FRZB, A SECRETED PROTEIN EXPRESSED IN THE SPEMANN ORGANIZER, BINDS AND INHIBITS WNT-8

We isolated a Xenopus homolog of Frzb, a newly described protein conta ining an amino-terminal Frizzled motif. It dorsalized Xenopus embryos and was expressed in the Spemann organizer during early gastrulation. Unlike Frizzled proteins, endogenous Frzb was soluble. Frzb was secret able and could act across cell boundaries. In several functional assay s, Frzb antagonized Xwnt-8, a proposed ventralizing factor with an exp ression pattern complementary to that of Frzb. Furthermore, Frzb block ed induction of MyoD, an action reported recently for a dominant-negat ive Xwnt-8. Frzb coimmunoprecipitated with Wnt proteins, providing dir ect biochemical evidence for Frzb-Wnt interactions. These observations implicate Frzb in axial patterning and support the concept that Frzb binds and inactivates Xwnt-8 during gastrulation, preventing inappropr iate ventral signaling in developing dorsal tissues.