The physiological process that maintains a constant number of cells in a renewing organ is called tissue homeostasis. Tissue homeostasis requires the cells to act as a network with coordinated cell movement, as well as spatiotemporally regulated proliferation and differentiation events. The mammalian skin is ideal for investigating the mechanisms of this process, as it undergoes self-renewal throughout the lifetime of the organism. Our research addresses two fundamental questions: What are the basic principles that govern the balance of proliferation and differentiation enable the maintenance of the skin as a robust but continuously self-renewing organ? How do the dynamics of this balance change upon aging resulting in tissue dysfunction and disease?

 The mechanisms of cell movement, proliferation and differentiation have been mainly uncovered in cell culture systems. However, for network formation in a tissue, cell-cell and cell-matrix interactions are of enormous importance. The adjustment of cellular networks to functional requirements of life can thus be solely studied in an intact organism or in vitro systems that recapitulate this complexity. We postulate that mechanical signals, stresses and shape changes provide important local controls that regulate skin homeostasis. However, very little is known about the molecular mechanisms of this type of regulation, particularly in vivo. This project aims to understand how contractile properties of the cytoskeleton in co-operation with cell-matrix interactions, by providing spatial information and by generating and sensing biomechanical signals, impact on epidermal homeostasis. We apply a combination of mouse genetics and cell biology to address these questions. These systems are analyzed using state-of-the-art live cell imaging, supported by cell biological and biochemical approaches.