for epidermal morphogenesis and homeostasis. To this end we will characterize in depth how classical cadherins coordinate the structure and organization of adherens junctions and associated actomyosin cytoskeleton in the self-renewing epidermis using a combined imaging and proteomics approach on in vivo and in vitro models. We will further ask whether tension across cadherin complexes regulate epidermal adhesive and tensile strength and drive epidermal self-renewal, differentiation and intercellular migration. Together, the experiments proposed will likely contribute to a better understanding of the molecular mechanisms by which cadherin/catenin mechanosensing control the morphogenesis and homeostasis of stratifying epithelia.