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Frzb, a Secreted Protein Expressed in the Spemann Organizer, Binds and Inhibits Wnt-8
Open accessAbstract
We isolated a Xenopus homolog of Frzb, a newly described protein containing an amino-terminal Frizzled motif. It dorsalized Xenopus embryos and was expressed in the Spemann organizer during early gastrulation. Unlike Frizzled proteins, endogenous Frzb was soluble. Frzb was secretable and could act across cell boundaries. In several functional assays, Frzb antagonized Xwnt-8, a proposed ventralizing factor with an expression pattern complementary to that of Frzb. Furthermore, Frzb blocked induction of MyoD, an action reported recently for a dominant-negative Xwnt-8. Frzb coimmunoprecipitated with Wnt proteins, providing direct biochemical evidence for Frzb-Wnt interactions. These observations implicate Frzb in axial patterning and support the concept that Frzb binds and inactivates Xwnt-8 during gastrulation, preventing inappropriate ventral signaling in developing dorsal tissues.
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“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 [20]
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Cited by
Sorted by citations
The Wnt Signaling Pathway in Development and Disease
Logan, C. Y., & Nusse, R. (2004) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.20.010403.113126 · Cited by 5,325
“In general, both SFRPs and WIFs are thought to function as extracellular Wnt inhibitors (Bafico et al. 1999, Dennis et al. 1999, Hsieh et al. 1999a, Leyns et al. 1997, Salic et al. 1997, Uren et al. 2000, Wang et al. 1997).”
BackgroundPolakis, P. (2000) · Genes & Development · doi:10.1101/gad.14.15.1837 · Cited by 3,183
“The so-called secreted frizzled-related proteins (sFRP) bind to the wnt ligands, thereby exerting antagonistic activity when overexpressed in wnt signaling assays (Leyns et al. 1997; Wang et al. 1997).”
BackgroundWnt signaling: a common theme in animal development
Cadigan, K. M., & Nusse, R. (1997) · Genes & Development · doi:10.1101/gad.11.24.3286 · Cited by 2,567
“tein does not uniquely bind to cells expressing Dfz2; a variety of other Fz family members (Wang et al. 1996; Y.K. Wang et al. 1997), including the original Fz, also enable cells to interact with Wg (Table 3; Bhanot et al. 1996).”
BackgroundMECHANISMS OF WNT SIGNALING IN DEVELOPMENT
Wodarz, A., & Nusse, R. (1998) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.14.1.59 · Cited by 2,030
“…of Xwnt-5A to induce a secondary axis can be overcome by coinjection of human Frizzled 5, suggesting that the availability of a specific receptor rather than a fundamental difference in its signal transduction P1: APR/ary P2: ARS/dat QC: ARS/APM T1: ARS August 29, 1998 9:42 Annual Reviews AR066-03”
BackgroundDickkopf-1 is a member of a new family of secreted proteins and functions in head induction
Glinka, A., Wu, W., Delius, H., Monaghan, A. P., Blumenstock, C., & Niehrs, C. (1998) · Nature · doi:10.1038/34848 · Cited by 1,608
“Consistent with our two-inhibitor model for head formation, the organizer secretes at least one Wnt-antagonist, Frzb, which blocks muscle formation and anteriorizes embryo”
Method
Metadata
- Authors
- Wang, S., Krinks, M., Lin, K., Luyten, F. P., & Moos, M.
- Affiliations
- United States Food and Drug Administration (US)
- Center for Biologics Evaluation and Research (US)
- National Institutes of Health (US)
- Corresponding author
- Moos, Malcolm
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1997-03
- Volume
- 88
- Issue
- 6
- Pages
- 757-766
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1988350691
- Cited by
- 518
- References
- 70
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 8 · 2023: 9 · 2022: 11 · 2021: 6 · 2020: 12 · 2019: 3 · 2018: 13 · 2017: 17 · 2016: 6 · 2015: 12 · 2014: 15 · 2013: 9 · 2012: 14
- FWCI
- 17.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- George Washington University
- National Institutes of Health
- 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
- Health Sciences › Medicine › Oncology › Renal and related cancers
- Keywords
- FRZB, Spemann organizer, dorsalization, ventralization, gastrulation, axial patterning, MyoD, Wnt signaling inhibition, secreted proteins, Xenopus embryo
- MeSH terms
- Frizzled-Related Proteins, Animals, Biological Transport, Cell Communication, Dogs, Embryonic Induction, Female, Glycoproteins, Male, Mesoderm, Microsomes, Protein Binding, Proteins, Rabbits, RNA, Messenger, Solubility, Transcription, Genetic, Xenopus, Zygote, MyoD Protein, Gene Expression Regulation, Developmental, COS Cells, Zebrafish Proteins, Intracellular Signaling Peptides and Proteins, Wnt Proteins
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