Planar cell polarity signaling: the developing cell's compass

Abstract

Cells of many tissues acquire cellular asymmetry to execute their physiologic functions. The planar cell polarity system, first characterized in Drosophila, is important for many of these events. Studies in Drosophila suggest that an upstream system breaks cellular symmetry by converting tissue gradients to subcellular asymmetry, whereas a downstream system amplifies subcellular asymmetry and communicates polarity between cells. In this review, we discuss apparent similarities and differences in the mechanism that controls PCP as it has been adapted to a broad variety of morphological cellular asymmetries in various organisms.

Figure 1.

Planar cell polarity in Drosophila. (A) Image of wild type (top panel) and PCP mutant Drosophila pupal wing epithelium, labeled with phalloidin to stain actin. (B) Schematic of PCP protein asymmetric cortical distribution in the fly wing epithelium showing Pk and Vang enriched on the proximal, Fz, Dsh, and Dgo on the distal and Fmi on both proximal and distal sides of each cell. (C) A model for organization of the PCP pathway in Drosophila. Heterodimers of Ft and Ds show biased orientation at each cell boundary, resulting from graded expression of Fj and Ds. Asymmetrically oriented Ft-Ds heterodimers bias the function of a feedback loop consisting of the core PCP proteins, Fmi, Fz, Dsh, Dgo, Vang, and Pk.

Figure 2.

Core PCP protein distribution in planar polarized tissues in Drosophila and vertebrates. Asymmetric cortical distribution of core PCP components is a highly conserved feature of the PCP pathway. Pk/Vang and Fz/Dsh/Dgo complexes segregate to opposite cortical domains in the fly wing, eye, SOP cell, and vertebrate sensory hair cell. The relative cortical distribution of PCP complexes remains untested in individual mammalian hair follicle precursor cells. Asymmetric cortical PCP complexes have not been reported in vertebrate multiciliated epithelial cells; instead, Dsh and Vang localize to the basal bodies.

Figure 3.

PCP components regulate contact inhibition of locomotion in migrating neural crest cells. Schematic of neural crest cell migration showing cells breaking away from the epithelial sheet leading edge, migrating toward each other, and forming an interface, which then collapses and prompts cells to migrate in opposite directions. Initially, PCP components have uniform distributions, but then relocalize to the site of cell–cell contact. PCP components are required to arrest and then alter the migration path, possibly through activation of RhoA.