Polarity in physics is defined as 'that quality or condition of a body in virtue of which it exhibits opposite or contrasted properties or powers, in opposite or contrasted parts or directions' [1]. Examples of polarized physical systems include magnets and batteries. In biology, polarity refers to the asymmetric distribution of subcellular components, resulting in an asymmetric cell morphology, behavior or function. In other words, in a polarized cell one region looks or acts differently from other regions of the cell. Prominent examples of polarized cell types are neurons and epithelial cells.

A common set of planar polarity genes has been shown to direct planar polarity in different contexts. These genes and their encoded proteins fall into two classes based on their genetic and molecular properties: the Frizzled system and the Fat system. The Frizzled system consists of the cell-surface proteins Frizzled, Flamingo and Van Gogh and the associated cytosolic factors Dishevelled, Diego and Prickle [2-6]. These components, also known as the core PCP proteins, promote cell polarity in part by adopting an asymmetric localization [2-6]. In the Drosophila wing epithelium, which produces a planar polarized pattern of distally directed hairs, the core PCP proteins localize to proximal or distal cell boundaries (Figure ​(Figure1b).1b). An asymmetric distribution of proteins related to Frizzled, Flamingo, Van Gogh, Dishevelled, and Prickle is also observed in some vertebrate tissues that display planar polarity [7,8]. The Fat system of planar polarity consists of the atypical cadherins Fat and Dachsous and the Golgi kinase Four-jointed [9,10]. No asymmetric distribution of these proteins has been reported.

Planar polarity is not only a complex biological process that integrates basic cell biology, cell-cell communication and dynamic changes in cell and protein interactions over time, but it is also directly relevant to human disease. Of note, some of the defects in mice mutant for planar polarity pathways appear to resemble specific human pathologies. Disrupting the Frizzled or Fat systems causes defects in closure of the mouse neural tube [7]. Neural tube defects are common congenital birth defects in humans, and mutations in VANGL1, a human homolog of Van Gogh, have been identified in patients with familial and sporadic neural tube defects [22]. Mice mutant for Diego- and Fat-related proteins have abnormal kidney development, resulting in a phenotype that resembles human polycystic kidney disease [23]. Mutations in homologs of Fat, Frizzled, Dishevelled, Flamingo and Van Gogh cause abnormal cochlear development in mice [8]. It will be of interest to determine whether abnormal planar polarity signaling is associated with similar conditions in humans.

Quantifying the polarized distribution of a protein (or any other biological phenomenon) makes it possible to compare different samples and genotypes using statistical methods. Fluorescence ratios can reveal significant differences in the degree of polarity in different contexts, and thus have advantages over a qualitative plus/minus assessment. The use of fluorescence ratios also has the advantage of detecting planar polarity earlier than is apparent from assaying the cellular outcome of asymmetric protein activity. For example, core PCP proteins are asymmetrically localized in the Drosophila wing several hours before wing hair formation, and polarized movement of vesicles containing Frizzled can be detected even earlier by combining quantitative fluorescence measurements with live-cell imaging [24]. In the Drosophila embryo, cytoskeletal and junctional proteins localize to complementary planar domains within cells before the onset of polarized cell movements during axis elongation. Quantitative analysis revealed that the actin cytoskeleton is the first known structure to become planar polarized in this process [25]. A timeline of the onset of different molecular asymmetries can elucidate the symmetry-breaking events and signaling cascades that establish planar polarity.