In conclusion, the mammalian Pygo2 gene is required for normal branching morphogenesis of the ureteric bud, with mutants showing dilated tips and reduced numbers of tips. In addition, in Pygo2 mutants there was an expansion of the zone of metanephric mesenchyme that caps the ureteric buds. Nevertheless, nephron formation proceeded remarkably normally, even in Pygo1/Pygo2 double-homozygous mutants. This was surprising considering the importance of the Pygopus gene in canonical Wnt signaling in Drosophila, and the importance of canonical Wnt signaling in nephrogenesis. The results argue that the mammalian Pygopus genes are, in most developing systems, only quantitative transducers of Wnt signaling. Previous cell culture studies [32,33] and the reduced BAT-gal transgene reporter expression in the Pygo1/Pygo2 knockout mice described in this report, do confirm an evolutionarily conserved function in canonical Wnt signaling. In mammals, however, the phenotypic effects of Pygopus mutation are much milder than in Drosophila. The degree of importance of the Pyg1/2 genes in Wnt signaling was context-dependent, but in general, mammalian organogenesis remained intact in Pygopus mutants. Perhaps the simplest explanation is that in mammals, other genes show partial functional redundancy with the two Pygopus genes. The β-catenin transcription-factor complex includes a large and growing number of proteins , some of which may share the nuclear localization and/or transcription activation functions of Pygo1/Pygo2 in mammals. The identities and roles of these Pygopus redundant genes remain to be determined.