The Biological Significance and Implications of Planar Cell Polarity for Nephrology.

Eugenia Papakrivopoulou,Charlotte H. Dean,Daniyal J. Jafree,David A. Long

doi:10.3389/fphys.2021.599529

Abstract

The orientation of cells in two-dimensional and three-dimensional space underpins how the kidney develops and responds to disease. The process by which cells orientate themselves within the plane of a tissue is termed planar cell polarity. In this Review, we discuss how planar cell polarity and the proteins that underpin it govern kidney organogenesis and pathology. The importance of planar cell polarity and its constituent proteins in multiple facets of kidney development is emphasised, including ureteric bud branching, tubular morphogenesis and nephron maturation. An overview is given of the relevance of planar cell polarity and its proteins for inherited human renal diseases, including congenital malformations with unknown aetiology and polycystic kidney disease. Finally, recent work is described outlining the influence of planar cell polarity proteins on glomerular diseases and highlight how this fundamental pathway could yield a new treatment paradigm for nephrology.

Highlights

The generation of normal adult renal structure and function is defined by the diversity of cell types within the kidney, and the orientation of these cells in two-dimensional and threedimensional space
Celsr1 and Vangl2 interact during the branching of the ureteric bud, as may be the case for FZD4 and FZD8 (Ye et al, 2011). These findings suggest that planar cell polarity (PCP) proteins regulate branching morphogenesis in the kidney, the implication of planar-polarised behaviour in this process requires the identification of molecular asymmetry of PCP proteins in ureteric bud epithelium
Whether glomerular defects in these mouse models arise from planar-polarised behaviours is not clear, as the asymmetry of expression of VANGL2 other PCP proteins has not been shown in podocytes or other glomerular cell types

Summary

Introduction

The generation of normal adult renal structure and function is defined by the diversity of cell types within the kidney, and the orientation of these cells in two-dimensional and threedimensional space. Recent evidence indicates the asymmetric localisation of VANGL and FZD proteins on opposing cell-cell boundaries of collecting duct and proximal tubule cells; an asymmetry that is lost in Vangl2Lp/Lp and Fzd3−/−; Fzd6−/− kidneys (Kunimoto et al, 2017), indicative of planar-polarised behaviour during tubule formation.

Results

Conclusion