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Apical–basal polarity and the control of epithelial form and function

Abstract

Epithelial cells are the most common cell type in all animals, forming the sheets and tubes that compose most organs and tissues. Apical–basal polarity is essential for epithelial cell form and function, as it determines the localization of the adhesion molecules that hold the cells together laterally and the occluding junctions that act as barriers to paracellular diffusion. Polarity must also target the secretion of specific cargoes to the apical, lateral or basal membranes and organize the cytoskeleton and internal architecture of the cell. Apical–basal polarity in many cells is established by conserved polarity factors that define the apical (Crumbs, Stardust/PALS1, aPKC, PAR-6 and CDC42), junctional (PAR-3) and lateral (Scribble, DLG, LGL, Yurt and RhoGAP19D) domains, although recent evidence indicates that not all epithelia polarize by the same mechanism. Research has begun to reveal the dynamic interactions between polarity factors and how they contribute to polarity establishment and maintenance. Elucidating these mechanisms is essential to better understand the roles of apical–basal polarity in morphogenesis and how defects in polarity contribute to diseases such as cancer.

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Fig. 1: Structure and functions of simple epithelia.
Fig. 2: Domain structure of the main epithelial polarity factors and their interactions.
Fig. 3: Regulation of aPKC activity by other apical polarity factors.
Fig. 4: Antagonistic interactions between polarity factors.
Fig. 5: Establishing polarity.
Fig. 6: Context-specific roles of Crumbs in morphogenesis.
Fig. 7: Polarity changes associated with tumour metastasis.

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Acknowledgements

D.St.J. is supported by a Wellcome Trust Principal Research Fellowship and C.B. by a Wellcome Trust/Royal Society Henry Dale Fellowship.

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Supplementary Information

Glossary

Basement membrane

A layer of extracellular matrix (ECM) between epithelia and other tissue layers.

Epithelial–mesenchymal transition

(EMT). The progressive and reversible loss of epithelial characteristics such as cell–cell adhesion and apical–basal polarity to form a migratory, mesenchymal cell with front–rear polarity.

Neural crest

A population of multipotent migratory cells originating from the dorsal neural tube of vertebrates. Neural crest cells give rise to diverse cell types, including peripheral nervous system cells such as cranial nerves, cartilage and bone.

Transepithelial resistance

The electrical resistance across an epithelium that indicates how well the tight junctions block the passage of ions from one side of the epithelium to the other. This measures the barrier function of the epithelium.

Follicular epithelium

A monolayered epithelium in Drosophila melanogaster encasing developing oocytes within the egg chambers.

WD40 protein

A protein containing multiple copies of the ~40 amino acid WD40 motif. WD40 motifs fold together to form a β-propeller structure.

MAGUK family proteins

Membrane-associated guanylate kinase (MAGUK) proteins are scaffolding proteins defined by the presence of an SH3 domain, one or more PDZ domains and a catalytically inactive guanylate kinase (GUK) domain.

RAS association domain-containing proteins

A family of proteins that contain an N-terminal Ras association domain with a ubiquitin-like fold that mediates protein–protein interactions, although not necessarily with Ras.

Planar cell polarity

(PCP). A polarity axis that aligns cells and cellular structures in the plane of the epithelium, perpendicular to the apical–basal axis.

Moesin

The sole member of the Ezrin, Moesin, Radixin (ERM) family of proteins in Drosophila. ERM proteins link the plasma membrane and transmembrane proteins to the cortical actin cytoskeleton.

Spectrin

α-Spectrins and β-spectrins form rod-like heterotetramers that bind actin and the plasma membrane to form a hexagonal cytoskeletal scaffold that supports the plasma membrane. In insects, α-spectrin and βH-spectrin tetramers form the spectrin cytoskeleton beneath the apical plasma membrane, whereas α-spectrin and β-spectrin tetramers underlie the basolateral membrane.

Hippo pathway

A signalling pathway in epithelia that regulates cell division and promotes apoptosis, therefore controlling tissue growth.

α-Catenin

A component of the E-cadherin adhesion complex that links the actin cytoskeleton to E-cadherin through β-catenin.

Katanin

A microtubule-severing protein that is a component of non-centrosomal microtubule organizing centres.

WDR62

A protein that localizes to non-centrosomal microtubule organizing centres and spindle poles.

Blastoderm

An early stage in insect development when the embryo is composed of a single layer of nuclei or cells surrounding a central yolk mass.

Floorplate

Neuroepithelial tissue that lines the medio-ventral part of the neural tube and that constitutes an important signalling domain in dorsal–ventral patterning of the spinal cord.

Intraflagellar transport

Bidirectional transport of particles between the cilia tip and the cell body. Important for assembly and maintenance of cilia.

Exocyst

A protein complex that tethers vesicles to the plasma membrane prior to fusion.

SNARE complexes

Transient protein complexes formed by v-SNARES on exocytic vesicles and t-SNARES in the plasma membrane that drives vesicle fusion.

Glycosphingolipids

A class of glycosylated lipids that are enriched in the outer leaflet of the plasma membrane.

Apical membrane initiation site

(AMIS). A term initially coined in mammalian epithelial cysts in 3D culture. The AMIS is a transient structure, marked by scaffolding and junctional proteins such as PAR-3, ZO-1 and cingulin, that marks the site where apical vesicles will fuse to begin forming the apical domain.

Midbody

A tubulin-rich structure present at the midpoint between dividing cells just before abscission.

Amnioserosa

An extra-embryonic tissue that covers the dorsal side of the developing Drosophila melanogaster embryo.

Snail

A zinc-finger transcription factor that acts to repress expression of genes, including cadherin-encoding genes, which is known for its role in mediating epithelial–mesenchymal transition (EMT).

Radial glial cells

Progenitor cells within the vertebrate central nervous system with long radial processes that guide radial migration of newborn neurons.

Sensory organ precursors

Progenitor cells in the Drosophila melanogaster peripheral nervous system that divide asymmetrically within the plane of the epithelium and give rise to the sensory bristles.

Germ band extension

A process that elongates the body axis of early Drosophila melanogaster embryos, whereby the epithelial tissue simultaneously converges along the dorsal–ventral axis and extends along the anterior–posterior axis.

Convergence–extension

The extension of tissue in one axis and narrowing in the orthogonal axis, driven by both cell migration and cell intercalation. Important for body axis elongation.

Microvillus inclusion disease

A rare genetic disorder causing severe diarrhoea and defects in nutrient absorption that is characterized by the loss of the apical brush border in intestinal enterocytes and the presence of intracellular inclusions containing microvilli.

TGFβ

A cytokine that has wide-ranging effects, including on cell growth, differentiation and apoptosis, and promotes epithelial–mesenchymal transition (EMT).

SMAD

A group of transcription factors serving as the main transducers of TGFβ signalling.

Ezrin

An ezrin, moesin, radixin (ERM) protein that links the plasma membrane to the cortical actin cytoskeleton.

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Buckley, C.E., St Johnston, D. Apical–basal polarity and the control of epithelial form and function. Nat Rev Mol Cell Biol 23, 559–577 (2022). https://doi.org/10.1038/s41580-022-00465-y

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