Dissecting the PCP pathway: One or more pathways?

Abstract

Planar cell polarity (PCP), the alignment of cells within 2D tissue planes, involves a set of core molecular regulators highly conserved between animals and cell types. These include the transmembrane proteins Frizzled (Fz) and VanGogh and the cytoplasmic regulators Dishevelled (Dsh) and Prickle. It is widely accepted that this core forms part of a 'PCP pathway' for signal transduction, which can affect cell morphology through activation of an evolutionary ancient regulatory module involving Rho family GTPases and Myosin II, and/or the JNK kinase cascade. We have re-examined the evidence for interactions between the proposed PCP pathway components, and question the placing of the cell morphology regulators in the same pathway as the PCP core. While Fz and Dsh are clearly involved in both PCP and Rho-based cell morphology regulation, available evidence cannot currently discriminate whether these processes are linked mechanistically by a shared Fz/Dsh population, or pass by two distinct pathways.

Evidence for Involvement of Wnt Signalling in Body Polarities, Cell Proliferation, and the Neuro-Sensory System in an Adult Ctenophore

“…Alternative (“non-canonical”) Wnt signalling pathways use downstream cascades independent from β-catenin, the Axin/GSK-3β/APC complex and TCF, but yet often involve Fz receptors and their cytoplasmic partner Dvl like in the canonical pathway. One of these “non-canonical” Wnt pathways, termed Wnt/PCP (for planar cell polarity), is thought to work either through Rho family GTPases or JNK regulatory modules, but might in fact represent two distinct pathways (Fz-PCP and Fz-Rho, [11]). In another β-catenin independent pathway (Wnt/Ca 2+ ), Wnts can bind to non-Fz receptors (Ryk) and intracellular effects are triggered by an increase of Ca 2+ release to the cytoplasm caused by activation of phospholipase-C (PLC) [10].…”

“…Among these genes, Wnt ligands, Fz receptors, and Dvl proteins are upstream components shared by several signalling pathways. Fz and Dvl proteins are also thought to function in the so-called Fz-PCP pathway independently from both Wnt ligands and the downstream canonical machinery [11]. Likewise the β-catenin protein has multiple cellular functions besides its role in Wnt canonical signalling, notably in cell adhesion complexes [47], and GSK-3β is a highly pleiotropic cytoplasmic enzyme [48], [49].…”

Differential Responses to Wnt and PCP Disruption Predict Expression and Developmental Function of Conserved and Novel Genes in a Cnidarian

“…One aspect of this is that transient up-regulation of some oral genes and down-regulation for some aboral genes due to PCP disruption, as shown in Stbm-MO embryos[41], could in Fz-MO embryos counterbalance and dampen the effects of Wnt/β-catenin signaling. Concerning the non-axial genes the strong effects of PCP disruption could reflect direct signaling through ‘non-canonical’ intracellular pathways acting downstream of Fz/Dsh [64]. Given the transient nature of the effect, however, we favor the possibility that the effect is indirect, resulting from the developmental programs of the corresponding cell lineages being delayed or accelerated by a changed morphological environment.…”

Cell polarity: having and making sense of direction—on the evolutionary significance of the primary cilium/centrosome organ in Metazoa

“…Their appearance during the evolution of multicellularity in the animal lineage suggests a role in coordinating more ancient cell polarity characters within tissues. Wnt appeared with animal multicellularity, whereas components involved in cell shape and motility were present in ancestral unicellular organisms [295]. Many links have been shown between cellular processes like ciliogenesis, apical docking of basal bodies or cell intercalation during gastrulation and the Wnt/Fz signalling.…”

“…As a whole, PCP development along the principal body axis in the early embryo might have had important consequences for body plan evolution by allowing coordination along the body axis of cell behaviours during morphogenetic processes, such as gastrulation and elongation of the embryo [295]. …”