This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Acute renal failure is a significant cause of morbidity with limited therapeutic options, and it is anticipated that the field of regenerative medicine will provide therapies to meet this need. Bone Morphogenetic Proteins (BMPs) are particularly interesting candidates as they regulate embryonic nephron formation, and because their use is already FDA approved for other applications, removing a significant obstacle to translation. Our work focuses on mechanistically understanding the control of nephron development by BMPs in vivo with the goals of: i) Identifying molecular pathways activated by BMPs, and ii) Identifying novel drug targets. During the funding period, we have made significant advances in understanding developmental requirements for different BMP cytokines (Oxburgh et al. Dev Biol 2005, 286:637-46), and their genomic regulation (Adams et al. Dev Biol 2007, 311:679-690). Using an in vivo BMP reporter mouse strain generated specifically for this purpose, we have for the first time created a map of signaling activity at the cellular level during nephron development (Blank et al, BMC Dev Biol, submitted). To explore novel findings made in this analysis, we have devised a culture system that reproduces the zone of active nephrogenesis in the developing kidney. Through screening we have identified two candidate BMP modulators in the injured kidney, Chordin like 1 and Follistatin like 1 (Adams et al. Gene Expr Patterns 2007, 7:491-500). A separate series of investigations aimed at understanding the roles of these molecules in the regenerative response to injury are proposed in our renewal application.
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