Epithelial cells can develop various functional specializations, which are reflected in the organization and composition of the cytoplasm and in differentiations of the plasma membrane.
In most cases, these specializations are arranged in relation to the polarization of epithelial cells with respect to the apical and basal poles of the epithelium. Thus, epithelial cells have three domains: apical, facing the epithelial surface (which faces the external or internal environment or the lumen or secretory pole of the gland), lateral, which contacts neighboring cells, and basal, located close to the basement membrane.
Each of these regions has characteristic functional and morphological specializations, which are described below.
- Cilia and Flagella, which are mobile differentiations of the apical pole of lining cells. Cilia and flagella are formed by a cylindrical projection of the plasma membrane that surrounds a portion of cytoplasm containing a highly ordered microtubule cytoskeleton structure known as the axoneme. Cilia are distinguished from flagella by being shorter and straighter.
The axoneme is composed of ordered microtubules that run longitudinally within each cilium or flagellum. Typically, the axoneme contains a pair of central microtubules and nine peripheral doublets, with the latter being formed by a pair of fused microtubules, so they share a section of their wall. Extending from each of the peripheral doublets are a pair of dynein arms toward the next doublet, all directed in the same direction.
The axoneme is anchored at its basal part to a centriole, known as the basal body, so that the peripheral doublets of the axoneme are a continuation of the internal microtubules of the centriole triplets. The central pair of the axoneme originates at the basal plate of the cilium.
When present in large numbers, cilia can be observed under light microscopy, forming a brush border, which allows for the clear identification of ciliated epithelia.
- Microvilli, formed by cylindrical evaginations of the apical plasma membrane, which include a specialized zone of the cytoplasm containing abundant actin microfilaments. The apical cytoplasm of cells with numerous microvilli often contains a profuse network of tonofilaments, forming the terminal web.
In some epithelia, numerous short and straight microvilli are found, arranged tightly and in parallel. Under light microscopy, they appear as a refractile and striated border, known as the striated border. In other cases, long and flexible microvilli with a wavy appearance are present, known as stereocilia.
The main function of microvilli is to increase the surface area of the plasma membrane available for the transport of substances across epithelial cells. However, they are also contractile and facilitate the mobility of duct contents, such as in the gonoducts. They are also found in cells whose apical pole is sensory, with the microvillus membrane containing receptors for sensory stimuli.
- Microvilli, which are short, laminar, and rigid evaginations of the apical pole of epithelial lining cells. These apical microfolds are thought to have a hydrodynamic function, facilitating the reduction of friction between the apical pole of the epithelium and the fluid it comes into contact with (e.g., water or blood).
- Glycocalyx, which consists of a layer rich in mucopolysaccharides and glycoproteins, originating from the secretion of the epithelial lining cells themselves and exocrine glands, covering the apical surface of the epithelium.
The glycocalyx is often associated with the microvilli of the intestinal epithelium, containing digestive enzymes.
Due to its high carbohydrate content, the glycocalyx can be demonstrated with histochemical reactions such as the periodic acid-Schiff (PAS) reaction or ultrastructurally with heavy metal salts like ruthenium red.
- Intracellular Canaliculi, formed by invaginations of the apical plasma membrane toward the basal zone of the cell, but without penetrating the cytoplasm (although in non-medial sections, they appear surrounded by the cytoplasm). The invaginations of the plasma membrane have a wavy surface, giving their lumen a starry appearance. This lumen is continuous with the extracellular space.
The membrane of these canaliculi presents numerous branches, which approach tubules and cisterns of the smooth endoplasmic reticulum and the Golgi apparatus, collectively forming the tubulo-vesicular system. Numerous mitochondria are also associated with this system.
Intracellular canaliculi are related to increasing the surface area available for active ion transport from the internal to the external environment. Therefore, they are found in specialized epithelial cells involved in this activity, such as the parietal cells (oxyntic) of the gastric fundic glands in mammals and chloride cells (ionocytes) in some teleost fish.
- Intercellular junctions, which maintain adhesion and communication between adjacent epithelial cells and regulate permeability across the epithelium. They are classified into:
- Tight junctions (or occluding junctions), which are located near the apical pole, forming a belt around the cells, where the outer faces of adjacent plasma membranes fuse along a continuous reticular path, leaving adjacent spaces where the membranes do not fuse. This type of junction seals the intercellular space against the passage of high molecular weight substances.
- Adherens junctions, which are located immediately below the tight junctions and also form a peripheral belt in which the plasma membranes are separated by a constant-width intercellular space. The internal surfaces of both membranes show a deposit of electron-dense material, to which numerous microfilaments are anchored.
- Desmosomes (or adhering junctions), which ultrastructurally appear as plates formed by areas where the opposing membranes have condensations of electron-dense material on their cytoplasmic face. Tonofilaments (intermediate filaments of cytokeratins) arranged perpendicular to the membranes are anchored to these plates. The membranes follow a parallel course, leaving a slightly widened intercellular space containing a deposit of electron-dense material. They are sometimes distinguishable by light microscopy as "spines or intercellular bridges" in stratified epithelia.
- Gap junctions (nexuses or tight junctions), formed by punctate areas where the plasma membranes of adjacent cells come close together, narrowing the intercellular space but without fusion. The intercellular space is occupied by discrete deposits of electron-dense material that traverse it and penetrate the plasma membranes. These junctions are zones of intercellular communication, presenting low electrical resistance and allowing the exchange of various substances between cells.
It is common to find an ordered arrangement of intercellular junctions in the apicolateral region of epithelia, collectively forming a junctional complex or terminal bar (this term comes from the observation of the entire complex under light microscopy). A junctional complex includes, from apical to basal regions, a zonula occludens, a zonula adherens, and a variable number of desmosomes.
- Interdigitations, which comprise folds of the plasma membrane and cytoplasm of adjacent cells. These interdigitations increase the surface area of the cell membrane available for intercellular junctions, primarily desmosomes.
- Lateral or basolateral labyrinth, formed by numerous interdigitations between the evaginations of epithelial cells (plasma membrane and cytoplasm), which are thin and tortuous. The region of the cytoplasm from which the evaginations originate contains abundant mitochondria.
Functionally, the lateral or basolateral labyrinths are similar to the invaginations that give rise to the striated basal pole and serve to facilitate the active transport of products, primarily ions, mediated by membrane-associated transporters.
At the basal pole of epithelia, two types of specializations can be found:
- Hemidesmosomes, which form cell-matrix intercellular junctions. They are found in the plasma membrane of the basal pole of epithelial cells, adjacent to the lucid lamina, which is part of the basement membrane of the epithelium. They correspond to the structure of a half-desmosome, consisting of a plate of electron-dense material adjacent to the cytoplasmic face of the membrane. Bundles of tonofilaments anchor to this plate.
- Striated basal pole, which is formed by numerous invaginations of the plasma membrane at the basal pole, arranged in parallel and including areas of the cytoplasm rich in elongated mitochondria. These invaginations increase the membrane surface available for active transport of substances.
When present in large numbers, these invaginations are visible under light microscopy as basal striations, characteristic of epithelia involved in the active transport of substances.
This is a specialization of epithelial cells, called keratinocytes, in the stratified epithelia of vertebrates, primarily those that form the epidermis.
Keratinization involves the accumulation of keratins (of the α or β classes), in the form of intermediate microfilaments made of cytokeratins, and other proteins in the cytoplasm, as well as the release of lipids into the intercellular space, which collectively harden and waterproof the epithelium. As keratinocyte differentiation progresses, keratinization gradually increases from the germinative stratum to the apical stratum.
In the most extreme case, keratinization is referred to as cornification. This process includes the formation of a stratum corneum, which creates a dry and impermeable layer over the epithelium. The stratum corneum can be flexible, as in most of the epidermis of mammals, or rigid, as in the macro-scales of reptiles and birds or in the nails, claws, and horns of mammals. The corneal layer includes one or more layers of cornified scales resulting from the cornification of keratinocytes.
During the cornification process, keratinocytes accumulate tonofilaments and adhesive proteins (filaggrin, loricrin, involucrin) in the cytosol, which group together to form masses that become visible under the light microscope as basophilic structures called keratohyalin granules (they are not true granules as they are not surrounded by a membrane). They also accumulate lipids in the form of lamellar organelles (Odland bodies), which are exocytosed into the intercellular space to waterproof it and contribute to the adhesion between cornified scales.
As cornification progresses, keratinocytes gradually flatten, die, and their nucleus dissolves in the cytoplasm, forming the scales that eventually become part of the stratum corneum. These dead cells are shed either continuously (as in the epidermis of mammals) or cyclically (as in the scales of reptiles).