Granular Layer , Cornified Layer & The Regulation of Epidermal Proliferation and Differentiation

Granular Layer

The most superficial layer of the epidermis containing living cells, the granular layer or stratum granulosum, is composed of flattened cells holding abundant keratohyaline granules in their cytoplasm. These cells are responsible for further synthesis and modification of proteins involved in keratinization (Chu, 2008). The granular layer varies in thickness in proportion to that of the overlying horny cell layer. For example, under thin cornified layer areas, the granular layer may be only 1–3 cell layers in thickness, whereas under the palms of the hands and soles of the feet the granular layer may be 10 times this thickness. A very thin or absent granular layer can lead to extensive parakeratosis in which the nuclei of keratinocytes persist as the cells move into the stratum corneum, resulting in psoriasis (Murphy, 1997). The keratohyaline granules are deeply basophilic and irregular in shape and size, and they are necessary in the formation of both the interfibrillary matrix that holds keratin filaments together and the inner lining of the horny cells. Enzymatic action of the keratohyaline granules results in the production of “soft” keratin in the epidermis by providing periodic cutting of keratin filaments. In contrast, the hair and nails do not contain keratohyaline granules, and the tonofibril filaments traversing the cell cytoplasm will harden because of the incorporation of disulfide bonds, producing “hard” keratin in those structures (Matoltsy, 1976; Schwarz, 1979). Lysosomal enzymes present only in small amounts in the stratum basalis and stratum spinosum are found at high levels in the stratum granulosum because the granular layer is a keratogenous zone of the epidermis. Here, the dissolution of cellular organelles is prepared as the cells of the granular layer undergo the abrupt terminal differentiation process to a horny cell of the cornified layer (Chu, 2008).

Cornified Layer

Horny cells (corneocytes) of the cornified layer provide mechanical protection to the underlying epidermis and a barrier to prevent water loss and invasion by foreign substances (Jackson, Williams, Feingold, & Elias, 1993). The corneocytes, which are rich in protein and low in lipid content, are surrounded by a continuous extracellular lipid matrix (Chu, 2008). The large, flat, polyhedral-shaped horny cells have lost their nuclei during terminal differentiation and technically are considered to be dead (Chu; Murphy, 1997). The physical and biochemical properties of cells in the cornified layer vary in accordance with position in order to promote desquamation moving outward. For instance, cells in the middle have a much higher capacity for water-binding than the deeper layers because of the high concentration of free amino acids found in the cytoplasm of middle layer cells. The deep cells also are more densely compact and display a greater array of intercellular attachments than the more superficial layers. Desmosomes undergo proteolytic degradation as the cells progress outward, contributing to the shedding of corneocytes during desquamation (Haake & Hollbrook, 1999).

The Regulation of Epidermal Proliferation and Differentiation

As a perpetually regenerating tissue, the epidermis must maintain a relatively constant number of cells as well as regulate the interactions and junctions between epidermal cells. Adhesions between keratinocytes, the interactions of keratinocytes and immigrant cells, the adhesion between the basal lamina and the underlying dermis, and the process of terminal differentiation to produce corneocytes must be regulated as cells relocate during development as well as throughout life (Haake & Hollbrook, 1999). Epidermal morphogenesis and differentiation is regulated in part by the underlying dermis, which also plays a critical role in the maintenance of postnatal structure and function. The epidermal-dermal interface is also a key site in the development of epidermal appendages. The maintenance of a constant epidermal thickness depends also on intrinsic properties of epidermal cells, such as the ability to undergo apoptosis, programmed cell death. Apoptosis follows an orderly pattern of morphologic and biochemical changes resulting in cell death without injury to neighboring cells, as is often the case in necrosis. This major homeostatic mechanism is regulated by a number of cellular signaling molecules including hormones, growth factors, and cytokines. In the skin, apoptosis is important in developmental remodeling, regulation of cell numbers, and defense against mutated, virus-infected, or otherwise damaged cells. Terminal differentiation is a type of apoptosis evolved to convert the keratinocyte into the protective corneocyte (Haake & Hollbrook, 1999). The disruption of dynamic equilibrium maintaining constant epidermal thickness can result in conditions such as psoriasis, whereas the dysregulation of apoptosis is often seen in tumors of the skin (Kerr, Wyllie, & Currie, 1972).