INDUCTION OF NEPHROGENIC MESENCHYME BY OSTEOGENIC PROTEIN-1 (BONE MORPHOGENIC PROTEIN-7)

The definitive mammalian kidney forms as the result of reciprocal inte ractions between the ureteric bud epithelium and metanephric mesenchym e, As osteogenic protein 1 (OP-1/bone morphogenetic protein 7), a memb er of the TGF-beta superfamily of proteins, is expressed predominantly in the kidney, we examined its involvement during metanephric inducti on and kidney differentiation. We found that OP-1 mRNA is expressed in the ureteric bud epithelium before mesenchymal condensation and is su bsequently seen in the condensing mesenchyme and during glomerulogenes is, Mouse kidney metanephric rudiments cultured without ureteric bud e pithelium failed to undergo mesenchymal condensation and further epith elialization, while exogenously added recombinant OP-1 was able to sub stitute for ureteric bud epithelium in restoring the induction of meta nephric mesenchyme. This OP-1-induced nephrogenic mesenchyme different iation follows a developmental pattern similar to that observed in the presence of the spinal cord, a metanephric inducer. Blocking OP-1 act ivity using either neutralizing antibodies or antisense oligonucleotid es in mouse embryonic day 11.5 mesenchyme, cultured in the presence of metanephric inducers or in intact embryonic day 11.5 kidney rudiment, greatly reduced metanephric differentiation. These results demonstrat e that OP-1 is required for metanephric mesenchyme differentiation and plays a functional role during kidney development.