Role of β-catenin in Epidermal Stem Cell Expansion, Lineage Selection, and Cancer

the body and the environment. The main epidermal cell type is an epithelial cell, the keratinocyte.The major structures of the epidermis are the interfollicular epidermis (IFE), hair follicles (HFs), sweat glands, and sebaceous glands (SGs). In human epidermis, the sweat glands are present in both hair-bearing and hairless regions, whereas in mouse epidermis, the sweat glands are restricted to the paws. Because most in vivo studies are performed on the mouse, we will not refer to the sweat glands further in this chapter (Fig. 1). To fulfill their functions, keratinocytes within the epidermis undergo terminal differentiation, resulting ultimately in cell death. Thus, the outermost, cornified, layers of the IFE, which form a physical barrier to penetration by microorganisms and prevent water loss, are anucleate cells filled with heavily cross-linked proteins and lipids. The cells of the hair shaft are also dead cells that are replaced during the hair growth cycle. Furthermore, during terminal differentiation, SG cells burst, releasing their lipid content onto the hairs and the surface of the skin to provide lubrication. Because the terminally differentiated cells of the epidermis are dead cells and are continually shed from the skin surface, it was appreciated many decades ago that the tissue must be maintained by proliferation of less-differentiated cells that both replenish themselves and the terminally differentiated cells. Thus, the epidermis is one of the tissues in which it has long been acknowledged that there resides a stem cell compartment (Hall and Watt 1989). Our current view is that there are distinct pools of stem cells in discrete locations within the HF, IFE, and SG Role of β-catenin in Epidermal Stem Cell Expansion, Lineage Selection, and Cancer