Jcb_201408039 1..9

Correspondence to Danelle Devenport: [email protected] Abbreviations used in this paper: A-P, anterior–posterior; CE, convergent extension; Dgo, Diego; Ds, Dachsous; Dsh, Dishevelled; Fj, Four-jointed; Fmi, Flamingo; Ft, Fat; Fz, Frizzled; MT, microtubule; PCP, planar cell polarity; Pk, Prickle; TGN, trans-Golgi network; Vang, Van Gogh; Wg, Wingless. The collective alignment of cell polarity across the tissue plane is a phenomenon known as planar cell polarity (PCP). Exemplified by the uniform orientation of bristles covering the insect epidermis or of the hairs covering the mammalian body surface (Fig. 1 A), PCP patterns can align over thousands, even billions of cells. This phenomenon is controlled by the so-called PCP pathway, which integrates global directional cues to produce locally polarized cell behaviors. There has been a recent surge in interest in PCP after discoveries that various processes such as vertebrate gastrulation, mammalian ear patterning and hearing, and neural tube closure all require a conserved set of PCP genes (Heisenberg et al., 2000; Tada and Smith, 2000; Wallingford et al., 2000; Kibar et al., 2001; Murdoch et al., 2001; Curtin et al., 2003; Montcouquiol et al., 2003; Copley et al., 2013). Since that time, the PCP pathway has been found to coordinate cell behaviors in numerous diverse settings including polarized ciliary beating in the trachea and brain ventricles (Tissir et al., 2010; Vladar et al., 2012), oriented cell divisions (Gong et al., 2004; Baena-López et al., 2005; Ségalen et al., 2010; Mao et al., 2011), lung branching (Yates et al., 2010), and hair follicle alignment (Guo et al., 2004; Devenport and Fuchs, 2008), to name a few (Fig. 1). Genetic disruptions to PCP cause severe developmental abnormalities in vertebrates, notably neural tube defects, left/right patterning defects, and ciliopathies, which highlights the essential requirement for PCP in development (Kibar et al., 2001; Murdoch et al., 2001; Curtin et al., 2003; Wang et al., 2006a,b; Kim et al., 2010; Song et al., 2010). Like many types of cell polarity, the establishment of PCP involves (1) a global orienting cue, (2) asymmetric segregation of dedicated polarity proteins, and (3) translation of polarity information into polarized outputs. But unlike other types of cell polarity, the PCP mechanisms we currently understand involve coupling between adjacent cells, allowing for the alignment of polarity over many cell distances. First described in insects and then genetically dissected in Drosophila melanogaster, PCP was long confined to the realm of experimental embryology and genetics until the discovery that the protein products of several PCP genes were localized asymmetrically within the cell, thrusting PCP into the domain of cell biology (for review see Strutt and Strutt, 2009). The challenge to understanding PCP on a molecular level is that long-range PCP is, in essence, an in vivo phenomenon that is difficult to recapitulate in a tissue culture dish. However, recent advances in imaging technology combined with increasingly sophisticated genetic tools are helping us to decipher the in vivo cell biology of PCP. In this review, I highlight some of the recent advances made toward understanding the cell biology underlying the establishment of coordinated polarized cell behaviors. For clarity, I limit discussions of PCP phenomena that meet the definition of PCP proposed by Goodrich and Strutt (2011): namely, that “cell–cell communication causes two or more cells to adopt coordinated polarity” in a process that is mechanistically “dependent upon planar polarity proteins.” Other aligned cellular patterns or examples of noncanonical Wnt signaling, sometimes described as “Wnt/PCP” signaling, will not be discussed.