Epithelial Skin Biology: Three Decades of Developmental Biology, a Hundred Questions Answered and a Thousand New Ones to Address

Abstract

The mammalian skin epidermis and its hair and sweat gland appendages provide a protective barrier that retains essential body fluids, guards against invasion by harmful microbes, and regulates body temperature through the ability to sweat. At the interface between the external environment and the body, skin is constantly subjected to physical trauma and must also be primed to repair wounds in response to injury. In adults, the skin maintains epidermal homeostasis, hair regeneration, and wound repair through the use of its stem cells. This essay focuses on when stem cells become established during skin development and where these cells reside in adult epithelial tissues of the skin. I explore how skin stem cells maintain tissue homeostasis and repair wounds and how they regulate the delicate balance between proliferation and differentiation. Finally, I tackle the relation between skin cancer and mutations that perturb the regulation of stem cells.

Keywords: Cancer; Epithelial; Hair follicle; Skin development; Stem cell; Stem cell niche; Sweat gland; Transcriptional regulation; WNT signaling.

Figure 1

Schematic of the resting and growth phases of the hair follicle. The stem cells (purple) reside in the outer layer of the bulge niche, which anchors the hair from the previous hair cycle. The bulge cells at the base are referred to as the hair germ, which during telogen, is abutted next to the dermal papilla (DP), the mesenchymal stimulus of the hair follicle. Following a buildup of BMP inhibitors (Noggin) in the DP and WNTs in the hair germ, the stem cells at the base are activated and generate the short-lived progeny (orange), which ultimately will differentiate into the hair and its channel. This figure is patterned after Figure S5 in Hsu, Li, and Fuchs (2014b). Elsevier Press.

Figure 2

Immunofluorescence images showing a resting phase hair follicle, replete with bulge stem cells and keratin 6+ inner bulge nonstem cells. At left, bulge and hair germ cells are label-retaining and marked by H2B-GFP used in a pulse-chase labeling experiment. At right, bulge is labeled with GFP driven by a HF stem cell-specific super-enhancer epicenter element. Left panel is Figure 5 Frame C of Hsu et al. (2011). Elsevier Press. Right panel is Figure 2e of Adam et al. (2015). Nature Press.

Figure 3

Semi-thin section and ultrastructure of a sweat gland from the mouse paw pad. The gland is a bilayered epithelium consisting of myoepithelial and luminal epithelial cells. The duct opens out onto the surface of the epidermis. This figure is courtesy of H.A. Pasolli.