This project aims to gain further insight into the role of Bone Morphogenetic Protein 7 (BMP7) during organogenesis of the mammalian eye and kidney. Although the BMP7 gene is expressed early in development in critical areas including the notochord, AER of the limb, and the developing heart, a null mutation of the BMP7 gene causes defects specifically in the eye and kidney. These data suggest that BMP7 plays a major role during inductive tissue interactions for maintenance and growth of these tissues. In this proposal both in vivo and in vitro approaches will be used to further investigate the function of BMP7 in the developing eye and kidney. BMP7-deficient kidney components will be combined with wild type components to identify tissue interactions that regulate BMP7 expression. BMP7 mutant ES cells will be used to create chimeric mice and used to establish in vivo whether BMP7 signals in an autocrine or paracrine fashion. Finally, a BMP7/LacZ line of mice has been established and will be used to allow a more sensitive method of detecting BMP7 expression domains and to identify genetic and molecular interactions that regulate BMP7 signaling. The proposed investigations aim to evaluate contributions of BMP7 to cell survival, proliferation and differentiation during kidney and eye development. These signaling pathways closely resemble those promoting tumor cell growth in vivo. Overall, results of these experiments will further our understanding of the molecular basis of mammalian eye and kidney organogenesis.
