Fig. 1.

Reciprocal interactions between the metanephric mesenchyme and the ureteric bud are required for kidney development. (A) GDNF and Ret signaling are required for outgrowth of the ureteric bud into the metanephric mesenchyme. (B) Ret-GDNF, Sprouty, Slit-Robo, fibroblast growth factors (FGFs), bone morphogenetic proteins (BMPs), sonic hedgehog (Shh), and angiotensin receptor 2 signaling pathways regulate ureteric bud branching. Mutations in Ret-GDNF, Robo2, and Shh, and variants in the renin–angiotensin system contribute to human CAKUT.