Members of the Wnt family of secreted signalling proteins play many crucial roles during embryonic development. Wnt signalling is negatively regulated by secreted Frizzled-related proteins (sFRPs), which bind to Wnts extracellularly, but now, on p. , Yusuke Mii and Masanori Taira report that the sFRPs Frzb and Crescent (Cres) can expand the signalling range of Wnts by enhancing their diffusion. By microinjecting mRNAs for tagged versions of Wnt8, Wnt11, Frzb or Cres into Xenopus embryos, the researchers show that Wnts do not diffuse effectively, whereas sFRPs spread widely. However, they report, the expression of an sFRP and a tagged Wnt in the same blastomere or in separate oocytes that are then co-cultured promotes Wnt diffusion. Most importantly, Wnt8 conveyed by sFRPs activates Wnt signalling at a distance from its source in vitro and in vivo, even though sFRPs usually act as Wnt inhibitors. Overall, these results provide new insights into how the range of Wnt signalling is regulated in vertebrates.
