TGF beta 2, LIF and FGF2 cooperate to induce nephrogenesis

The metanephric kidney develops from interactions between the epithelial ur eteric bud and adjacent metanephric mesenchyme, which is induced by the bud to form the epithelia of the nephron, We have found that leukemia inhibito ry factor (LIF) and transforming growth factor beta2 (TGF beta2) are secret ed by inductive rat bud cells and cooperate to enhance and accelerate renal tubule formation in uninduced rat metanephric mesenchymal explants. LIF al one or TGF beta2 with fibroblast growth factor 2 induced numerous tubules i n isolated mesenchymes over an 8 day period, while (in combination) all thr ee caused abundant tubule formation in 72 hours. Furthermore, neutralizatio n of Wnt ligands with antagonist-secreted Frizzled-related protein 1 abroga ted these responses and combinatorial cytokine/growth factor stimulation of explants augmented nuclear activation of Tcf1/Lef1, suggesting that LIF an d TGF beta2/FGF2 cooperate to regulate nephrogenesis through a common Wnt-d ependent mechanism.