The cells are cuboidal to columnar in shape, with a large nucleocytoplasmic ratio. The cells adhere to the basement membrane via hemidesmosomes, and with their neighboring cell with desmosomes. Tonofilaments are prominently seen in the cytoplasm, radiating from the hemidesmosomes as well as desmosomes. Other cellular organelles such as ER, mitochondria, etc., are also seen at the ultrastructural level (Fig. 2.2). In pigmented skin, many melanosomes can be seen “capping” the nucleus of the cells of SB (Fig. 2.3). Basal cells are characterized by presence of Keratins 5 and 14.

The spinous or “prickly layer” is named so due to the large number of desmosomes that connect adjacent cells, and the prominent tonofilaments that radiate from the desmosomes. Several layers of cells are seen in this suprabasal layer. In histological preparations, large intercellular spaces (preparation artifacts) that are seen between the adjacent desmosomes gives this layer a distinct appearance. At the electron microscopic level of observation, large numbers of desmosomes mark this layer, and epidermal lamellar bodies begin to appear in the cytoplasm of cells. These organelles ranging from 0.2 to 0.5 μ size contain cholesterol, glycolipids, and fatty acids, in addition to a battery of enzymes and antimicrobial peptides. Thus the synthesis of proteins (Keratins 1 and 10) as well as lipids mark the progressive differentiation of the keratinocytes that move up being “pushed” by the newly proliferating cells below.

This layer is named for the presence of Keratohyalin granules that appear within the cells along with the flattening or elongation of the keratinocytes. Keratohyalin granules can be clearly identified in histological preparations (Fig. 2.1). With Electron microscopy, these granules appear irregularly shaped, and embedded within the keratin filaments. Immunoreactivity shows that they contain Profilaggrin, (whose breakdown product, Filaggrin is needed for aggregation of keratin filaments), Loricrin as well as Involucrin, two proteins that are important for the formation of the cornified envelope. Synthetic activities—both for structural proteins and barrier lipids—reach their peak at this layer. In the uppermost layer of SG, about 20 % of the cell volume is occupied by the epidermal lamellar bodies (LB), which are membrane bound structures containing stacked disc like contents. The discs can be compared to flattened liposomes, but they are actually more like pleated sheets—connected with each other (Fig. 2.4) folded like an accordion (Elias and Menon 1991). The LBs arise from the Trans-Golgi network, and remain interconnected with each other—forming a Lamellar body secretory system, positioned for secretion at a basal rate, or for a coordinated massive secretory response (Elias et al. 1998), when needed as following barrier disruption or at terminal differentiation of individual cells. As for proteins, during the process of terminal differentiation, the enzyme transglutaminase mediates the cross-linking of involucrin and loricrin, forming a thickened cornified envelope (CE) just inside of the plasma membrane. Profilaggrin is cleaved by proteases to produce filaggrin, which aggregates the keratin filaments. About the same time cellular organelles begin to get degraded through activity of proteases such as Caspases involved in the programmed cell death of keratinocytes. Thus the fully differentiated keratinocytes becomes corneocytes, the cells that make up the stratum corneum. Loss of function mutations in Filaggrins are now recognized as the basis of several skin dysfunctions ranging from sensitive skin/atopic dermatitis to several forms of Ichthyotic conditions termed disorders of cornification.(Irvine et al. 2011). In addition, tight junctions between the adjacent cells in outermost layer of SG add another barrier under the SC (Brandner 2009; Brandner and Proksch 2006)—and it is believed that they help in the polarized secretion of lamellar bodies. However, gene knock-out rodents for tight junction (TJ) proteins also fail to develop a functional permeability barrier, pointing to a highly significant role(s) of the TJs in the overall epidermal barrier formation (Proksch et al. 2008).

At this stage, the corneocyte is an extremely flattened (30–40 μ wide) and thin (about half a Micron in thickness) ghost of a cell filled with keratin bundles (Fig. 2.5). Further breakdown of Filaggrin leads to the production of a mixture of aminoacids collectively termed: natural moisturization factors (NMF) that allows each cell to hold moisture needed to plasticize the keratin within (Rawlings and Matts 2005). The secreted lamellar body contents, which fill the interstices of the corneocytes within the strata, undergo further catabolic modifications mediated by co-secreted enzymes, to give rise to an equimolar mixture of Cholesterol: Ceramides and fatty acids, (Fig. 2.6) which forms a lamellar structure (Wertz 2000) that occlude the intercellular space within SC—forming the permeability barrier. (Fig. 2.7). Thus, the SC is transformed to a “brick and mortar” like model—a composite material—displaying properties that are more than the sum of its components. During the terminal differentiation, desmosomes are also modified to “corneodesmosomes”: that make the corneocytes very cohesive, until the cells reach the outer most layers when programmed proteolysis of corneodesmosomes release individual cells or small units of cells that exfoliate from the surface. Such shedding of corneocytes signal the underlying cells to differentiate and join the SC-maintaining homeostasis/Autopoesis of the stratum corneum. (Hoath 2001) The number of cell layers in SC may be 10–18 cell layers varying with anatomic location. As the visible and terminally differentiated barrier layer (10 μm thick), it is often said that the SC stands between life and certain death. The characteristic, loose basket-weave appearance of this layer in histological preparations is indeed an artifact created during the dehydration and paraffin embedding protocol. Much research has been conducted on this layer, with an amazing array of techniques in the past 3 decades or so (see Elias and Feingold 2006) and what has emerged is a view that SC is not an inflexible brick wall, but an interactive boundary layer, sensing and responding to environmental changes like a “smart material” (Menon and Elias 2001). As the Stratum corneum is the perceived (oily, dry, pigmentary changes) and perceiving (touch, temperature) surface of skin it is literally and figuratively, the touch screen of the body.