Planar cell polarity (PCP) and Wnt signaling in renal disease

Abstract

Dysfunctional cilia cause kidney cysts. Most cilia are non-motile (primary) microtubular organelles expressed on epithelial cells that are thought to translate global positional cues into planar cell polarity (PCP), a pathway ascribed to non-canonical Wnt signaling. The PCP pathways then seem to ensure normal renal development by orienting the spindle axis of dividing epithelial cells along the axis of the developing kidney tubule (oriented cell division), and/or by orchestrating cell migration and intercalation, a morphogenetic program observed during vertebrate gastrulation (convergent extension). PCP signaling requires a set of proteins originally identified as PCP core proteins in Drosophila. Several observations now suggest that intact ciliogenesis and ciliary functions require the presence of PCP proteins, while the subcellular localization of core PCP proteins is not affected by ciliary defects. Furthermore, ciliary defects may be overcome by enhanced cell intercalation controlled by the PCP pathway, opening potentially exciting new avenues to prevent cyst formation.