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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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 [20]
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“Frzb-1 is a secreted protein that contains a domain similar to the Wnt-binding region of the Frizzled Wnt receptors, and functions by binding to Wnts and antagonizing their activit”
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“or through overexpression of a Wnt-specific inhibitor, Frz”
Wnt Signalling in Mammalian Development and Cancer
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“The largest family of such proteins so far discovered are the secreted Frizzled-Related Proteins (sFRP) 1–5 [95–101].”
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“, 2008)] and Crescent (Cres) are thought to negatively regulate Wnt signalling to protect the head region from posteriorisation and CEMs by Wnts by opposite concentration gradients of sFRPs against Wnts (Leyns et al., 1997; Wang et al., 1997; Pera and De Robertis, 2000; Shibata et al., 2005).”
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“In addition, a loss of function polymorphism in the SFRP3 gene, encoding for a soluble Wnt inhibitor (Leyns et al., 1997; Wang et al., 1997), has been linked to an increased susceptibility to develop OA (Loughlin et al.”
BackgroundHead in the WNT: the molecular nature of Spemann’s head organizer
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“frzB and sizzled (szl), which encode secreted proteins that act as antagonists of XWnt-8 signaling, are expressed during gastrulation in dorsal and ventral mesodermal domains, respectively (Leyns et al., 1997; Salic et al., 1997; Wang et al., 1997).”
Connective-tissue growth factor modulates WNT signalling and interacts with the WNT receptor complex
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“On the other hand, multiple Wnt antagonists, such as Frzb/Sfrp3, Crescent, Shisa, and Dkk1, are expressed in the head region (Leyns et al. 1997; Wang et al. 1997; Glinka et al. 1998; Shibata et al. 2005; Yamamoto et al. 2005).”
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“FRP-3 binds to and inhibits secondary axisforming activity of Wnt-1 and Wnt-8 in Xenopus embryos [ 49 ], but blocks neither secondary axis activity ofWnt-5a nor downstream gene transcription in response to Wnt-3a or Wnt-11 [50].”
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BMP-2/-4 and Wnt-8 cooperatively pattern the Xenopus mesoderm
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“…mutations in the LRP5 or LRP6 resulting in truncated proteins lacking the extracellular domain, induced a constitutively active canonical WNT signal, whereas the lack of the intracellular domain results in dominant negative receptors (G. Liu et al., 2003; Tamai et al., 2000; Wehrli et al., 2000).”
Background5 Cellular Mechanisms of Wingless/Wnt Signal Transduction
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Anterior Endomesoderm Specification inXenopusby Wnt/β-catenin and TGF-β Signalling Pathways
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“However, this signaling pathway can be modulated by a recently identi®ed group of soluble proteins, the soluble Frizzled-related proteins (sFRPs; secreted apoptosis-related proteins, SARPs) (Wang et al., 1997; Leyns et al., 1997; Rattner et al., 1997; Finch et al., 1997; Melkonyan et al., 1997).”
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“Additionally, in the mouse, four secreted Frizzled-related proteins (sFRPs) have been cloned (Rattner et al., 1997), some of which have been shown to bind Wnts and antagonize Wnt-mediated signaling (Wang et al., 1997a,b; Rattner et al., 1997).”
Background
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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