Neural anteroposterior (AP) patterning requires numerous signalling molecules, including the Wnts. But how are these many signals integrated? On , Itasaki et al. tackle this question by performing a functional screen for activities that alter the AP character of Xenopus animal caps, which have been neuralised with noggin RNA. They report the isolation of Wise (for Wnt modulator in surface ectoderm) from this screen, a novel, secreted cysteine knot factor that can activate or inhibit Wnt signalling in a context-dependent manner. For example, in an animal cap assay, Wise can induce posterior neural markers by activating the Wnt signalling pathway. By contrast, in an assay for secondary axis induction, Wise inhibits Wnt signalling. These results, together with data showing that Wise and Wnt8 compete for binding to LRP6, a Wnt co-receptor, add a new dimension to our understanding of Wnt signalling during development.
