The cornified envelope: a model of cell death in the skin

Abstract

The epidermis functions as a barrier against the environment by means of several layers of terminally differentiated, dead keratinocytes - the cornified layer, which forms the endpoint of epidermal differentiation and death. The cornified envelope replaces the plasma membrane of differentiating keratinocytes and consists of keratins that are enclosed within an insoluble amalgam of proteins, which are crosslinked by transglutaminases and surrounded by a lipid envelope. New insights into the molecular mechanisms and the physiological endpoints of cornification are increasing our understanding of the pathological defects of this unique form of programmed cell death, which is associated with barrier malfunctions and ichthyosis.

Analysis of the individual and aggregate genetic contributions of previously identified serine peptidase inhibitor Kazal type 5 (SPINK5), kallikrein-related peptidase 7 (KLK7), and filaggrin (FLG) polymorphisms to eczema risk

“…Filaggrin is a key protein for the development of the cornified envelope and the process of cornification 53 . Two common null mutations in the FLG gene (R501X, 2282del4) have been firmly established as strong risk factors for eczema 22,23 .…”

p63 in epithelial development

“…The epidermis is continuously regenerated by mitotically active keratinocytes that reside in the inner basal layer and which, following detachment from the basement membrane, migrate to the outer cornified layer (terminal differentiated compartment): this process is called cornification [1]. The epidermis is continuously renewed due to a regulated balance between proliferation and differentiation.…”

AKT1-mediated Lamin A/C degradation is required for nuclear degradation and normal epidermal terminal differentiation

“…Nuclear degradation is a key stage in keratinocyte terminal differentiation and the formation of the cornified envelope that comprises the majority of epidermal barrier function. [1][2][3] Parakeratosis, the retention of nuclear material in the cornified layer of the epidermis, is a common histological observation in many skin diseases, but most notably in the epidermal barrierdefective diseases eczema and psoriasis. 4,5 Mechanisms of nuclear degradation in the epidermis have not yet been well characterised and it is not known whether the retained nuclei contribute to the altered epidermal differentiation programmes seen in these skin diseases.…”