Stratum corneum keratinocyte terminal differentiation

FIGURE 2.2 A diagram of human skin. Epidermal thickness depends upon body site being thickest on the palms and soles (-1500 pm) and thinnest around the eyes (-10 pm). The stratum corneum is the only layer composed of anucleated, terminally differentiated kerati-nocyte cells called corneocytes. All other epidermal layers contain nucleated keratinocytes. The dermis is composed primarily of the structural proteins collagen and elastin. 

The stratum corneum consists of denucleated corneocytes filled with cross-linked proteins, while the intercellular space is occupied by lipids synthesized prior to and during cornification [24], Formation of this barrier relies on the cornification of epidermal keratinocytes, which undergo growth arrest, terminal differentiation, and an epidermal-specific cell death, referred to as planned cell death [25], Abnormalities in any of these programmed events may lead to epidermal disorders such as psoriasis, atopic dermatitis, and cancer. Flowever, biological events that enable basal cells (stem cells) to proliferate, differentiate, and commit planned cell death are still poorly understood [10]. The keratinocyte differentiation process can be stimulated by prodifferentiation agents such as extracellular calcium and 1,25-dihydroxy cholecalciferol (referred to as vitamin D3 hereafter) [23], Aberrant or absent differentiation can be found in other skin disorders such as atopic keratosis, seborrheic keratosis, and rosacea. 

The remarkable barrier function of the skin is primarily located in the stratum corneum (SC), the thin, outermost layer of the epidermis. The SC consists of several layers of protein-filled corneocytes (i.e., terminally differentiated keratinocytes) embedded in an extracellular lipid matrix. Attached to the outer cor-neocyte envelope are long-chain covalently bound cer-amides that interact with the lipids of the extracellular space. These lipids are composed primarily of free fatty acids, ceramides, and cholesterol arranged in multiple lamellae.f Passive permeation across the SC is believed to occur primarily via the intercellular... 

Terminally differentiated keratinocytes of the stratum corneum are known as comeocytes and are largely devoid of normal cellular functions, being predominantly composed of protein (keratin). The ultrastructure of the stratum corneum is described by the brick and mortar model (Elias, 1983 Figure 3). The functional implication of this architecture is that some skin penetrants must diffuse via a long and tortuous route between adjacent comeocytes, thus reducing their rate of absorption. This is known as the intercellular route. In contrast, some chemicals may diffuse equally through both comeocytes and the lipid mortar, resulting in a transcellular route. 

---