The four-jointed gene is required in the Drosophila eye for ommatidial polarity specification

Background: The Drosophila eye is composed of about 800 ommatidia, each of which becomes dorsoventrally polarised in a process requiring signalling th rough the Notch, JAK/STAT and Wingless pathways. These three pathways are t hought to act by setting up a gradient of a signalling molecule (or molecul es) often referred to as the 'second signal'. Thus far, no candidate for a second signal has been identified. Results: The four-jointed locus encodes a type II transmembrane protein tha t is expressed in a dorsoventral gradient in the developing eye disc, We ha ve analysed the function and regulation of four-jointed during eye patterni ng. Loss-of-function clones or ectopic expression of four-jointed resulted in strong non-autonomous defects in ommatidial polarity on the dorsoventral axis. Ectopic expression experiments indicated that localised four-jointed expression was required at the time during development when ommatidial pol arity was being determined. In contrast, complete removal of four-jointed f unction resulted in only a mild ommatidial polarity defect. Finally, we fou nd that four-jointed expression was regulated by the Notch, JAK/STAT and Wi ngless pathways, consistent with it mediating their effects on ommatidial p olarity. Conclusions: The clonal phenotypes, time of requirement and regulation of f our-jointed are consistent with it acting in ommatidial polarity determinat ion as a second signal downstream of Notch, JAK/STAT and Wingless. Interest ingly, it appears to act redundantly with unknown factors in this process, providing an explanation for the previous failure to identify a second sign al.