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

Jen Chih Hsieh, Laurent Kodjabachian, Martha L. Rebbert, Amir Rattner, Philip M. Smallwood, Cynthia Harryman Samos, Roel Nusse, Igor B. Dawid, Jeremy Nathans

Research output: Contribution to journalArticlepeer-review

Abstract

The Wnt proteins constitute a large family of extracellular signalling molecules that are found throughout the animal kingdom and are important for a wide variety of normal and pathological developmental processes. 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, amphibia and mammals, and is expressed during Xenopus and zebrafish development in a complex pattern that includes paraxial presomitic mesoderm, notochord, branchial arches and neural crest derivatives. We use Xenopus embryos to show that WIF-1 overexpression affects somitogenesis (the generation of trunk mesoderm segments), in agreement with its normal expression in paraxial mesoderm. In vitro, WIF-1 binds to Drosophila Wingless and Xenopus Wnt8 produced by Drosophila S2 cells. Together with earlier results obtained with the secreted Frizzled-related proteins, our results indicate that Wnt proteins interact with structurally diverse extracellular inhibitors, presumably to fine-tune the spatial and temporal patterns of Wnt activity.

Original languageEnglish (US)
Pages (from-to)431-436
Number of pages6
JournalNature
Volume398
Issue number6726
DOIs
StatePublished - Apr 1 1999

ASJC Scopus subject areas

  • General

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