Fig. 2

Skin architecture and Notch pathway member distribution. (Left panel) Organization of human skin. The epidermis is the thinnest and most superficial layer of the skin, it is connected to the underlying dermis through the cutaneous basement membrane zone (BMZ), the highly specialized structure which connects the epidermis to the dermis ensuring skin integrity and stability against mechanical insults. Epidermis is arranged into four distinct layers: basal, spinous, granular and stratum corneum (or horny layer). The deepest layer of the epidermis, overlaying the BMZ, is the basal layer which is followed by the spinous and the granular layers whilst the stratum corneum is the outermost. Each layer is typified by keratinocytes (KCs) at various stages of differentiation. KCs of the basal layer are characterized by their ability to proliferate. Indeed, in the basal layer, epidermal stem cells (SCs) divide to self-renew and produce transient amplifying cells (also known as committed progenitors—CPs), which possess a more limited proliferation capability. In the early phases of differentiation, CPs detach from the BMZ and move toward the stratum corneum becoming terminally differentiated cells (TDs) devoid of nuclei. (Right panel) Expression pattern of Notch receptors (NOTCH1-4) and Notch ligands (JAG1 and DLL1) in human skin [143, 144]