Cell movements are essential in the embryo to shape the axial body plan and in the adult for homeostasis and wound healing. During vertebrate gastrulation, convergence and extension (C&E)

INTRODUCTION Cell movements are essential in the embryo to shape the axial body plan and in the adult for homeostasis and wound healing. During vertebrate gastrulation, convergence and extension (C&E) movements narrow and elongate the germ layers to form the anteroposteriorly (AP) elongated body axis that is common to vertebrate embryos (Keller, 2002; Solnica-Krezel, 2005). This morphogenetic process involves multiple cell behaviors that change according to stage and location (Roszko et al., 2009). Non-canonical Wnt/planar cell polarity (Wnt/PCP) signaling regulates C&E in chordates from ascidians through mammals by polarizing the morphology and behavior of cells (Jiang et al., 2005; Solnica-Krezel, 2005). Wnt/PCP signaling organizes sheets of cells to exhibit a consistent polarity perpendicular to the axis of the apical-basal polarity (Axelrod and McNeill, 2002; Eaton, 2003; Fanto and McNeill, 2004). In Drosophila, where planar cell polarity was discovered, PCP signaling is required to coordinate the orientation of epithelial structures in the cuticle, wing, and eye (Gubb and Garcia-Bellido, 1982; Adler, 2002). Downstream of an asymmetry cue (Strutt and Strutt, 2009), transmembrane proteins Frizzled (Fz) and Vangogh (Vang) are required in adjacent cells to initiate planar polarization. Other components of the Wnt/PCP pathway, Dishevelled (Dvl) and Prickle (Pk), amplify the difference leading to visible asymmetry in protein distribution; Fz and Dvl are found at the distal side of the cell where a hair forms, while antagonistic factors Vang and Pk are enriched at the opposite cell membrane (Usui et al., 1999; Axelrod, 2001; Feiguin et al., 2001; Shimada et al., 2001; Strutt, 2001; Tree et al., 2002; Bastock et al., 2003; Narayan et al., 2004; Simons and Mlodzik, 2008). Wnt/PCP signaling most commonly controls polarity in epithelia, where cells tend to maintain close cell-to-cell contact. However, during vertebrate gastrulation, Wnt/PCP also influences polarity in mesenchymal cells that form transient cell contacts (Jessen et al., 2002; Marlow et al., 2002). Wnt/PCP signaling promotes polarized cell migration and rearrangements and coordinates this polarity with embryonic axes. These polarized movement behaviors include directed migration, mediolateral intercalation (Wallingford et al., 2000; Jessen et al., 2002) and polarized radial cell intercalation (Yin et al., 2008). Furthermore, oriented cell divisions also require Wnt/PCP signaling (Gong et al., 2004; Ciruna et al., 2006). Under the influence of Wnt/PCP signaling, cells elongate and align mediolaterally, and thus perpendicular to the AP gastrula axis. In addition, the direction and stability of protrusions, and movement direction of cells, are mediolaterally biased (Wallingford et al., 2000; Topczewski et al., 2001; Jessen et al., 2002; Montero et al., 2005). Mechanistically, Wnt/PCP signaling influences dynamic cohesion of anterior mesoderm cells (Montero et al., 2005), endocytosis of E-cadherin molecules (Ulrich et al., 2005), and the distribution of Fibronectin (Goto et al., 2005; Yin and Solnica-Krezel, 2007). Such striking polarization of cell behaviors suggests Wnt/PCP influences the microtubule (MT) cytoskeleton. Evidence implicates Wnt/PCP signaling in orienting the basal body in cochlea, floor plate of the neural tube, and epidermis, suggesting an interaction Development 138, 543-552 (2011) doi:10.1242/dev.053959 © 2011. Published by The Company of Biologists Ltd