A road to kidney tubules via the Wnt pathway

Classical in vitro studies indicate that tubule induction in the kidney mesenchyme is mediated by cell-cell contacts between the inducer tissue and the metanephric mesenchyme. Induction is completed within the first 24 h, after which tubules will form because of stimulated cell proliferation, migration, and cell adhesion. Recent evidence has revealed an essential role for the secreted signals from the Wnt gene family. Of these, Wnt-4 is expressed in developing tubules and knocking out its function perturbed kidney development. More detailed studies demonstrated normal condensation, but tubules were missing. Subsequent experiments indicated that Wnt-4 is also a sufficient signal to trigger tubulogenesis. Cells that were engineered to express Wnt-4 not only induced tubulogenesis in the kidney mesenchyme of Wnt-4 mutant embryos, but also induced tubules in the wild type mesenchyme. With the transfilter induction assay, Wnt-4-mediated induction was completed within the first 24 h, depending on the presence of proteoglycans and cell-cell contacts between the interactants. In addition, Wnt-4 autoinduced expression of its own gene and a panel of other components of the Wnt signalling pathway, such as frizzleds and a candidate Wnt antagonist from the secreted frizzled-related protein family. Taken together, the data provide evidence of an essential role for Wnt signal transmission and transduction pathways in the induction of kidney tubules, and the findings have paved the way for detailed molecular studies.