DF/HCC Program Affiliation

Cancer Genetics

Research Abstract

Our research focuses on kidney development and the regulation of renal cell
differentiation. The zebrafish, as a model system for vertebrate
organogenesis, offers many experimental advantages for studies of kidney
development. Large scale mutant screens taking advantage of the optical
transparency of zebrafish embryos have isolated many mutants with kidney
defects. Our analysis of the mutant no isthmus, which carries mutations in
the zebrafish pax2.1 gene, has revealed an essential role for pax2.1 in
pronephric tubule development and for restricting Wilms tumor suppressor
(wt1) gene expression to developing podocytes. Further studies are aimed at studying genes that function earlier than pax2.1 and may regulate its expression. A large group of mutants show defects in
the development of epithelial polarity and subsequent development of cysts
in the pronephros. We have positionally cloned two of these genes and found that they function in epithelial cilia and in membrane protein trafficking. We are also studying homologs of human autosomal dominant polycystic kidney disease genes and their role in normal kidney function. Finally we have used the zebrafish to define the function of a novel podocyte gene that is essential for cell junction formation.

Publications

• Liu Y, Pathak N, Kramer-Zucker A, Drummond IA.Notch signaling controls the differentiation of transporting epithelia and multiciliated cells in the zebrafish pronephros.Development 2007 Mar;134(6):1111-22.
  17287248
• Panizzi JR, Jessen JR, Drummond IA, Solnica-Krezel L.New functions for a vertebrate Rho guanine nucleotide exchange factor in ciliated epithelia.Development 2007 Mar;134(5):921-31.
  17267448
• Hinkes B, Wiggins RC, Gbadegesin R, Vlangos CN, Seelow D, Nurnberg G, Garg P, Verma R, Chaib H, Hoskins BE, Ashraf S, Becker C, Hennies HC, Goyal M, Wharram BL, Schachter AD, Mudumana S, Drummond I, Kerjaschki D, Waldherr R, Dietrich A, Ozaltin F, Bakkalo
  17086182
• Obara T, Mangos S, Liu Y, Zhao J, Wiessner S, Kramer-Zucker AG, Olale F, Schier AF, Drummond IA.Polycystin-2 immunolocalization and function in zebrafish.J Am Soc Nephrol 2006 Oct;17(10):2706-18.
  16943304
• Sayer JA, Otto EA, O'Toole JF, Nurnberg G, Kennedy MA, Becker C, Hennies HC, Helou J, Attanasio M, Fausett BV, Utsch B, Khanna H, Liu Y, Drummond I, Kawakami I, Kusakabe T, Tsuda M, Ma L, Lee H, Larson RG, Allen SJ, Wilkinson CJ, Nigg EA, Shou C, Lillo C,
  16682973
• Kramer-Zucker AG, Wiessner S, Jensen AM, Drummond IA.Organization of the pronephric filtration apparatus in zebrafish requires Nephrin, Podocin and the FERM domain protein Mosaic eyes.Dev Biol 2005 Sep 15;285(2):316-29.
  16102746
• Kramer-Zucker AG, Olale F, Haycraft CJ, Yoder BK, Schier AF, Drummond IA.Cilia-driven fluid flow in the zebrafish pronephros, brain and Kupffer's vesicle is required for normal organogenesis.Development 2005 Apr;132(8):1907-21.
  15790966
• Drummond IA.Zebrafish kidney development.Methods Cell Biol 2004;76:501-30.
  15602890
• Drummond IA, Majumdar A, Hentschel H, Elger M, Solnica-Krezel L, Schier AF, Neuhauss SC, Stemple DL, Zwartkruis F, Rangini Z, Driever W, Fishman MC.Early development of the zebrafish pronephros and analysis of mutations affecting pronephric function.Devel
  9806915