Gene Symbol: Frzb
Description: frizzled-related protein
Alias: Frp, Sfrp3, frezzled, fritz, frzb-1, secreted frizzled-related protein 3, frizzled-related protein 1, secreted frizzled-related sequence protein 3
Species: mouse
Products:     Frzb

Top Publications

  1. Lodewyckx L, Cailotto F, Thysen S, Luyten F, Lories R. Tight regulation of wingless-type signaling in the articular cartilage - subchondral bone biomechanical unit: transcriptomics in Frzb-knockout mice. Arthritis Res Ther. 2012;14:R16 pubmed publisher
    ..the articular cartilage and subchondral bone of the tibial plateau from mice deficient in frizzled-related protein (Frzb) compared to wild-type mice by transcriptome analysis...
  2. Lories R, Peeters J, Bakker A, Tylzanowski P, Derese I, Schrooten J, et al. Articular cartilage and biomechanical properties of the long bones in Frzb-knockout mice. Arthritis Rheum. 2007;56:4095-103 pubmed
    ..In particular, polymorphisms in the FRZB gene, a secreted WNT antagonist, have been associated with osteoarthritis...
  3. Sun J, Bonaguidi M, Jun H, Guo J, Sun G, Will B, et al. A septo-temporal molecular gradient of sfrp3 in the dentate gyrus differentially regulates quiescent adult hippocampal neural stem cell activation. Mol Brain. 2015;8:52 pubmed publisher mouse dentate gyrus resulting from the activity-regulated expression of secreted frizzled-related protein 3 (sfrp3) by mature neurons, which suppresses activation of radial glia-like neural stem cells (RGLs) through inhibition of ..
  4. Lickert H, Cox B, Wehrle C, Taketo M, Kemler R, Rossant J. Dissecting Wnt/beta-catenin signaling during gastrulation using RNA interference in mouse embryos. Development. 2005;132:2599-609 pubmed
    ..This functional genomic approach allows the rapid identification of functionally important components of embryonic development from large datasets of putative targets. ..
  5. Shimogori T, VanSant J, Paik E, Grove E. Members of the Wnt, Fz, and Frp gene families expressed in postnatal mouse cerebral cortex. J Comp Neurol. 2004;473:496-510 pubmed
    ..Thus, canonical Wnt signaling could be utilized in a major cortical input by Fz- and Lef1-expressing thalamic cells that innervate the Wnt-expressing cortex. ..
  6. Tebar M, Destree O, de Vree W, Ten Have Opbroek A. Expression of Tcf/Lef and sFrp and localization of beta-catenin in the developing mouse lung. Mech Dev. 2001;109:437-40 pubmed
    ..5 onward), and adjacent mesenchyme. Tcf1, Lef1, Tcf3, Tcf4, sFrp1, sFrp2 and sFrp4 were also expressed in the PE, AE, and adjacent mesenchyme in specific spatio-temporal patterns. ..
  7. Dawe C, Kooistra M, Fairbridge N, Pisio A, McDermid H. Role of chromatin remodeling gene Cecr2 in neurulation and inner ear development. Dev Dyn. 2011;240:372-83 pubmed publisher
    ..The mechanism of Cecr2 action in neurogenesis and inner ear development is likely complex. ..
  8. He F, Xiong W, Wang Y, Li L, Liu C, Yamagami T, et al. Epithelial Wnt/?-catenin signaling regulates palatal shelf fusion through regulation of Tgf?3 expression. Dev Biol. 2011;350:511-9 pubmed publisher
    ..Collectively, our results demonstrate an essential role for Wnt/?-catenin signaling in the epithelial component at the step of palate fusion during palate development by controlling the expression of Tgf?3 in the MEE. ..
  9. Alfieri C, Cheek J, Chakraborty S, Yutzey K. Wnt signaling in heart valve development and osteogenic gene induction. Dev Biol. 2010;338:127-35 pubmed publisher
    ..Together, these studies provide evidence for Wnt signaling as a regulator of endocardial cushion maturation as well as valve leaflet stratification, homeostasis, and pathogenesis. ..

More Information


  1. Kwon H, Lee H, Ji Y, Rubin J, Tomarev S. Myocilin is a modulator of Wnt signaling. Mol Cell Biol. 2009;29:2139-54 pubmed publisher
    ..against myocilin, as well as secreted inhibitors of Wnt signaling, secreted Frizzled-related protein 1 (sFRP1) or sFRP3, and beta-catenin small interfering RNA...
  2. Qian D, Jones C, Rzadzinska A, Mark S, Zhang X, Steel K, et al. Wnt5a functions in planar cell polarity regulation in mice. Dev Biol. 2007;306:121-33 pubmed
    ..that Wnt5a forms a reciprocal expression pattern with a Wnt antagonist, the secreted frizzled-related protein 3 (Sfrp3 or Frzb), along the axis of planar polarization in the cochlear epithelium...
  3. Kelly R, Jerome Majewska L, Papaioannou V. The del22q11.2 candidate gene Tbx1 regulates branchiomeric myogenesis. Hum Mol Genet. 2004;13:2829-40 pubmed
    ..While no abnormalities in branchiomeric myogenesis were detected in Tbx1(+/-) mice, reduced TBX1 levels may contribute to pharyngeal hypotonia in del22q11.2 patients...
  4. John A, Brylka H, Wiegreffe C, Simon R, Liu P, Jüttner R, et al. Bcl11a is required for neuronal morphogenesis and sensory circuit formation in dorsal spinal cord development. Development. 2012;139:1831-41 pubmed publisher
    ..of Bcl11a mutants and identified dysregulated expression of the gene encoding secreted frizzled-related protein 3 (sFRP3, or Frzb)...
  5. Jang M, Bonaguidi M, Kitabatake Y, Sun J, Song J, Kang E, et al. Secreted frizzled-related protein 3 regulates activity-dependent adult hippocampal neurogenesis. Cell Stem Cell. 2013;12:215-23 pubmed publisher
    ..Here, we report that neuronal activity decreases the expression of secreted frizzled-related protein 3 (sFRP3), a naturally secreted Wnt inhibitor highly expressed by adult dentate gyrus granule neurons...
  6. Peichel C, Kozak C, Luyten F, Vogt T. Evaluation of mouse Sfrp3/Frzb1 as a candidate for the lst, Ul, and Far mutants on chromosome 2. Mamm Genome. 1998;9:385-7 pubmed
  7. Lee C, Buttitta L, May N, Kispert A, Fan C. SHH-N upregulates Sfrp2 to mediate its competitive interaction with WNT1 and WNT4 in the somitic mesoderm. Development. 2000;127:109-18 pubmed
    ..Together, our results support the model that SHH-N at least in part employs SFRP2 to reduce WNT1/4 activity in the somitic mesoderm. ..
  8. Leyns L, Bouwmeester T, Kim S, Piccolo S, De Robertis E. Frzb-1 is a secreted antagonist of Wnt signaling expressed in the Spemann organizer. Cell. 1997;88:747-56 pubmed
    b>Frzb-1 is a secreted protein containing a domain similar to the putative Wnt-binding region of the frizzled family of transmembrane receptors. Frzb-1 is widely expressed in adult mammalian tissues...
  9. Yam J, Chan K, Wong V, Hsiao W. Transcriptional activity of the promoter region of rat frizzled-related protein gene. Biochem Biophys Res Commun. 2001;286:94-100 pubmed
    Frizzled-related protein (Frp) is a new family of secreted proteins involved in tumorigenesis and Wnt-signaling pathway...
  10. Mukhopadhyay M, Teufel A, Yamashita T, Agulnick A, Chen L, Downs K, et al. Functional ablation of the mouse Ldb1 gene results in severe patterning defects during gastrulation. Development. 2003;130:495-505 pubmed
    ..The expression of several Wnt inhibitors is curtailed in the mutant, suggesting that Wnt pathways may be involved in axial patterning regulated by Ldb1. ..
  11. Dann C, Hsieh J, Rattner A, Sharma D, Nathans J, Leahy D. Insights into Wnt binding and signalling from the structures of two Frizzled cysteine-rich domains. Nature. 2001;412:86-90 pubmed
    ..This work provides a framework for studies of homologous CRDs in proteins including muscle-specific kinase and Smoothened, a component of the Hedgehog signalling pathway. ..
  12. Hoang B, Thomas J, Abdul Karim F, Correia K, Conlon R, Luyten F, et al. Expression pattern of two Frizzled-related genes, Frzb-1 and Sfrp-1, during mouse embryogenesis suggests a role for modulating action of Wnt family members. Dev Dyn. 1998;212:364-72 pubmed
    ..We previously identified Frzb-1, a gene which encodes a secreted protein with homology in the ligand binding domain to the Wnt receptor Frizzled, ..
  13. Kurosaka H, Iulianella A, Williams T, Trainor P. Disrupting hedgehog and WNT signaling interactions promotes cleft lip pathogenesis. J Clin Invest. 2014;124:1660-71 pubmed publisher
  14. Vanyai H, Thomas T, Voss A. Mesodermal expression of Moz is necessary for cardiac septum development. Dev Biol. 2015;403:22-9 pubmed publisher
    ..Together, our data suggest that the molecular pathogenesis of VSDs in Moz germline mutant mice is due to loss of MOZ-dependant activation of mesodermal Tbx1 and Tbx5 expression. ..
  15. Shou S, Scott V, Reed C, Hitzemann R, Stadler H. Transcriptome analysis of the murine forelimb and hindlimb autopod. Dev Dyn. 2005;234:74-89 pubmed
    ..05) were detected between forelimb and hindlimb tissues including 38 new transcripts such as Rdh10, Frzb, Tbx18, and Hip that exhibit differential limb expression...
  16. Sarkar L, Sharpe P. Expression of Wnt signalling pathway genes during tooth development. Mech Dev. 1999;85:197-200 pubmed
    ..Wnt-5a and MFrzb1 show strong expression in the dental papilla mesenchyme. ..
  17. Geng R, Noda T, Mulvaney J, Lin V, Edge A, Dabdoub A. Comprehensive Expression of Wnt Signaling Pathway Genes during Development and Maturation of the Mouse Cochlea. PLoS ONE. 2016;11:e0148339 pubmed publisher
    ..The data revealed several potential key regulators for further study. ..
  18. Van Handel B, Montel Hagen A, Sasidharan R, Nakano H, Ferrari R, Boogerd C, et al. Scl represses cardiomyogenesis in prospective hemogenic endothelium and endocardium. Cell. 2012;150:590-605 pubmed publisher
    ..These results reveal unexpected plasticity in embryonic endothelium such that loss of a single master regulator can induce ectopic cardiomyogenesis from endothelial cells. ..
  19. Borello U, Coletta M, Tajbakhsh S, Leyns L, De Robertis E, Buckingham M, et al. Transplacental delivery of the Wnt antagonist Frzb1 inhibits development of caudal paraxial mesoderm and skeletal myogenesis in mouse embryos. Development. 1999;126:4247-55 pubmed
    ..Taken together, these results suggest that Wnt signals may act by regulating both myogenic commitment and expansion of committed cells in the mouse mesoderm. ..
  20. Bougault C, Priam S, Houard X, Pigenet A, Sudre L, Lories R, et al. Protective role of frizzled-related protein B on matrix metalloproteinase induction in mouse chondrocytes. Arthritis Res Ther. 2014;16:R137 pubmed publisher
    Our objective was to investigate whether a lack of frizzled-related protein B (FrzB), an extracellular antagonist of the Wnt signaling pathways, could enhance cartilage degradation by facilitating the expression, release and activation of ..
  21. Ladher R, Church V, Allen S, Robson L, Abdelfattah A, Brown N, et al. Cloning and expression of the Wnt antagonists Sfrp-2 and Frzb during chick development. Dev Biol. 2000;218:183-98 pubmed
    ..In this paper we report the expression patterns of the chick homologues of Frzb, a known Wnt antagonist, and Sfrp-2...
  22. Kim A, Lowenstein D, Pleasure S. Wnt receptors and Wnt inhibitors are expressed in gradients in the developing telencephalon. Mech Dev. 2001;103:167-72 pubmed
    ..In addition, SFRP-1 and SFRP-3 are expressed in opposing anterolateral to caudomedial gradients within the telencephalic ventricular zone throughout corticogenesis. ..
  23. Dreyer S, Naruse T, Morello R, Zabel B, Winterpacht A, Johnson R, et al. Lmx1b expression during joint and tendon formation: localization and evaluation of potential downstream targets. Gene Expr Patterns. 2004;4:397-405 pubmed developing joints and associated tissues in normal and Lmx1b knockout (KO) mice including: Gdf-5, sFrp2, sFrp3, Six1 and Six2. Lmx1b was diffusely expressed in the undifferentiated dorsal mesoderm of the emerging limb bud (E9...
  24. Lüdtke T, Rudat C, Wojahn I, Weiss A, Kleppa M, Kurz J, et al. Tbx2 and Tbx3 Act Downstream of Shh to Maintain Canonical Wnt Signaling during Branching Morphogenesis of the Murine Lung. Dev Cell. 2016;39:239-253 pubmed publisher maintain pro-proliferative mesenchymal Wnt signaling, in part by direct repression of the Wnt antagonists Frzb and Shisa3...
  25. Mayr T, Deutsch U, Kuhl M, Drexler H, Lottspeich F, Deutzmann R, et al. Fritz: a secreted frizzled-related protein that inhibits Wnt activity. Mech Dev. 1997;63:109-25 pubmed
    ..Here we describe the cloning and characterization of Fritz, a mouse (mfiz) and human (hfiz) gene which codes for a secreted protein that is structurally related to the ..
  26. van de Ven C, Bialecka M, Neijts R, Young T, Rowland J, Stringer E, et al. Concerted involvement of Cdx/Hox genes and Wnt signaling in morphogenesis of the caudal neural tube and cloacal derivatives from the posterior growth zone. Development. 2011;138:3451-62 pubmed publisher
    ..They shed a new light on the etiology of the caudal dysplasia or caudal regression range of human congenital defects. ..
  27. Cho S, Her S, Sun H, Choi O, Yang J, Kim S, et al. Differential effects of secreted frizzled-related proteins (sFRPs) on osteoblastic differentiation of mouse mesenchymal cells and apoptosis of osteoblasts. Biochem Biophys Res Commun. 2008;367:399-405 pubmed publisher
    ..In conclusion, we found that different repertoires of sFRPs exert differential effects on osteoblastic differentiation of mouse mesenchymal cells and cellular apoptosis of mouse osteoblasts in vitro. ..
  28. Wawrzak D, Metioui M, Willems E, Hendrickx M, De Genst E, Leyns L. Wnt3a binds to several sFRPs in the nanomolar range. Biochem Biophys Res Commun. 2007;357:1119-23 pubmed
    ..Here we show, using surface plasmon resonance and purified proteins, that sFRP1, sFRP2, sFRP4, and Frzb bind directly to Wnt3a with affinities in the nanomolar range...
  29. Chung Y, Baylink D, Srivastava A, Amaar Y, Tapia B, Kasukawa Y, et al. Effects of secreted frizzled-related protein 3 on osteoblasts in vitro. J Bone Miner Res. 2004;19:1395-402 pubmed
    To examine if sFRP3s act as decoy receptors for Wnt, we examined the effects of recombinant sFRP3 on mouse osteoblast proliferation and differentiation...
  30. Bennett C, Ross S, Longo K, Bajnok L, Hemati N, Johnson K, et al. Regulation of Wnt signaling during adipogenesis. J Biol Chem. 2002;277:30998-1004 pubmed
    ..Finally, we demonstrate that disruption of extracellular Wnt signaling by expression of secreted Frizzled related proteins causes spontaneous adipocyte conversion. ..
  31. Lescher B, Haenig B, Kispert A. sFRP-2 is a target of the Wnt-4 signaling pathway in the developing metanephric kidney. Dev Dyn. 1998;213:440-51 pubmed
  32. Thysen S, Cailotto F, Lories R. Osteogenesis induced by frizzled-related protein (FRZB) is linked to the netrin-like domain. Lab Invest. 2016;96:570-80 pubmed publisher
    ..Frizzled-related protein (FRZB, also known as secreted frizzled-related protein-3 (SFRP3)) is a Wnt modulator that contains an amino-terminal cysteine-rich domain (CRD) and a carboxy-terminal Netrin-like ..
  33. Askevold E, Aukrust P, Nymo S, Lunde I, Kaasbøll O, Aakhus S, et al. The cardiokine secreted Frizzled-related protein 3, a modulator of Wnt signalling, in clinical and experimental heart failure. J Intern Med. 2014;275:621-30 pubmed publisher
    ..We hypothesized that secreted frizzled-related protein 3 (sFRP3), a modulator of Wnt signalling, is related to the progression of HF...
  34. Zheng D, Bu Y, Wang L, Liu J. MicroRNA-130b Promotes Wear Particle-Induced Osteolysis via Downregulating Frizzled-Related Protein (FRZB). Curr Neurovasc Res. 2017;14:32-38 pubmed publisher
    ..and western blotting were performed to determine the expression levels of miR-130b and frizzled-related protein (FRZB), one potential target of miR-130b...
  35. Jang M, Kitabatake Y, Kang E, Jun H, Pletnikov M, Christian K, et al. Secreted frizzled-related protein 3 (sFRP3) regulates antidepressant responses in mice and humans. Mol Psychiatry. 2013;18:957-8 pubmed publisher
  36. Keil K, Mehta V, Branam A, Abler L, Buresh Stiemke R, Joshi P, et al. Wnt inhibitory factor 1 (Wif1) is regulated by androgens and enhances androgen-dependent prostate development. Endocrinology. 2012;153:6091-103 pubmed publisher
  37. Kele J, Andersson E, Villaescusa J, Cajanek L, Parish C, Bonilla S, et al. SFRP1 and SFRP2 dose-dependently regulate midbrain dopamine neuron development in vivo and in embryonic stem cells. Stem Cells. 2012;30:865-75 pubmed publisher
    ..Moreover, we suggest that low-medium concentrations of sFRPs may be used to enhance the DA differentiation of ESCs and improve their therapeutic application. ..
  38. Noda T, Oki S, Kitajima K, Harada T, Komune S, Meno C. Restriction of Wnt signaling in the dorsal otocyst determines semicircular canal formation in the mouse embryo. Dev Biol. 2012;362:83-93 pubmed publisher
    ..Our stage-specific functional analysis suggests that strict regulation of canonical Wnt signaling in the dorsal otocyst orchestrates the process of semicircular canal formation...
  39. Liu W, Li L, Li G, Garritano F, Shanske A, Frenz D. Coordinated molecular control of otic capsule differentiation: functional role of Wnt5a signaling and opposition by sfrp3 activity. Growth Factors. 2008;26:343-54 pubmed publisher
    ..We show that in the presence of secreted frizzled related protein 3 (sfrp3), a Wnt antagonist expressed in the developing inner ear, or Wnt5a-specific antisense ..
  40. Jones B, Beard J, Gibson J, Unger E, Allen R, McCarthy K, et al. Systems genetic analysis of peripheral iron parameters in the mouse. Am J Physiol Regul Integr Comp Physiol. 2007;293:R116-24 pubmed
    ..The results show that iron homeostasis is a complex trait and is influenced by multiple genes. ..
  41. Tylzanowski P, Bossuyt W, Thomas J, Luyten F. Characterization of Frzb-Cre transgenic mouse. Genesis. 2004;40:200-4 pubmed secreted antagonists that either bind to the receptors directly (Dkk1) or to Wnt molecules themselves (Sfrp-FRZB family), preventing its subsequent binding to the receptor...
  42. Liu H, Mohamed O, Dufort D, Wallace V. Characterization of Wnt signaling components and activation of the Wnt canonical pathway in the murine retina. Dev Dyn. 2003;227:323-34 pubmed
  43. Wodarz A, Nusse R. Mechanisms of Wnt signaling in development. Annu Rev Cell Dev Biol. 1998;14:59-88 pubmed
    ..Here we review recent data that have started to unravel the mechanisms of Wnt signaling. ..