Research

• Our Main Objectives
• Introduction to Keratin Genes and Proteins
• Assembly and Organization of Keratin Filaments
• Keratins fulfill Multiple Roles in Skin and other Epithelia
• Keratin Gene Expression in Epidermis: Basic Principles and Disease Associations
• Introduction to Skin Epithelia
• Figure 1 - Introduction to Keratins
• Table 1 - Keratin-based, Inherited Skin Bullous Disease Affecting Primarily the Epidermis

Generalities about Skin Epithelia

Adult skin features several complex epithelia which, while distinct in their architecture and function, are all derived from the developing embryonic ectoderm. Together these epithelia contribute significantly to several of the key functions of skin tissue as a whole, including permeability barrier, protection against UV irradiation, sensory perception, immunological surveillance, thermoregulation, and defence (in wild animals).

The major components of skin epithelia are the epidermis, the hair follicle and their associated glands (known as pilosebaceous units), the nail, and eccrine sweat glands. Among these epithelia the epidermis is probably the best understood. The polarity of epidermis reflects a functional compartmentation, with progenitor cells attached to the basal lamina at the base of the tissue, and terminally differentiated cells in the superficial layers of the tissue. Four distinct layers are recognized based on morphological criteria on histological cross-section: the basal, spinous, granular, and stratum corneum layers. The uppermost stratum corneum layer is responsible for the barrier function. It takes ~2-4 weeks for a keratinocyte to complete the program of terminal differentiation in human trunk epidermis. A vast number of genes are involved in the execution of this program over this long time period. Our understanding of the molecular mechanisms that control the balance between proliferation and differentiation in epidermis, as well as those controlling the execution of differentiation, is fair but incomplete. Likewise, relatively little is known about the mechanism(s) enabling the epidermis (of a given body site) to maintain a uniform thickness throughout life. As suggested by its histology, there is a built-in synchrony in the epidermis that implies the existence of a tremendous degree of communication and coordination between adjacent cells, as well as between non-adjacent "layers".

Hair follicles, nail, sebaceous, and sweat glands are appendageal structures made up of epithelia which, albeit somewhat related in their basic properties (e.g., functional organization; homeostasis), are distinct from epidermis. In the hair follicle alone, there are eight distinct programs of terminal differentiation being executed during growth. Throughout life, hair follicles undergo a complex cycle featuring phases of growth, involution, and rest. In the specialized literature these are referred to the anagen, catagen, and telogen stages, respectively. In hairy skin (all body sites except foot, sole, eyelid), the totipotential stem cells for skin epithelia are believed to reside at or near the bulge, a "thickening" of the hair follicle outer root sheath that occurs near the point of insertion of the arrector pili muscle. The cellular origin of most nonmelanoma skin tumors lies in the hair follicle. How this relate to the epithelial stem cell population(s) remains to be ascertained. Significant progress has been made in recent years towards the identification of some of the signaling mechanisms that underlie the transition between the various phases of the hair cycle. Considerably less is known about the homeostasis of glandular epithelia.

These various epithelial compartments lie over, or in some cases are embedded within, a connective tissue known as the dermis. Through its rich vascularization and innervation and a complex extracellular matrix, the dermis makes essential contributions to the properties and functions of skin. The regulation of cutaneous blood flow represents an important homeostatic mechanism for the regulation of body heat, and the afferent and efferent innervation of the skin are an integral part of sensory perception. The dermis is also the source of instructions that play essential roles in the morphogenesis and the homeostasis of mature skin tissue.

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