The zebrafish pronephros: a genetic system for studies of kidney development

The zebrafish, as a model system for vertebrate development, offers distinc t experimental advantages for studies of organogenesis. The simplicity of t he zebrafish pronephros, the feasibility of isolating large numbers of muta nts, and the growth in infrastructure for genomics makes the zebrafish an a ttractive system for the analysis of kidney development. Mutants affecting several aspects of nephrogenesis, including differentiation of the intermed iate mesoderm, nephron patterning, epithelial polarity, and angiogenesis, h ave been isolated. Analysis of mutant phenotypes and the cloning of mutant genes has revealed: (1) a role for bone morphogenetic proteins in patternin g the ventral mesoderm, (2) an essential role for the pax2.1 gene in pronep hric develop ment, (3) multiple loci required for establishing epithelial p olarity in the pronephric duct, (4) a central role for podocytes in directi ng glomerulogenesis, and (5) 15 loci associated with cystic maldevelopment in the pronephros. The striking similarities of pronephric cell types to th ose found in higher vertebrates, as well as the conservation of kidney-spec ific gene expression patterns, suggest that insights gained from studies in zebrafish will be broadly applicable to cell differentiation in the kidney .