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From cells to organs: building polarized tissue

Nature Reviews Molecular Cell Biology volume 9, pages 887–901 (2008)Cite this article

Key Points

  • Most cells in the body are polarized, showing some level of shape and functional asymmetry, such as apico–basal or front–back polarity.

  • Tissues are formed from the coordinated integration of individual cells into a multicellular structure, such as an epithelial tube.

  • Polarity is established and controlled by highly conserved core complexes, including the PAR, Crumbs and Scribble complexes.

  • Epithelial–mesenchymal transition and mesenchymal–epithelial transition are two processes by which cells can convert between two major types of cell polarity. Transcription factors that control these processes do so by controlling cell adhesion, extracellular matrix interactions and polarity complexes.

  • Polarized tissues, such as tubular epithelia, form and are regulated by various mechanisms, which enable the formation of luminal structures.

  • The extracellular matrix is a key determinant of tissue-polarity establishment, orientation and maintenance.

Abstract

How do animal cells assemble into tissues and organs? A diverse array of tissue structures and shapes can be formed by organizing groups of cells into different polarized arrangements and by coordinating their polarity in space and time. Conserved design principles underlying this diversity are emerging from studies of model organisms and tissues. We discuss how conserved polarity complexes, signalling networks, transcription factors, membrane-trafficking pathways, mechanisms for forming lumens in tubes and other hollow structures, and transitions between different types of polarity, such as between epithelial and mesenchymal cells, are used in similar and iterative manners to build all tissues.

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Figure 1: Cell polarization in diverse tissue types.
Figure 2: EMT and MET in tissue morphogenesis.
Figure 3: Cavitation, hollowing and membrane repulsion as lumen-forming mechanisms.
Figure 4: Membrane traffic and apical extracellular matrix secretion during lumen formation and expansion.

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Acknowledgements

This work was supported by National Institutes of Health grants to K.E.M. and a Susan G. Komen Foundation Postdoctoral Fellowship to D.M.B. We thank R. Metzger, C. A. Hunt and A. J. Ewald for comments on the manuscript and members of our laboratory for discussions. This paper is dedicated to the memory of our colleagues S. Ross and P. Kolodzeij.

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Authors and Affiliations

  1. Department of Anatomy, University of California San Francisco, California, 94143-2140, USA

    David M. Bryant & Keith E. Mostov

  2. Departments of Biochemistry and Biophysics, University of California San Francisco, California, 94143-2140, USA

    Keith E. Mostov

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Glossary

Basement membrane

A thin extracellular matrix layer that specifically lines the basal side of epithelial sheets, and certain other tissues, to which cells are attached. Also referred to as the basal lamina.

Extracellular matrix

An extracellular scaffolding gel that consists of fibrous structural proteins, complex sugars, fluid and signalling molecules.

Tight junction

A diffusion barrier-forming junction at the apical-most region of the lateral membrane of vertebrate epithelial cells.

Design principle

A simple rule that increases the likelihood of the proper assembly and function of a system.

Mesenchymal–epithelial transition

The de novo acquisition of epithelial characteristics, such as apico–basal polarity and epithelial-type junctions, by mesenchymal cells.

Epithelial–mesenchymal transition

The transition of epithelial cells to a mesenchymal state by complete loss of apico–basal polarity, epithelial-type junctions, basement membrane and the adoption of migratory behaviours.

Front–back polarity

A morphological characteristic, particularly in migratory cells, wherein the front (leading edge) and the back (uropod) show morphological and functional asymmetry.

Polarity complexes

Conserved, multimeric protein complexes that promote and modulate the formation of asymmetric cellular architecture in diverse tissue types and organisms.

Planar cell polarity

(PCP). The polarization of epithelial cells along the plane of the epithelium, orthogonal to the apico–basal axis, directing the orientation of cell shape, division, movement and differentiation. Non-epithelial cells can also exhibit PCP.

Zero-order ultrasensitivity

A reversible system, such as phosphorylation, where modifying enzymes can become saturated with regard to the protein being modified, resulting in a switch-like movement of the substrate between modification states.

Condensation

An event wherein non-adherent or loosely adherent cells can move together and tightly adhere to one another.

Partial EMT

The transient adoption of some mesenchymal characteristics by epithelial cells without complete or permanent loss of the epithelial phenotype.

Exocyst

A highly conserved, octameric protein complex that regulates vesicle docking and delivery to the cell surface.

Hepatocyte growth factor

(HGF). A multipotent ligand, also known as scatter factor, for the c-Met receptor. HGF induces proliferation, scattering motility and branching morphogenesis in many epithelia.

Transforming growth factor-β

Cytokine ligand that induces strong epithelial–mesenchymal transition in many epithelial cells and tissues.

MDCK

Madin–Darby canine kidney cells. A polarized epithelial cell line that is commonly used for studies of polarity, membrane trafficking and cell adhesion.

Guanine nucleotide-exchange factor

A protein that catalyses the exchange of GDP for GTP on GTPase proteins, thereby 'activating' the GTPase.

GTPase-activating protein

Protein that catalyses hydrolysis of GTP to GDP on GTPase proteins, thereby 'inactivating' the GTPase.

Evagination

The deformation of an epithelial sheet, without the loss of apico–basal polarity, such that part of the sheet extrudes into the extracellular matrix.

Invagination

The deformation of an epithelial sheet, without the loss of apico–basal polarity, such that part of the sheet folds into the lumen of the tube.

Radial tissue symmetry

The complimentary arrangement of cell polarity in a symmetric manner around a central line, such as the apical surfaces of cells in a biological tube.

Cavitation

The formation of a lumen between a group of cells by apoptosis of inner cells that are not in contact with the extracellular matrix.

Hollowing

The trafficking of vesicles containing apical membrane to a space between cells, or in a single cell, to form a lumen de novo.

Membrane repulsion

Activation of a signalling cascade that promotes membranes between cells to de-adhere or that inhibits any attraction between membrane regions.

Mammary end bud

The spherical end of a mammary tubule; referred to as an acinus when fully enclosed in 3D culture.

COPI and COPII

Coatomer protein complexes that regulate anterograde (COPII) and retrograde (COPI) membrane transport between the endoplasmic reticulum and through cisternae of the Golgi complex.

Autocellular junctions

The formation of junctional complexes in a single cell. They can be used to form a lumen in a single cell.

Chain

The extension of one or more cells that have lost apico–basal polarity from an epithelial sheet into the extracellular matrix without losing cell–cell adhesion or becoming multilayered.

Cord

Similar to the formation of a chain, but comprised of multilayering of cells that may contain some disconnected luminal structures. Can build on successful chain extension.

Polycystic kidney disease

A group of diseases that cause focal dilation of kidney tubules resulting in the formation of large cysts and severely compromised renal function.

Vascular stenosis

A pathological vascular condition that involves the narrowing of blood vessels and that results in hypoperfusion of tissues.

Septate junction

(SJ). An invertebrate cell–cell junction, localized to the mid-lateral membrane region. Like vertebrate tight junctions (TJs), SJs provide a paracellular diffusion barrier. Unlike TJs, SJs contain basolateral, rather than apical, polarity determinants.

Chitin

A polysaccharide that consists of N-acetylglucosamine, the polymer of which is a primary component of insect cytoskeletons.

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Bryant, D., Mostov, K. From cells to organs: building polarized tissue. Nat Rev Mol Cell Biol 9, 887–901 (2008). https://doi.org/10.1038/nrm2523

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