Cornification Diseases (Skin Cell Death)

Abstract

Abstract The outermost layer of the skin is formed by the cornified envelope (CE), which is the end product of the process of keratinization. This forms a barrier that is essential to protect the internal homeostasis of the organism from the external environment. The process of keratinization proceeds according to a complex and elaborately controlled differentiation program with the coordinated expression of genes encoding specialized components, enzymes, and regulatory molecules. The CE is a specialized structure that replaces the plasma membrane of differentiating keratinocytes and consists of proteins crosslinked by covalent bonds and lipids to form a scaffold. Understanding of the pathologies associated with defects in CE components will help clarify the molecular mechanisms and the physiological endpoints of keratinization. Here, we describe some diseases of keratinization, and give a brief overview on animal models (transgenic and knockout) with defects in the CE formation. Key concepts: The outermost layer of the skin is formed by the cornified envelope (CE). The CE is a specialized structure that replaces the plasma membrane of differentiating keratinocytes. It consists of proteins crosslinked by covalent bonds and lipids to form a scaffold. The CE is essential to provide the barrier function of the epidermis. The transglutaminase enzymes play a major role in the formation of the CE by catalyzing the formation of crosslinks between specific proteins. Mutations in keratin genes cause a wide variety of epidermal and other epithelial disorders. CE lipids contribute in a significant way to the establishment of barrier function of the epidermis by impermeabilizing the cornified cell and participating in the organization of the intercellular lipid lamellae. Defects in proteases result in barrier function abnormalities or skin diseases. The transcription factor p63 is crucial in epidermis formation, maintaining the progenitor‐cell populations that are necessary to sustain epithelial development and morphogenesis.