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

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