A new secreted protein that binds to Wnt proteins and inhibits their activites
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.
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A number of secreted proteins that bind to Wnts and prevent their interaction with either Fz or LRP5/6 to antagonize Wnt signaling have been identified, including Dickkopf (Dkk) proteins, Wnt-inhibitor protein (WIF), soluble Frizzled-related proteins (SFRP), Cerebrus, Frzb and Wise.
“In the extra-cellular matrix, a number of secreted proteins that bind to Wnts and prevent their interaction with either Fz or LRP5/6 to antagonize Wnt signaling have been identified. These include Dickkopf (Dkk) proteins,16 Wnt-inhibitor protein (WIF),17 soluble Frizzled-related proteins (SFRP),18 Cerebrus,19 Frzb20 and the context dependent Wnt inhibitor Wise.21”
From Wnt signal transduction pathways (2008) · cites this paper as [17]
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- Authors
- Hsieh, J.-C., Kodjabachian, L., Rebbert, M. L., Rattner, A., Smallwood, P. M., Samos, C. H., Nusse, R., Dawid, I. B., & Nathans, J.
- Affiliations
- Howard Hughes Medical Institute (US)
- National Institutes of Health (US)
- Corresponding author
- Nathans, Jeremy
- Venue
- Nature
- Published
- 1999-04
- Volume
- 398
- Issue
- 6726
- Pages
- 431-436
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1631692643
- Cited by
- 750
- References
- 18
- Citations by year
- 2026: 13 · 2025: 9 · 2024: 18 · 2023: 22 · 2022: 19 · 2021: 48 · 2020: 32 · 2019: 22 · 2018: 31 · 2017: 35 · 2016: 19 · 2015: 28 · 2014: 33 · 2013: 32 · 2012: 37
- FWCI
- 8.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Keywords
- WIF1, Wnt signaling, Wnt8, wingless, FRZB, somitogenesis, paraxial mesoderm, notochord, neural crest, developmental gene expression, Xenopus embryo, zebrafish development
- MeSH terms
- Amino Acid Sequence, Animals, Carrier Proteins, Cricetinae, Humans, Immunoglobulin G, Molecular Sequence Data, Protein Binding, Proto-Oncogene Proteins, Recombinant Fusion Proteins, Repressor Proteins, Xenopus, Zebrafish, Signal Transduction, Extracellular Matrix Proteins, CHO Cells, Sequence Homology, Amino Acid, Drosophila Proteins, Xenopus Proteins, Zebrafish Proteins, Intercellular Signaling Peptides and Proteins, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Wnt Proteins, Wnt1 Protein, Mice
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