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Journal Article
Planar cell polarity in development and disease
2017
Overview
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.
Planar cell polarity — the asymmetric distribution of proteins in the plane of a cell sheet — dictates the orientation of various subcellular structures and drives collective cell rearrangements. Better understanding of this conserved axis of polarity can shed light on the mechanisms of morphogenetic processes and explain the underlying causes of human birth defects.
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
