ZFIN ID: ZDB-PUB-990507-11
A new secreted protein that binds to Wnt proteins and inhibits their activities
Hsieh, J.C., Kodjabachian, L., Rebbert, M.L., Rattner, A., Smallwood, P.M., Samos, C.H., Nusse, R., Dawid, I.B., and Nathans, J.
Date: 1999
Source: Nature   398(6726): 431-436 (Journal)
Registered Authors: Dawid, Igor B., Kodjabachian, Laurent
Keywords: none
MeSH Terms:
  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • CHO Cells
  • Carrier Proteins/genetics
  • Carrier Proteins/isolation & purification
  • Carrier Proteins/metabolism*
  • Cricetinae
  • Drosophila Proteins*
  • Extracellular Matrix Proteins
  • Humans
  • Immunoglobulin G/genetics
  • Immunoglobulin G/metabolism
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins
  • Mice
  • Molecular Sequence Data
  • Protein Binding
  • Proto-Oncogene Proteins/antagonists & inhibitors
  • Proto-Oncogene Proteins/metabolism*
  • Recombinant Fusion Proteins/genetics
  • Recombinant Fusion Proteins/metabolism
  • Repressor Proteins*
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Wnt Proteins
  • Wnt1 Protein
  • Xenopus
  • Xenopus Proteins
  • Zebrafish
  • Zebrafish Proteins*
PubMed: 10201374 Full text @ Nature
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.