PROTEOGLYCANS ARE REQUIRED FOR MAINTENANCE OF WNT-11 EXPRESSION IN THE URETER TIPS

Development of the metanephric kidney requires the concerted interacti on of two tissues, the epithelium of the ureteric duct and the metanep hric mesenchyme. Signals from the ureter induce the metanephric mesenc hyme to condense and proliferate around the ureter tip, reciprocal sig nals from the mesenchyme induce the meter tip to grow and to branch, W nt genes encode secreted glycoproteins, which are candidate mediators of these signaling events, We have identified three Wnt genes with spe cific, non-overlapping expression patterns in the metanephric kidney, Wnt-4, Wnt-7b and Wnt-11, Wnt-4 is expressed in the condensing mesench yme and the comma- and S-shaped bodies. Wnt-7b is expressed in the col lecting duct epithelium from 13.5 days post coitum onward, Wnt-11 is f irst expressed in the nephric duct adjacent to the metanephric blastem a prior to the outgrowth of the ureteric bud. Wnt-11 expression in Dan forth's short-tail mice suggests that signaling from the mesenchyme ma y regulate Wnt-11 activation. During metanephric development, Wnt-11 e xpression is confined to the tips of the branching meter. Maintenance of this expression is independent of Wnt-4 signaling and mature mesenc hymal elements in the kidney, Moreover, Wnt-11 expression is maintaine d in recombinants between ureter and lung mesenchyme suggesting that b ranching morphogenesis and maintenance of Wnt-11 expression are indepe ndent of metanephric mesenchyme-specific factors. Interference with pr oteoglycan synthesis leads to loss of Wnt-11 expression in the ureter tip, We suggest that Wnt-11 acts as an autocrine factor within the ure ter epithelium and that its expression is regulated at least in part b y proteoglycans.