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Planar cell polarity in development and disease

Nature Reviews Molecular Cell Biology volume 18, pages 375–388 (2017)Cite this article

Subjects

Key Points

  • Planar cell polarity (PCP) is a polarity axis that organizes cells in the plane of the tissue. PCP is conserved in metazoans and is essential for proper development and tissue homeostasis.

  • Asymmetric and mutually exclusive subcellular enrichment of key PCP proteins patterns cells in planar-polarized tissues. PCP proteins also coordinate planar polarity between cells and control polarized behaviours by modulating the cytoskeleton.

  • PCP patterns develop gradually from an initially disordered state through dynamic trafficking and various feedback interactions that can influence protein localization and stability.

  • PCP patterns seem to be globally oriented along a pre-defined axis in a given tissue. Notably, multiple mechanistic inputs may have differential influences on PCP patterning depending on developmental timing and tissue context, and may only partially overlap in different contexts.

  • The morphogenetic events governed by PCP signalling are best understood in Drosophila melanogaster, in which the particular orientation of hairs and bristles on the fly body has served to unravel basic principles of PCP-dependent processes. Information obtained from this model has helped to better understand equivalent mechanisms in vertebrates, particularly in the context of the orientation of fluid flow mediated by multiciliated cells and cell rearrangements during convergent extension.

  • Mutations in PCP genes have been implicated in diverse human pathologies, and the body of evidence supporting the involvement of PCP aberrations in human birth defects continues to grow rapidly.

Abstract

Planar cell polarity (PCP) is an essential feature of animal tissues, whereby distinct polarity is established within the plane of a cell sheet. Tissue-wide establishment of PCP is driven by multiple global cues, including gradients of gene expression, gradients of secreted WNT ligands and anisotropic tissue strain. These cues guide the dynamic, subcellular enrichment of PCP proteins, which can self-assemble into mutually exclusive complexes at opposite sides of a cell. Endocytosis, endosomal trafficking and degradation dynamics of PCP components further regulate planar tissue patterning. This polarization propagates throughout the whole tissue, providing a polarity axis that governs collective morphogenetic events such as the orientation of subcellular structures and cell rearrangements. Reflecting the necessity of polarized cellular behaviours for proper development and function of diverse organs, defects in PCP have been implicated in human pathologies, most notably in severe birth defects.

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Figure 1: Asymmetric signalling complexes pattern planar polarity.
Figure 2: Graphical summary of endocytosis, trafficking and degradation events that facilitate the dynamic patterning of planar cell polarity.
Figure 3: Multiple global inputs can collectively influence planar cell polarity orientation and stability across developing tissues.
Figure 4: Planar cell polarity patterns direct the cytoskeletal organization and ciliary polarity of multiciliated cells.
Figure 5: Planar cell polarity signalling directs polarized cell rearrangements during convergent extension.

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Acknowledgements

J.B.W. is supported by grants from the National Heart, Lung, and Blood Institute (R01HL117164), the National Institute of General Medical Sciences (R01 GM104853-02) and the National Institute of Child Health and Human Development (1R01HD085901, 5R21HD084072).

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Authors and Affiliations

  1. Department of Molecular Biosciences, Patterson Labs, 2401 Speedway, The University of Texas at Austin, Austin, 78712, Texas, USA

    Mitchell T. Butler & John B. Wallingford

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  1. Mitchell T. Butler
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Correspondence to John B. Wallingford.

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Supplementary information

Supplementary information S1 (box)

Apico-basal versus Planar Cell Polarity (PDF 496 kb)

Supplementary information S2 (box)

Planar cell polarity and the actin cytoskeleton (PDF 99 kb)

PowerPoint slides

Glossary

Notum

The dorsal region of the thorax of a mature insect.

Trichome

An actin-based hair found on each cell of the fly wing blade that emanates from the apical, distal side of the cells and points distally — properties that are controlled by planar cell polarity signalling.

Endocytic flux

The constant endocytosis and subsequent recycling of unstable protein components associated with the plasma membrane.

Rab GTPase family

A large family of small GTPases central to membrane trafficking regulation.

Dynamin

A GTPase protein critical for driving membrane fission that facilitates endocytic events.

Clathrin

A vesicular coating component that has an important structural role in mediating endocytosis of membrane-associated proteins.

Polo-like kinase 1

(PLK1). A Ser/Thr kinase that serves as an important cell cycle regulator, playing a notable part during the G2–M transition.

Protocadherins

The largest subgroup of cadherins with variable extracellular domains and diverse cytoplasmic domains that distinguish their variety of potential functions from those of classical cadherins.

Mutant clones

Groups of cells in a tissue that have perturbed gene expression and are surrounded by or interspersed between otherwise wild-type cells.

Ommatidia

Optical units of insect compound eyes containing groups of polarized photoreceptive cells.

Central fold

Midline of the neural plate that divides the left and right half; it comprises cells that apically constrict to facilitate neural plate folding and neural tube closure.

Neural plate

A sheet of neuroepithelial cells that undergo convergent extension, apical constriction and regional folding to form the vertebrate neural tube.

Kinocilium

A microtubule-based protrusion on the apical surface of hair cells in tissues of the inner ear that guides the polarized orientation of an actin-based stereociliary bundle.

Basal bodies

Modified centrioles and accessory proteins that serve as specialized microtubule-organizing centres at the base of the cilium, which they nucleate.

Ependymal cells

Multiciliated cells that line the interface between the central nervous system and cerebrospinal fluid, which propel cerebrospinal flow through the brain ventricles and central spinal canal.

Non-canonical tubulins

Tubulin superfamily members that are not conserved in all eukaryotes as α-, β-, and γ-tubulin are; non-canonical tubulins often function as centriole accessory structures.

Traction force

The forces exerted across the junction between two cells that facilitate cell rearrangements and tissue morphogenesis.

Septins

Cytoskeletal components that upon binding to GTP can polymerize into ordered structures such as rings and filaments, which can function as scaffolds or diffusion barriers, for example.

Spina bifida

A neural tube defect associated with a regional, incomplete closure of the spinal cord and associated tissues.

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Butler, M., Wallingford, J. Planar cell polarity in development and disease. Nat Rev Mol Cell Biol 18, 375–388 (2017). https://doi.org/10.1038/nrm.2017.11

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