Planar Cell Polarity Pathway in Kidney Development and Function

Abstract

The evolutionarily conserved planar cell polarity (PCP) signaling pathway controls tissue polarity within the plane orthogonal to the apical-basal axis. PCP was originally discovered in Drosophila melanogaster where it is required for the establishment of a uniform pattern of cell structures and appendages. In vertebrates, including mammals, the PCP pathway has been adapted to control various morphogenetic processes that are critical for tissue and organ development. These include convergent extension (crucial for neural tube closure and cochlear duct development) and oriented cell division (needed for tubular elongation), ciliary tilting that enables directional fluid flow, and other processes. Recently, strong evidence has emerged to implicate the PCP pathway in vertebrate kidney development. In this review, we will describe the experimental data revealing the role of PCP signaling in nephrogenesis and kidney disease.

Immunocytochemical Analysis of Endogenous Frizzled-(Co-)Receptor Interactions and Rapid Wnt Pathway Activation in Mammalian Cells

“…After 5 min, the level of cellular p-MYPT1 (normalized to vehicle-treated controls) remained constant until 60 min of Wnt5A stimulation ( Figure 4 k). Since Wnt/PCP was shown to play a major role during embryonic kidney development in mammals [ 22 ], we verified these findings in the well-established human embryonic kidney cell line HEK293 as a Wnt/PCP-positive control. The results of this verification are summarized in Supplemental Figure S5 .…”

Transcriptional regulation of cell shape during organ morphogenesis

“…This budding process is driven by extensive cell movements within the duct epithelium regulated by the glial cell line–derived neurotrophic factor (GDNF) signaling through its receptor RET (receptor tyrosine kinase) and coreceptor GFAR1 ( Brophy et al, 2001 ; Takahashi, 2001 ; Tang et al, 2002 ; Arighi et al, 2005 ; Costantini and Kopan, 2010 ). GDNF is expressed in the underlying MM downstream of Eya1 and Hox11 ( Xu et al, 1999 ; Rocque and Torban, 2015 ), while RET and GFAR1 are expressed in the Wolffian duct epithelium governed by Gata3 ( Gong et al, 2007 ; Grote et al, 2008 ). GDNF expression in the MM is also maintained and reinforced by Wnt11 ( Majumdar et al, 2003 ), which is regulated by canonical Wnt/β-catenin signaling downstream of Wnt9b ( Karner et al, 2011 ).…”