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 inDrosophila melanogasterwhere 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.
Highlights
We showed that Vangl2 protein is expressed at high levels in the nephric duct and in metanephric epithelium derived from both mesenchymal and ureteric bud (UB) lineages during the embryonic period [119]
These genes encode a network of signaling molecules that reorganize the cytoskeleton to enable uniform localization of cellular structures. It is well-established that mammals express homologues of fruit fly planar cell polarity (PCP) genes and that PCP gene mutations disrupt key mammalian developmental processes such as neural tube closure and hair cell arrangement in the cochlea
It is apparent that complex organs, such as the kidney, are organized along epithelial planes: cells of renal tubule are arranged so that dividing cells organize mitotic spindle alignment in the tubular plane to support linear tubular elongation; apical primary cilia are positioned and tilted uniformly to enable directional flow along the tubule to provide positional information; interdigitating podocyte foot processes are elegantly arranged along vascular flow through the capillaries which they envelop
Summary
Development of the mammalian kidney is a complex process involving repeated local interactions between progenitor cells of the intermediate mesoderm and branches of the ureteric bud that culminate in the formation of thousands (mouse) or hundreds of thousands (humans) of nephrons (extensively reviewed in [1, 2]). Nephrogenesis relies on a differentiation cascade that requires timely changes in cell shape, movement, and alignment that lead to clusters of specialized epithelia lining each segment Disturbance of these molecular and cellular events manifests in a wide variety of congenital anomalies of kidney and urinary tract in humans [3]. Mutations of PCP pathway components lead to multiple developmental abnormalities including neural tube and cardiac defects and misorientation of hair cells in the cochlea, lung, limb, facial anomalies, and other defects (reviewed in [10]). These congenital abnormalities underscore the critical role for the PCP pathway in organogenesis. We discuss how disturbances of the PCP pathway contribute to human kidney disease
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