Overview of epidermal differentiation and cornification.
The epidermis consists of layers of keratinocytes at different stages of differentiation. Basal keratinocytes, distinguished by the expression of keratins 5 and 14, proliferate, producing new cells that will differentiate while passaging towards the skin surface. Cells of the spinous layer enter cell cycle arrest. They express typical markers of differentiation such as keratins 1 and 10, and caspase-14. NF-κB expression is also increased, inhibiting apoptosis. Pro-filaggrin and proteins of the epidermal differentiation complex are expressed as cells transition from the spinous to the granular layer. Cornification is initiated from the granular layer. Caspase-14 becomes active and contributes to the processing of filaggrin, and various anti-inflammatory proteins are expressed. Lamellar bodies are extruded, releasing serine proteases and lipids that will fill the inter-corneocyte space. Rapid intracellular acidification enables degradation of the nucleus and other organelles, at which point the cells would be considered dead. Keratins and other proteins are cross-linked by transglutaminases forming the cornified envelope. Eventually, proteases degrade the corneodemosomes that hold the corneocytes together allowing the cells to shed during desquamation.