The epithelium is the first tissue to develop during phylogenesis and ontogenesis; the evolutionary appearance of modern epithelia reflects the requirement of Metazoa for a tissue structure that can segregate their internal medium from the outside environment.
Epithelial cells form tight monolayers with an apical junctional complex, which segregate apical and basolateral plasma membrane domains with different lipids and protein composition that are required to act as active barriers between the body and the environment.
In higher vertebrates there are more than 150 different types of epithelia that form the key functional components of most body organs; in part because of their exposure to external noxa, epithelia are the main sources of cancer and other human diseases.
The epithelial phenotype can be lost and acquired during development through mechanisms called epithelial–mesenchymal transition (EMT) and mesenchymal–epithelial transition (MET), respectively; a process similar to EMT might account for dissemination of cancers, which, in humans, arise mainly from epithelial cells.
The acquisition and maintenance of the epithelial phenotype is guided by an epithelial polarity programme (EPP), which is regulated by a network of polarity proteins and lipids; although these regulators have been highly conserved during evolution, the execution of the EPP is highly variable and context dependent.
The EPP proteins and lipids organize themselves into primordial apical and basolateral domains in response to external cues from other cells and the substratum; execution of the EPP results in the formation of the apical junctional complex, the reorganization of the cytoskeleton and the secretory and endosomal organelles in order to generate apical–basal polarity required for vectorial transport functions.
Epithelial cells require apical–basal plasma membrane polarity to carry out crucial vectorial transport functions and cytoplasmic polarity to generate different cell progenies for tissue morphogenesis. The establishment and maintenance of a polarized epithelial cell with apical, basolateral and ciliary surface domains is guided by an epithelial polarity programme (EPP) that is controlled by a network of protein and lipid regulators. The EPP is organized in response to extracellular cues and is executed through the establishment of an apical–basal axis, intercellular junctions, epithelial-specific cytoskeletal rearrangements and a polarized trafficking machinery. Recent studies have provided insight into the interactions of the EPP with the polarized trafficking machinery and how these regulate epithelial polarization and depolarization.
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Research in E.R.B.'s laboratory was supported by US National Institutes of Health (NIH) grants EY08538, EY022165 and GM34107, and by the Dyson, Research to Prevent Blindness, Beckman and Starr Foundations. Research in I.G.M.'s laboratory was supported by NIH grants CA132898 and GM50526, and by a grant from the Susan Komen Breast Cancer Foundation.
The authors declare no competing financial interests.
Refers to the evolutionary history of species. Embryo development reflects the course of evolution, partially supporting Hackel's proposal that ontogenesis recapitulates phylogenesis; however, the more generalized form of this concept has been mostly discredited.
- Polarized trafficking machinery
The special configuration that has been adopted by the secretory pathway and endosomes in polarized epithelia cells.
The origin and development of an organism from the fertilized egg to mature form.
- Primary cilium
A protrusion at the free surface of most interphase vertebrate cells that disassembles during mitosis. It is based on nine pairs of microtubules that emerge from a basal body. It houses a number of signalling pathways that are important for development, such as Hedgehog.
- Planar polarity
The polarization of epithelial cells along the plane of the epithelium (orthogonal to the apical–basal axis), which directs the orientation of cell shape, division, movement and differentiation. Non-epithelial cells can also exhibit planar polarity.
- Epithelial–mesenchymal transition
(EMT). A developmental programme during which epithelial cells adopt a mesenchymal phenotype that is marked by the loss of intercellular adhesion and by increased cell migration. During EMT, markers such as epithelial cadherin (E-cadherin), Crumbs and cytokeratins are downregulated, whereas mesenchymal markers such as vimentin are upregulated.
(Madin Darby canine kidney). A polarized epithelial cell line that is widely used for the study of polarity, membrane trafficking and cell adhesion.
- Apical–basal polarity
The polarity axis along the apical (uppermost) and basal plasma membrane domains. In epithelial cells the two plasma membrane domains have different protein and lipid composition, which are required to carry out directional transport of nutrients and waste between the two sides of the epithelium.
- Basement membrane
The condensation of extracellular matrix components (collagens, laminins, distroglycans, elastins and others) that are secreted partly by epithelial cells and underlie connective tissue and vascular cells, to which epithelial cells attach through integrin receptors.
Transmembrane proteins composed of two (α- and β-) subunits that link the actin cytoskeleton with extracellular components such as the basement membrane.
- Front–rear polarity
A morphological characteristic of migratory cells wherein the front (leading edge) and the rear (uropod) show morphological and functional asymmetry.
- Apical junctional complex
A belt-like structure at the border between apical and lateral domains that are formed by adherens junctions with a predominantly adhesive function and tight junctions (septate junctions in invertebrates) with a predominantly sealing role. Both junctions are formed by adhesive transmembrane proteins (claudin and occludin for tight junctions and E-cadherin for adherens junctions) and cytoplasmic 'plaque' proteins that link these junctions with the actin cytoskeleton.
Small plasma membrane protrusions at the surface of cells that increase the surface area and facilitate absorption and secretion.
- Clathrin-mediated endocytosis
Formation of some types of endocytic vesicles at the plasma membrane, which is mediated by clathrin and clathrin adaptors such as adaptor protein 2 (AP-2).
Small vesicles that are released from cells by fusion of multivesicular bodies with the plasma membrane. They have multiple communication roles between cells.
- Microtubule motors
A family of plus end and minus end directed kinesins and minus end directed dyneins that move transport vesicles and organelles along the cytoskeleton and across the viscous cytoplasm using ATP as an energy source.
A highly conserved octameric protein complex, which is part of a large group of 'tethering factors', that regulates the docking and fusion of transport vesicles with the plasma membrane.
Proteins that regulate secretory vesicle fusion.
- Coat protein
Eukaryotic cells express coatomer protein and the clathrin family of coat proteins; they fold membranes to generate transport vesicles in cooperation with adaptors selecting specific cargo proteins that will be passengers during the transport to a different membrane.
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Rodriguez-Boulan, E., Macara, I. Organization and execution of the epithelial polarity programme. Nat Rev Mol Cell Biol 15, 225–242 (2014). https://doi.org/10.1038/nrm3775
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