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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Amino Acid Sequence
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Animals
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CHO Cells
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Carrier Proteins / genetics
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Carrier Proteins / isolation & purification
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Carrier Proteins / metabolism*
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Cricetinae
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Drosophila Proteins*
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Extracellular Matrix Proteins
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Humans
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Immunoglobulin G / genetics
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Immunoglobulin G / metabolism
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Intercellular Signaling Peptides and Proteins
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Intracellular Signaling Peptides and Proteins
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Mice
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Molecular Sequence Data
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Protein Binding
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Proto-Oncogene Proteins / antagonists & inhibitors
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Proto-Oncogene Proteins / metabolism*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Repressor Proteins*
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Sequence Homology, Amino Acid
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Signal Transduction
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Wnt Proteins
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Wnt1 Protein
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Xenopus
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Xenopus Proteins
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Zebrafish
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Zebrafish Proteins*
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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Drosophila Proteins
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Extracellular Matrix Proteins
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Immunoglobulin G
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Intercellular Signaling Peptides and Proteins
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Intracellular Signaling Peptides and Proteins
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Proto-Oncogene Proteins
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Recombinant Fusion Proteins
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Repressor Proteins
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WIF1 protein, human
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Wif1 protein, mouse
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Wnt Proteins
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Wnt1 Protein
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Xenopus Proteins
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Zebrafish Proteins
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wg protein, Drosophila
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wnt8a protein, Xenopus
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wnt8b protein, zebrafish
Associated data
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GENBANK/AF122922
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GENBANK/AF122923
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GENBANK/AF122924
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GENBANK/AF122925