A new secreted protein that binds to Wnt proteins and inhibits their activities

The Wnt proteins constitute a large family of extracellular signalling mole cules that are found throughout the animal kingdom and are important for a wide variety of normal and pathological developmental processes(1,2). Here we describe Wnt-inhibitory factor-1 (WIF-1), a secreted protein that binds to Wnt proteins and inhibits their activities. WIF-1 is present in fish, am phibia and mammals, and is expressed during Xenopus and zebrafish developme nt in a Complex pattern that includes paraxial presomitic mesoderm, notocho rd, branchial arches and neural crest derivatives. We use Xenopus embryos t o show that WIF-1 overexpression affects somitogenesis (the generation of t runk mesoderm segments), in agreement with its normal expression in paraxia l mesoderm. In vitro, WIF-1 binds to Drosophila Wingless and Xenopus Wnt8 p roduced by Drosophila S2 cells. Together with earlier results obtained with the secreted Frizzled-related proteins(1.2), our results indicate that Wnt proteins interact with structurally diverse extracellular inhibitors, pres umably to fine-tune the spatial and temporal patterns of Wnt activity.