FIGURE 1.

Squamous lineage transcription factors (TFs) control skin epithelia form, function and diseases. (A) The stratified skin epidermis is composed of several epithelial layers, including the basal layer, harbouring epidermal stem cells (EpdSCs), suprabasal spinous and granular layers, and the stratum corneum (left). Skin blistering diseases occur when the epidermal adhesions and junctions are compromised, and barrier defects originate from disruptions of the stratification programme, including genes of cross-linking enzymes, cornified envelop and lipid metabolism. A common non-melanoma skin cancer, cutaneous squamous cell carcinoma (cSCC), arises from the skin epithelium and mimics wounds that never heal. (B) p63 maintains EpdSC proliferation and prevents precocious stratification by antagonizing p53, cell cycle inhibitors, 14-3-3σ, Notch, IKKα and activating miR-205. (C) p63 also regulates the expression of many cell adhesion and junction components, including Perp (desmosome), claudin (tight junction), keratins (intermediate filaments), integrins (adherens junctions), laminins (basement membrane), and Fras1 and Frem1/2 (extracellular matrix). (D) Squamous lineage TFs are p63 targets and join p63 to regulate epidermal stratification; many of these TFs are deregulated in congenital ectodermal conditions and skin inflammatory and malignant diseases