Wnt-frizzled planar cell polarity signaling in the regulation of cell motility

Abstract

The molecular complexes underlying planar cell polarity (PCP) were first identified in Drosophila through analysis of mutant phenotypes in the adult cuticle and the orientation of associated polarized protrusions such as wing hairs and sensory bristles. The same molecules are conserved in vertebrates and are required for the localization of polarized protrusions such as primary or sensory cilia and the orientation of hair follicles. Not only is PCP signaling required to align cellular structures across a tissue, it is also required to coordinate movement during embryonic development and adult homeostasis. PCP signaling allows cells to interpret positional cues within a tissue to move in the appropriate direction and to coordinate this movement with their neighbors. In this review we outline the molecular basis of the core Wnt-Frizzled/PCP pathway, and describe how this signaling orchestrates collective motility in Drosophila and vertebrates. Here we cover the paradigms of ommatidial rotation and border cell migration in Drosophila, and convergent extension in vertebrates. The downstream cell biological processes that underlie polarized motility include cytoskeletal reorganization, and adherens junctional and extracellular matrix remodeling. We discuss the contributions of these processes in the respective cell motility contexts. Finally, we address examples of individual cell motility guided by PCP factors during nervous system development and in cancer disease contexts.

Keywords: Cancer cell migration; Cell adhesion; Cell motility; Cell polarity; Cytoskeletal remodeling; Gastrulation; Neuronal development; Planar cell polarity; Wnt-frizzled signaling.