Centriole positioning in epithelial cells and its intimate relationship with planar cell polarity

Abstract

Planar cell polarity (PCP)-signaling and associated tissue polarization are evolutionarily conserved. A well documented feature of PCP-signaling in vertebrates is its link to centriole/cilia positioning, although the relationship of PCP and ciliogenesis is still debated. A recent report in Drosophila established that Frizzled (Fz)-PCP core signaling has an instructive input to polarized centriole positioning in non-ciliated Drosophila wing epithelia as a PCP read-out. Here, we review the impact of this observation in the context of recent descriptions of the relationship(s) of core Fz-PCP signaling and cilia/centriole positioning in epithelial and non-epithelial cells. All existing data are consistent with a model where Fz-PCP signaling functions upstream of centriole/cilia positioning, independent of ciliogenesis. The combined data sets indicate that the Fz-Dsh PCP complex is instructive for centriole/ciliary positioning via an actin-based mechanism. Thereby, centriole/cilia/centrosome positioning can be considered an evolutionarily conserved readout and common downstream effect of PCP-signaling from flies to mammals.

Wnt/PCP Instructions for Cilia in Left-Right Asymmetry

“…In addition, previous work in zebrafish also suggested a link between core Fz/PCP factors and basal body/cilia positioning along the anteroposterior axis in the cells of the neural tube (Borovina et al, 2010), where the basal body/cilium localized to the posterior side of each cell, away from the Vang-Pk complexes, like in Drosophila and the current mouse study. Taken together with Minegishi et al (2017), these observations indicate that ciliary/basal body positioning, and similarly centriole localization in Drosophila , is a key evolutionarily conserved readout of Wnt-Fz/PCP signaling, as was recently proposed (Carvajal-Gonzalez et al, 2016b). …”

Insights into the Etiology of Mammalian Neural Tube Closure Defects from Developmental, Genetic and Evolutionary Studies

“…A prerequisite is the directional orientation of cells relative to a morphogenic signal. The cells become asymmetrical in the positioning of various subcellular structures, including the core proteins of the PCP pathway [ 14 , 15 ]. Mutations in PCP genes interfere with the directionality of neuroepithelial cell movement in a variety of gene-specific ways [ 16 ].…”

“…Mutations in PCP genes interfere with the directionality of neuroepithelial cell movement in a variety of gene-specific ways [ 16 ]. The planar cell polarity (PCP) pathway is complex, comprising two main sets of interacting genes, the “core” pathway, and the Fat-Dachsous pathway, probably connected by Prickle [ 14 ]. The “core” pathway is highly conserved and is regulated by gradients of particular Wnt proteins, (e.g., Wnt5a and Wnt11 ).…”

“…The “core” pathway is highly conserved and is regulated by gradients of particular Wnt proteins, (e.g., Wnt5a and Wnt11 ). The “core” proteins include the transmembrane receptors Vangl1/2 , Celsr1/2/3 , and Fzd (Frizzled) and the cytosolic proteins Dvl , Prickle , Inversin ( Invs ) and Scrib [ 14 ]. The Fat/Dachsous pathway, acting upstream or in parallel with the PCP core pathway, includes the large membrane cadherins, Fat and Dchs , which bind to each other and are regulated by Fjx [ 5 ].…”

“…In addition to its essential role in planar cell polarity required for convergent extension, the PCP pathway affects ciliogenesis, the arrangement of cytoskeletal actin and microtubules, the basal body and the centriole within cells [ 14 , 17 , 18 ]. Small Rho family-GTPases regulate the localization of actin polymerization.…”