SIZZLED - A SECRETED XWNT8 ANTAGONIST EXPRESSED IN THE VENTRAL MARGINAL ZONE OF XENOPUS EMBRYOS

An expression cloning screen was used to isolate a novel gene homologo us to the extracellular cysteine-rich domain of frizzled receptors, Th e gene (which we called sizzled for secreted frizzled) was shown to en code a soluble secreted protein, containing a functional signal sequen ce but no transmembrane domains, Sizzled (szl) is capable of inhibitin g Xwnt8 as assayed by (1) dose-dependent inhibition of siamois inducti on by Xwnt8 in animal caps, (2) rescue of embryos ventralized by Xwnt8 DNA and (3) inhibition of XmyoD expression in the marginal zone, Szl can dorsalize Xenopus embryos if expressed after the midblastula trans ition, strengthening the idea that zygotic expression of wnts and in p articular of Xwnt8 plays a role in antagonizing dorsal signals. It als o suggests that inhibiting ventralizing wnts parallels the opposition of BMPs by noggin and chordin. szl expression is restricted to a narro w domain in the ventral marginal zone of gastrulating embryos. szl thu s encodes a secreted antagonist of wnt signaling likely involved in in hibiting Xwnt8 and XmyoD ventrally and whose restricted expression rep resents a new element in the molecular pattern of the ventral marginal zone.