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Planar cell polarity pathway in kidney development, function and disease

Nature Reviews Nephrology volume 17, pages 369–385 (2021)Cite this article

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Abstract

Planar cell polarity (PCP) refers to the coordinated orientation of cells in the tissue plane. Originally discovered and studied in Drosophila melanogaster, PCP is now widely recognized in vertebrates, where it is implicated in organogenesis. Specific sets of PCP genes have been identified. The proteins encoded by these genes become asymmetrically distributed to opposite sides of cells within a tissue plane and guide many processes that include changes in cell shape and polarity, collective cell movements or the uniform distribution of cell appendages. A unifying characteristic of these processes is that they often involve rearrangement of actomyosin. Mutations in PCP genes can cause malformations in organs of many animals, including humans. In the past decade, strong evidence has accumulated for a role of the PCP pathway in kidney development including outgrowth and branching morphogenesis of ureteric bud and podocyte development. Defective PCP signalling has been implicated in the pathogenesis of developmental kidney disorders of the congenital anomalies of the kidney and urinary tract spectrum. Understanding the origins, molecular constituents and cellular targets of PCP provides insights into the involvement of PCP molecules in normal kidney development and how dysfunction of PCP components may lead to kidney disease.

Key points

  • Planar cell polarity (PCP) refers to the coordinated organization of cells or cell components across a tissue plane as exemplified by the uniform patterns of scales on fish, trichomes (small hairs) on Drosophila wings or stereocilia in the mammalian inner ear.

  • Evolutionarily conserved PCP proteins function in specialized signalling pathways to coordinate changes in cell shape and behaviour through processes that commonly involve actomyosin activation; these PCP-dependent changes in cell morphology control tissue morphogenesis.

  • PCP proteins exhibit asymmetric subcellular localization along the tissue plane.

  • Functions of vertebrate homologues of Drosophila PCP components in PCP signalling are often unclear owing to gene redundancy and/or their involvement in non-PCP-related processes.

  • Given the essential roles of PCP proteins in morphogenetic processes, mutations in genes that encode PCP components can cause congenital malformations in multiple organs and tissues, including the kidney. Defective PCP signalling influences ureteric bud outgrowth and branching, nephron progenitor cell renewal and differentiation, and podocyte development. In mouse PCP mutants, renal tubules are dilated but no cysts form.

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Fig. 1: Planar cell polarity in Drosophila wing.
Fig. 2: Cell behaviours during morphogenesis.
Fig. 3: PCP signalling in kidney development.
Fig. 4: The relationship between PCP and cystogenesis.
Fig. 5: Cues for establishing PCP during kidney development.

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Acknowledgements

The authors thank L. Gusella (Icahn School of Medicine at Mount Sinai, New York, NY, USA) for comments on the manuscript before submission. We apologize to those investigators whose studies we could not cite due to the constraints for space. The authors’ work was supported by grants from the Kidney Foundation of Canada KFOC1719 and the Canadian Institute of Health Research (MOP130315 and PJT-169082) to E.T. and National Institutes of Health grants (GM122492, HD092990, DE027665 and NS100759) to S.Y.S.

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Authors and Affiliations

  1. McGill University, Montreal, Quebec, Canada

    Elena Torban

  2. McGill University Health Center Research Institute, Montreal, Quebec, Canada

    Elena Torban

  3. Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Sergei Y. Sokol

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  1. Elena Torban
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The authors contributed equally to all aspects of the article.

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Correspondence to Elena Torban or Sergei Y. Sokol.

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Nature Reviews Nephrology thanks R. Miller, M. Simons and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Genitourinary Development Molecular Anatomy Project (GUDMAP): www.gudmap.org

Supplementary information

Glossary

Insect cuticle

An extracellular layer that covers the external surface of the epidermis in many insects.

Functional drift

Acquisition of a diverse function or functions by homologous genes.

Germband extension

A morphogenetic process similar to vertebrate convergent extension, in which the segmented trunk of an insect embryo (germband) elongates along the anteroposterior axis and narrows along the dorsoventral axis.

Non-centrosomal microtubules

Microtubular arrays that do not originate from the centrosome. In many polarized epithelia non-centrosomal microtubules are aligned along the apical–basal axis with their minus ends oriented towards the apical surface.

SNARE proteins

A diverse group of proteins that enable docking and fusion of cargo vesicles with the target membrane such as plasma or ciliary membrane.

Neural folds

Elevated structures in the flanking areas of the neural plate that bend towards each other and fuse to form the neural tube.

Mouse node

Cell population at the distal tip (anterior primitive streak) of the gastrulating mouse embryo that secretes signalling factors regulating cell movements and the body axes.

Gastrocoel roof plate

A transient patch of ciliated endodermal cells in frog embryos that controls left–right patterning.

Kupffer vesicle

A transient ciliated organ at the posterior end of the zebrafish embryo that is required for left–right patterning, similar to the frog gastrocoel roof plate and mouse posterior node.

Centrosome

A microtubule-based organelle that consists of two centrioles and functions to regulate cell divisions and ciliary growth.

Paralogs

Homologous genes that originate in the same species as a result of gene duplication.

Multicellular rosette

A group of five or more cells exhibiting coordinated behaviours, including the formation of a transient single contact (vertex), that result in tissue convergence and extension.

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Torban, E., Sokol, S.Y. Planar cell polarity pathway in kidney development, function and disease. Nat Rev Nephrol 17, 369–385 (2021). https://doi.org/10.1038/s41581-021-00395-6

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