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Fig. 3. GDNF regulates kidney development. GDNF (red) is expressed by the metanephric mesenchyme, and RET (green) by the Wolffian duct, from which the ureteric budding is promoted by GDNF. When the tip of the bud has induced two subsets of mesenchymal cells for epithelial differentiation, these cells strongly upregulate GDNF. This leads to formation of a double-gradient of GDNF around the ureteric tip and its branching.