Induction of Nephrogenic Mesenchyme by Osteogenic Protein 1 (Bone Morphogenetic Protein 7)

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 93; no. 17; pp. 9021 - 9026
• Main Authors: Vukicevic, Slobodan, Kopp, Jeffrey B., Luyten, Frank P., Sampath, T. Kuber
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 20.08.1996; National Acad Sciences; National Academy of Sciences
• Subjects: Animals; Antisense oligonucleotides; Base Sequence; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Condensation; Developmental biology; Epithelium; Gene Expression; Human growth; In Vitro Techniques; Kidney - embryology; Kidney Tubules - embryology; Kidneys; Mesoderm - drug effects; Messenger RNA; Mice; Molecular Sequence Data; Morphogenesis - drug effects; Oligonucleotides; Proteins - antagonists & inhibitors; Proteins - genetics; Proteins - pharmacology; RNA; RNA, Messenger - analysis; Spinal cord; Time Factors; Tissue Distribution; Transforming Growth Factor beta - antagonists & inhibitors; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - pharmacology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.93.17.9021

The definitive mammalian kidney forms as the result of reciprocal interactions between the ureteric bud epithelium and metanephric mesenchyme. As osteogenic protein 1 (OP-1/bone morphogenetic protein 7), a member of the TGF-β superfamily of proteins, is expressed predominantly in the kidney, we examined its involvement during metanephric induction and kidney differentiation. We found that OP-1 mRNA is expressed in the ureteric bud epithelium before mesenchymal condensation and is subsequently seen in the condensing mesenchyme and during glomerulogenesis. Mouse kidney metanephric rudiments cultured without ureteric bud epithelium failed to undergo mesenchymal condensation and further epithelialization, while exogenously added recombinant OP-1 was able to substitute for ureteric bud epithelium in restoring the induction of metanephric mesenchyme. This OP-1-induced nephrogenic mesenchyme differentiation follows a developmental pattern similar to that observed in the presence of the spinal cord, a metanephric inducer. Blocking OP-1 activity using either neutralizing antibodies or antisense oligonucleotides 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 demonstrate that OP-1 is required for metanephric mesenchyme differentiation and plays a functional role during kidney development.