BBB Seminar: Carien M. Niessen

Carien M. Niessen
Department of Dermatology, University of Cologne, Germany

The main research interest of my laboratory is to understand how the establishment, maintenance and restoration of cell and tissue architecture are coordinated with the growth, metabolism and innate immunity status of cells to drive morphogenesis and to maintain tissue homeostasis. Intercellular adhesion and cell polarity are crucial determinants of tissue morphogenesis and tissue architecture. They couple intercellular communication to cell identity, shape, migration, and asymmetric versus symmetric division. We ask through which mechanisms intercellular adhesion and polarity regulate the establishment and maintenance of epithelia, and aim to unravel key regulatory steps by which alterations in these proteins contribute to pathogenesis. We focus mainly on the stratifying epithelia of the skin using transgenic and conditional mouse models as well as cells isolated from these models. We have identified a crucial role for classical cadherins in skin barrier cohesion and function by regulating the formation of tight and adherens junctions and showed that they serve as important regulators of mammalian atypical protein kinase Cs (aPKCs) and the small GTpase Rac in the epidermal barrier and in tissue polarity pathways that regulate early morphogenetic movements. Epidermal aPKCι/λ disturbs epidermal barrier function and alters cell fate in the epidermis as a result of increased asymmetric divisions in stem and progenitor cell populations. This ultimately leads to loss of epidermal stem cells and premature skin aging. We furthermore identified epidermal insulin/insulin-like-growth-factor 1 (IGF-1) as major activators of Rac through which they determine asymmetric differentiation and proliferative potential of progenitors and thereby regulate epidermal differentiation and barrier function. Overall, our data suggest that regulation of cell architecture and metabolism are coupled and important for epidermal morphogenesis and homeostasis.

Host: Hans-Hermann Gerdes, Department of Biomedicine