Loss of are function results in a downwardly curved wing and smaller eyes with a reduced number of ommatidia. Consistent with this phenotype, molecular analysis shows that are mRNA and protein are expressed in the wing imaginal disc and in clusters of cells in the morphogenetic furrow of the eye imaginal disc. The 36-kb are transcription unit contains 10 exons that are spliced to form a 5.5-kb mRNA. The encoded Are protein is 143,000 Da and contains two PDZ (PSD-95, Discs large, ZO-1) domains; there is no close structural similarity to other PDZ proteins. In addition to its expression in imaginal discs, are is expressed during embryogenesis in epithelia undergoing morphogenesis, including the invaginating posterior midgut, evaginating Malpighian tubule buds, elongating hindgut, invaginating salivary glands, intersegmental grooves, and developing tracheae. Are. protein colocalizes with Armadillo (beta-catenin) to the apical (luminal) surface of these developing epithelia, indicating that it is associated with adherens junctions. Genes that are required for patterning of embryonic epithelia (e.g., tailless, Kruggel, fork head, and brachyenteron) or for progression of the morphogenetic furrow (i. e., hedgehog) are required to establish or maintain the regional expression of are. Misexpression of are in the eye imaginal discs results in rough and larger eyes with fused ommatidia. We propose that are affects eye development by modulating adherens junctions of the developing ommatidium. (C) 2000 Academic Press.