Development 110, 105-114 (1990) Printed in Great Britain © The Company of Biologists Limited 1990 105 The Drosophila segment polarity gene patched is involved in a position- signalling mechanism in imaginal discs ROGER G. PHILLIPS 1 , IAN J. H. ROBERTS 1 , PHILIP W. INGHAM 2 and J. ROBERT S. WHITTLE 1 1 School of Biological Sciences, University of Sussex, Brighton, BN1 9QG, UK 2 Molecular Embryology Laboratory, ICRF Developmental Biology Unit, South Parks Road, Oxford, OX1 3PS, UK Summary We demonstrate the role of the segment polarity gene patched (ptc) in patterning in the cuticle of the adult fly. Genetic mosaics of a lethal allele of patched show that the contribution of patched varies in a position-specific manner, defining three regions in the wing where ptc clones, respectively, behave as wild-type cells, affect vein formation, or are rarely recovered. Analysis of twin clones demonstrates that the reduced clone frequency results from a proliferation failure or cell loss. In the region where clones upset venation, they autonomously fail to form veins and also non-autonomously induce ectopic veins in adjacent wild-type cells. In heteroallelic combinations with lethal alleles, two viable alleles pro- duce distinct phenotypes: (1) loss of structures and mirror-image duplications in the region where patched clones fail to proliferate; (2) vein abnormalities in the anterior compartment. We propose that these differ- ences reflect independently mutable functions within the gene. We show the pattern of patched transcription in the developing imaginal wing disc in relation to the expression of certain other reporter genes using a novel double-labelling method combining non-radioactive de- tection of in situ hybridization with /3-galactosidase detection. The patched transcript is present throughout the anterior compartment, with a stripe of maximal intensity along the A/P compartment border extending into the posterior compartment. We propose that the patched product is a component of a cell-to-cell position- signalling mechanism, a proposal consistent with the predicted structure of the patched protein. Key words: imaginal discs, pattern formation, cell communication, segment polarity, patched, Drosophila. Introduction The body of the Drosophila adult is derived from a series of embryonic primordia (imaginal discs) which undergo extensive rounds of cell division during the larval stages of development (Auerbach, 1936; Noth- iger, 1972). Although these cells receive instructions about their segmental identity during embryogenesis (Akam, 1987; Peifer et al. 1987), clonal analysis has shown that their early lineage, with the exception of the anterior-posterior compartmentalisation event (Gar- cia-Bellido et al. 1973), is largely indeterminate (Gar- cia-Bellido and Merriam, 1971; Bryant, 1970). The information required for the patterning of cells in different structures is thus an emergent property, which presumably depends upon communication between cells as they proliferate. A large body of data shows that imaginal disc cells respond to changes in the identity of neighbouring cells whether these alterations are made by surgical or genetic changes (reviewed in Whittle, 1990). When normally distant parts of a mature wing disc are juxtaposed and allowed to proliferate, the intervening pattern of cell types is regenerated by a process known as intercalation (Haynie and Bryant, 1976). In some genetic mosaics, wild-type cells respond to neighbours of changed genotype by differentiating cell types in changed patterns (Stern, 1956; Simpson and Schneiderman, 1975; Mohler, 1988; Santamaria et al. 1989) or polarities (Gubb and Garcia-Bellido, 1982; Vinson and Adler, 1987). In contrast to the early events of embryonic patterning (Ingham, 1988), virtually nothing is known about the molecular basis of this process. Amongst the many mutations that disrupt adult morphogenesis are viable alleles of some of the segment polarity genes, a class originally defined by embryonic lethal mutations (Niisslein-Volhard and Weischaus, 1980; Niisslein-Volhard et al. 1984). An increasing body of evidence has implicated these genes in cell interac- tions (Martinez-Arias et al. 1988; DiNardo et al. 1988; Mohler, 1988). Here we show that mutations of the segment polarity gene patched (ptc) disrupt cell pattern- ing in the cuticle of the adult fly. Using genetic mosaics of patched we find a requirement for this gene in cells in specific regions of the wing, which is not rescued by neighbouring cells; moreover in some locations the effects of patched mutations extend beyond the limit of the mosaic, suggesting a role for the gene in a signal