sFRP-2 is a target of the Wnt-4 signaling pathway in the developing metanephric kidney

Members of the Wnt family of secreted glycoproteins act as short-range sign aling molecules in vertebrate embryogenesis. Previous work, has shown that Wnt-4 is required for kidney development. Mice lacking functional Wnt-4 fai l to form pretubular cell aggregates. Wnt-4 acts as an autoinducer of the m esenchymal to epithelial transition underlying nephron development. We have identified a member of the gene family encoding secreted frizzled related proteins (sFRP), putative Wnt antagonists, that shows overlapping expressio n with Wnt-4 in aggregating mesenchyme and simple epithelial bodies during metanephric development. sFRP-2 expression is absent in metanephric mesench yme of kidneys mutant for Wnt-4 and is coinduced with Wnt-4 in isolated met anephric mesenchyme by cells expressing Wnt-4, The cysteine-rich domain of sFRP-2 binds to Wnt-4 as shown by coimmunoprecipitation experiments. Hence, sFRP-2 is a target of the Wnt-4 signaling pathway in the metanephric kidne y and may modulate Wnt-4 signaling. sFRP-2 expression is highly dynamic and specific during other aspects of embryogenesis, sFRP-2 is expressed in sub populations of ependymal cells in spinal cord and brain, in the developing eye, in limb bud mesenchyme, in the heart, and strongly in skeletogenic con densations of facial bones, suggesting widespread interaction with other me mbers of the Wnt gene family during embryogenesis. Dev. Dyn. 1998;213:440-4 51, (C) 1998 Wiley-Liss, Inc.