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

• Published in: Nature (London) Vol. 398; no. 6726; pp. 431 - 436
• Main Authors: Hsieh, J C, Kodjabachian, L, Rebbert, M L, Rattner, A, Smallwood, P M, Samos, C H, Nusse, R, Dawid, I B, Nathans, J
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01-04-1999
• Subjects: Adaptor Proteins, Signal Transducing; Amino Acid Sequence; Animals; Carrier Proteins - genetics; Carrier Proteins - isolation & purification; Carrier Proteins - metabolism; Carrier Proteins - secretion; CHO Cells; Cricetinae; Drosophila; Drosophila Proteins; Extracellular Matrix Proteins; Freshwater; Genetics; Humans; Immunoglobulin G - genetics; Immunoglobulin G - metabolism; Intercellular Signaling Peptides and Proteins; Intracellular Signaling Peptides and Proteins; Mice; Molecular biology; Molecular Sequence Data; Molecules; Prenatal development; Protein Binding; Proteins; Proto-Oncogene Proteins - antagonists & inhibitors; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins - secretion; 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
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/18899

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.