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Epidermal Growth and Differentiation at a Glance
  • The interfollicular epidermis is maintained by a population of stem cells.
  • Slow-cycling stem cells give rise to transit amplifying cells, which yield terminally differentiated cells.
  • Abnormalities in epidermal stem cells may be involved in pathogenesis of skin cancers and other proliferative epidermal diseases.
  • Epidermal differentiation is accompanied by orchestrated expression of keratins and subunits of cornified envelope.
  • Keratins contribute to the mechanical stability and pliability of the epidermis.
  • Mutations in major epidermal differentiation products are underlying causes of important skin diseases.

Although thin, human skin is a marvelously resilient and multifunctional organ. It performs immunomodulatory and thermoregulatory functions, is involved in social, cultural, and reproductive behaviors, and provides broad protection against water loss and environmental insults such as trauma, infection, and exposure to radiation or chemicals. The outermost layer of skin, termed the epidermis, consists of a stratified squamous epithelium and its appendages, including hair follicles, sebaceous, apocrine, and eccrine glands. This chapter discusses epidermal differentiation, with the primary focus placed on keratin filaments that are formed as major structural elements within the epidermis. Defects in epidermal keratins are known to play key roles in a number of important blistering epidermal diseases. Additional major epidermal differentiation markers, including keratohyalin granules and the cornified envelope, are also discussed.

Keratins and Their Classification

Keratins (also known as cytokeratins) are structural proteins that belong to the superfamily of intermediate filament (IF) proteins. They are heterogeneous in size (40–70 kDa) and charge (pI 4.7–8.4), and notoriously insoluble. Sequencing the human genome revealed the presence of 54 functional keratin genes that are nearly perfectly conserved in other mammals.1 The tremendous diversity of keratin genes had not been fully appreciated until the advent of database mining and genomics, and could not be accommodated in the original nomenclature system aptly devised by Roland Moll, Werner Franke and colleagues in 1982.2 In 2006, an international effort culminated in a revised nomenclature (Table 46-1) that accommodates the newly discovered keratins, adheres to the guidelines of the Human and Mouse Gene Organization Gene Nomenclature Committee, and maintains the original designation of keratins devised by Moll and colleagues.1

Table 46-1 Human Keratins and Their Distributiona

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