INTRODUCTION Polarity is a fundamental characteristic of most cells and is essential for their proper function. Cellular polarity has been intensively investigated, and significant progress has been made in revealing the mechanisms that underlie the establishment of cellular polarity. Another widespread, but less understood, form of polarity is planar polarity (PP), which is the organization of cells within the plane of the epithelium. Intensive recent investigations have demonstrated that a conserved PP pathway works to coordinate the polarity of adjacent cells in such divergent systems as convergent extension movements in zebrafish and frogs, and the polarity of wing hairs in the fly (Axelrod and McNeill, 2002). Studies primarily in the fly have implicated a Frizzled (Fz) signaling pathway as being central to the control of PP (Adler and Lee, 2001). Analysis of clones of fz mutant cells reveals both cell autonomous and non-autonomous defects in PP. This has led to the suggestion that Fz, a seven-pass transmembrane receptor (Adler et al., 1990; Park et al., 1994) is involved in both the reception of a PP signal and in its transmission to adjacent cells. Recent work has demonstrated that Fz is part of an asymmetrically localized signaling complex, which also contains the signaling protein Dishevelled and the atypical cadherin, Flamingo (Axelrod, 2001; Das et al., 2002; Strutt et al., 2002; Strutt, 2001; Tree et al., 2002; Usui et al., 1999). How Fz signaling activity is controlled is not clear. A well-studied system for understanding the control of PP is the fly eye (Wolff and Ready, 1993). The fly eye is composed of ~800 photoreceptor clusters called ommatidia, each composed of eight photoreceptors, R1-R8, as well as a number of accessory cells (Fig. 1A). Ommatidia are organized into dorsal and ventral fields of mirror-image planar polarity, which meet at the equator (Fig. 1A,C). PP develops in the eye imaginal disc shortly after ommatidial preclusters assemble. Preclusters in the dorsal and ventral fields rotate 90° in opposite directions away from the equator, producing mirror image fields. Genetic studies have suggested that fz is necessary for interpreting and communicating a PP signal that is thought to emanate from the equator. fz has also been implicated in controlling R3 cell fate (Zheng et al., 1995). Intensive work has suggested that photoreceptors R3 and R4 are crucial in directing the rotation of preclusters. In addition it has been shown that the member of the R3/R4 pair with higher Notch activity will take on the R4 fate. This decision directs precluster rotation (Cooper and Bray, 1999; Fanto and Mlodzik, 1999; Tomlinson and Struhl, 1999). The atypical cadherins Fat (Ft) and Dachsous (Ds) act upstream of fz, and may control Fz activity during the development of PP. Two separate models have been proposed to explain how Fat and Ds control planar polarity in the eye. 763 Development 130, 763-774 © 2003 The Company of Biologists Ltd doi:10.1242/dev.00304 Fat is an atypical cadherin that controls both cell growth and planar polarity. Atrophin is a nuclear co-repressor that is also essential for planar polarity; however, it is not known what genes Atrophin controls in planar polarity, or how Atrophin activity is regulated during the establishment of planar polarity. We show that Atrophin binds to the cytoplasmic domain of Fat and that Atrophin mutants show strong genetic interactions with fat. We find that both Atrophin and fat clones in the eye have non-autonomous disruptions in planar polarity that are restricted to the polar border of clones and that there is rescue of planar polarity defects on the equatorial border of these clones. Both fat and Atrophin are required to control four-jointed expression. In addition our mosaic analysis demonstrates an enhanced requirement for Atrophin in the R3 photoreceptor. These data lead us to a model in which fat and Atrophin act twice in the determination of planar polarity in the eye: first in setting up positional information through the production of a planar polarity diffusible signal, and later in R3 fate determination. Key words: Planar polarity, Adhesion, Drosophila, Eye, Atrophin, Fat SUMMARY The tumor-suppressor and cell adhesion molecule Fat controls planar polarity via physical interactions with Atrophin, a transcriptional co-repressor Manolis Fanto 1 , Lesley Clayton 1 , Jamie Meredith 1 , Kirsten Hardiman 1 , Bernard Charroux 2 , Stephen Kerridge 2 and Helen McNeill 1, * 1 Cancer Research UK (ICRF), London Research Institute, 44 Lincoln’s Inn Fields, London WC2A 3PX, UK 2 Laboratoire de Génétique et Physiologie du Développement, CNRS-INSERM-Université de la Méditerranée-AP de Marseille, Campus de Luminy Case 907, F-13288 Marseille, Cedex 09, France *Author for correspondence (e-mail: helen.mcneill@cancer.org.uk) Accepted 7 November 2002