Asymmetric protein localization in planar cell polarity: mechanisms, puzzles, and challenges

The polarization of epithelial cells along an axis orthogonal to their apical-basal axis is increasingly recognized for roles in a variety of developmental events and physiological functions. While now studied in many model organisms, mechanistic understanding is rooted in intensive investigations of planar cell polarity (PCP) in Drosophila. Consensus has emerged that two molecular modules, referred to here as the global and core modules, operate upstream of effector proteins to produce morphological PCP. Proteins of the core module develop subcellular asymmetry, accumulating in two groups on opposite sides of cells, consistent with proposed functions in producing cell polarity and in communicating that polarity between neighboring cells. Less clear are the molecular and cell biological mechanisms underlying core module function in the generation and communication of subcellular asymmetry and the relationship between the global and the core modules. In this review, we discuss these two unresolved questions, highlighting important studies and potentially enlightening avenues for further investigation. It is likely that results from Drosophila will continue to inform our views of the growing list of examples of PCP in vertebrate systems.