Journal of Cell Science, Supplement 17, 171-181 (1993) Printed in Great Britain © The Company of Biologists Limited 1993 171 Apical junctions and cell signalling in epithelia Daniel F. Woods and Peter J. Bryant Developmental Biology Center, University of California, Irvine, CA 92717, USA SUMMARY Genetic analysis in Drosophila has led to the identifica tion of several proteins that mediate cell-cell interactions controlling the fate and proliferation of epithelial cells. These proteins are localized or enriched in the adherens and septate junctions at the apical end of the lateral membranes between cells. The proteins localized or enriched at adherens junctions include Notch, which is important for the cell interactions controlling neuro blast and bristle patterning; Boss and sevenless, which are required for the cell interaction that establishes the R7 photoreceptor cell; and Armadillo, required for the wingless-dependent cell interactions that control seg ment polarity and imaginal disc patterning. Proteins localized at septate junctions include the product of the tumor suppressor gene dig, which is required for sep tate junction formation, apical basal cell polarity, and the cell interactions that control proliferation. The results suggest that the cell signalling events important for cell fate determination and for cell proliferation con trol in epithelia occur at the apical junctions. The migra tion of the nucleus to the apical surface of the epithe lium for mitosis may enable it to interact directly with the junction-associated signalling mechanisms. Key words: adherens junction, septate junction, epithelial cell, mitosis, pattern formation, imaginal disc, ommatidia, Drosophila INTRODUCTION Epithelial cell layers protect the organism from its envi ronment, separate different compartments of the organism, transport materials from one compartment to another, and produce both liquid- and solid-phase extracellular compo nents of the body. These functions depend upon the phys ical integrity and impermeability of the epithelial sheet, and on the apical-basal polarity of its constituent cells. The spe cialized junctions that are formed between adjacent epithe lial cells are critical to epithelial properties: they provide a strong physical attachment between cells, they provide a tight barrier to transepithelial movement of molecules and ions, and they restrict mobile membrane proteins to either the apical or the basal-lateral membrane domain, thus con tributing to apical-basal cell polarity (Rodriguez-Boulan and Nelson, 1989). These functions of specialized junctions have been revealed by molecular, physiological and cell biological studies. However, evidence from genetic analy sis is now suggesting an additional and critically important role of apical cell junctions in the development of epithe lial cell populations. These structures appear to mediate the interactions between cells and their neighbors that control both cell proliferation and the formation of spatial patterns of differentiation. Intercellular junctions of vertebrate epithelial cells include, in apical-basal order (Fig. 1): tight junctions (also called occluding junctions or zonulae occludens), adherens junctions (also called belt desmosomes or zonulae adherens), both of which form belts around the apical end of the cell, as well as gap junctions and desmosomes scat tered along the lateral membrane basal to the adherens junc tions (Rodriguez-Boulan and Nelson, 1989). In arthropods the tight junction is missing, but an additional junction, the septate junction, is found basal to the adherens junction (Figs 1 and 2). Interactions between epithelial cells and their neighbors control cell proliferation, differentiation and morphogen esis, and these interactions must take place via the un specialized lateral membrane or via the specialized junc tions listed above. At the present state of knowledge any or all of the specialized junctions connecting epithelial cells could be involved in these cell interactions. Most investi gations of cell communication have been focused on gap junctions, at least in part because simple physiological tests for their function are available. However, an increasing volume of evidence points to the apical junctions as the sites of developmentally significant cell interactions. Much of this evidence comes from immunolocalization of pro teins identified by genetic analysis in Drosophila, and a summary of the locations of these proteins is presented in Table 1. MOLECULAR NATURE AND POSSIBLE FUNCTIONS OF APICAL JUNCTIONS Adherens junctions The adherens junction is a thick density that forms a con tinuous belt around the apical end of each epithelial cell