The goal of this program project is to understand the nature of the pathways and processes that pattern the kidney epithelium into its terminally differentiated phenotype. Project 1 attempts to identify modifier loci in mice with targeted mutations in polycystin 1. Project 2 proposes to elucidate the molecular pathways that underlie the role of polycystin 1 in epithelial differentiation. Project 3 plans to characterize novel transcription factors thought to regulate renal tubulogenesis in vitro. Project 4 seeks to understand the genetic and physiologic factors influencing the course of cyst formation in Zebrafish. Project 5 seeks to understand the genetic and physiologic factors influencing the course of cyst formation in zebrafish. Project 5 intends to derive the three-dimensional structures of key domains in polycystin 1 and 2. Each of the projects is likely to yield fundamental insight into the biology of cyst formation, and provide new targets for therapeutic intervention. The objectives of this proposal and their common emphasis on molecular mechanisms invite a high degree of collaborative interactions and conceptual synergy best served by the program project format.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Program Projects (P01)
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Special Emphasis Panel (ZDK1-GRB-4 (O2))
Program Officer
Rasooly, Rebekah S
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Massachusetts General Hospital
United States
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Drummond, Iain A (2011) Polycystins, focal adhesions and extracellular matrix interactions. Biochim Biophys Acta 1812:1322-6
Mangos, Steve; Lam, Pui-ying; Zhao, Angela et al. (2010) The ADPKD genes pkd1a/b and pkd2 regulate extracellular matrix formation. Dis Model Mech 3:354-65
Moller, Clemens C; Mangos, Steve; Drummond, Iain A et al. (2008) Expression of trpC1 and trpC6 orthologs in zebrafish. Gene Expr Patterns 8:291-6
Mangos, Steve; Liu, Yan; Drummond, Iain A (2007) Dynamic expression of the osmosensory channel trpv4 in multiple developing organs in zebrafish. Gene Expr Patterns 7:480-4
Pathak, Narendra; Obara, Tomoko; Mangos, Steve et al. (2007) The zebrafish fleer gene encodes an essential regulator of cilia tubulin polyglutamylation. Mol Biol Cell 18:4353-64
Obara, Tomoko; Mangos, Steven; Liu, Yan et al. (2006) Polycystin-2 immunolocalization and function in zebrafish. J Am Soc Nephrol 17:2706-18
Kramer-Zucker, Albrecht G; Olale, Felix; Haycraft, Courtney J et al. (2005) Cilia-driven fluid flow in the zebrafish pronephros, brain and Kupffer's vesicle is required for normal organogenesis. Development 132:1907-21
Drummond, Iain A (2005) Kidney development and disease in the zebrafish. J Am Soc Nephrol 16:299-304
Li, Zhixing; Stuart, Robert O; Eraly, Satish A et al. (2003) Debt91, a putative zinc finger protein differentially expressed during epithelial morphogenesis. Biochem Biophys Res Commun 306:623-8
Xu, G Mark; Gonzalez-Perrett, Silvia; Essafi, Makram et al. (2003) Polycystin-1 activates and stabilizes the polycystin-2 channel. J Biol Chem 278:1457-62

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