Gene Symbol: Fzd4
Description: frizzled class receptor 4
Alias: Fz4, frizzled-4, frizzled homolog 4, fz-4, mFz4
Species: mouse
Products:     Fzd4

Top Publications

  1. Sheldahl L, Park M, Malbon C, Moon R. Protein kinase C is differentially stimulated by Wnt and Frizzled homologs in a G-protein-dependent manner. Curr Biol. 1999;9:695-8 pubmed
    ..Mfz7 and Mfz8 stimulated siamois and Xnr3 expression but not PKC activation, whereas Mfz3, Mfz4 and Mfz6 reciprocally stimulated PKC activation but not expression of siamois or Xnr3...
  2. Ye X, Wang Y, Rattner A, Nathans J. Genetic mosaic analysis reveals a major role for frizzled 4 and frizzled 8 in controlling ureteric growth in the developing kidney. Development. 2011;138:1161-72 pubmed publisher
    ..In cell culture, Fz4 and Fz8 can mediate noncanonical signaling stimulated by Wnt11, but only Fz4 mediates Wnt11-stimulated canonical ..
  3. Mikels A, Nusse R. Purified Wnt5a protein activates or inhibits beta-catenin-TCF signaling depending on receptor context. PLoS Biol. 2006;4:e115 pubmed
    ..function, Wnt5a can also activate beta-catenin signaling in the presence of the appropriate Frizzled receptor, Frizzled 4. Thus, this study shows for the first time that a single Wnt ligand can initiate discrete signaling pathways ..
  4. Xu Q, Wang Y, Dabdoub A, Smallwood P, Williams J, Woods C, et al. Vascular development in the retina and inner ear: control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair. Cell. 2004;116:883-95 pubmed
    ..One form of FEVR is caused by defects in Frizzled-4 (Fz4), a presumptive Wnt receptor...
  5. Chen Q, Zhang H, Liu Y, Adams S, Eilken H, Stehling M, et al. Endothelial cells are progenitors of cardiac pericytes and vascular smooth muscle cells. Nat Commun. 2016;7:12422 pubmed publisher
    ..Our findings identify a novel and unexpected population of progenitors for coronary mural cells with potential relevance for heart function and disease conditions. ..
  6. Fischer T, Guimera J, Wurst W, Prakash N. Distinct but redundant expression of the Frizzled Wnt receptor genes at signaling centers of the developing mouse brain. Neuroscience. 2007;147:693-711 pubmed
    ..This redundancy has to be taken into consideration for future analyses of Frizzled receptor function at these signaling centers in the mouse. ..
  7. D Agostino M, Crespi A, Polishchuk E, Generoso S, Martire G, Colombo S, et al. ER reorganization is remarkably induced in COS-7 cells accumulating transmembrane protein receptors not competent for export from the endoplasmic reticulum. J Membr Biol. 2014;247:1149-59 pubmed publisher
    ..question the conclusion that a dominant-negative mechanism would explain the dominance of the mutant L501fsX533 Fz4 allele in the transmission of a form of Familial exudative vitreoretinopathy...
  8. Ye X, Wang Y, Cahill H, Yu M, Badea T, Smallwood P, et al. Norrin, frizzled-4, and Lrp5 signaling in endothelial cells controls a genetic program for retinal vascularization. Cell. 2009;139:285-98 pubmed publisher
    ..Mutations in the Frizzled-4 (Fz4) receptor, Lrp5 coreceptor, or Norrin ligand cause retinal hypovascularization, but the mechanisms by which Norrin/..
  9. Fumoto K, Takigawa Imamura H, Sumiyama K, Kaneiwa T, Kikuchi A. Modulation of apical constriction by Wnt signaling is required for lung epithelial shape transition. Development. 2017;144:151-162 pubmed publisher

More Information


  1. Lobov I, Rao S, Carroll T, Vallance J, Ito M, Ondr J, et al. WNT7b mediates macrophage-induced programmed cell death in patterning of the vasculature. Nature. 2005;437:417-21 pubmed
    ..These findings indicate that macrophages can use WNT ligands to influence cell-fate decisions--including cell death--in adjacent cells, and raise the possibility that they do so in many different cellular contexts. ..
  2. Wang Y, Huso D, Cahill H, Ryugo D, Nathans J. Progressive cerebellar, auditory, and esophageal dysfunction caused by targeted disruption of the frizzled-4 gene. J Neurosci. 2001;21:4761-71 pubmed
    ..In this paper we report the phenotype of mice carrying a targeted deletion of the frizzled-4 (fz4) gene...
  3. Verani R, Cappuccio I, Spinsanti P, Gradini R, Caruso A, Magnotti M, et al. Expression of the Wnt inhibitor Dickkopf-1 is required for the induction of neural markers in mouse embryonic stem cells differentiating in response to retinoic acid. J Neurochem. 2007;100:242-50 pubmed
    ..These data suggest that induction of Dkk-1 and the ensuing inhibition of the canonical Wnt pathway is required for neural differentiation of ES cells. ..
  4. Dufourcq P, Leroux L, Ezan J, Descamps B, Lamazière J, Costet P, et al. Regulation of endothelial cell cytoskeletal reorganization by a secreted frizzled-related protein-1 and frizzled 4- and frizzled 7-dependent pathway: role in neovessel formation. Am J Pathol. 2008;172:37-49 pubmed
    ..Among the few Wnt family members implicated in vessel formation in adult, Wnt7b and Frizzled 4 have been shown as involved in vessel formation in the lung and in the retina, respectively...
  5. Kemp C, Willems E, Wawrzak D, Hendrickx M, Agbor Agbor T, Leyns L. Expression of Frizzled5, Frizzled7, and Frizzled10 during early mouse development and interactions with canonical Wnt signaling. Dev Dyn. 2007;236:2011-9 pubmed
  6. Junge H, Yang S, Burton J, Paes K, Shu X, French D, et al. TSPAN12 regulates retinal vascular development by promoting Norrin- but not Wnt-induced FZD4/beta-catenin signaling. Cell. 2009;139:299-311 pubmed publisher
    Mutations in the genes encoding the Wnt receptor Frizzled-4 (FZD4), coreceptor LRP5, or the ligand Norrin disrupt retinal vascular development and cause ophthalmic diseases...
  7. Omoto S, Hayashi T, Kitahara K, Takeuchi T, Ueoka Y. Autosomal dominant familial exudative vitreoretinopathy in two Japanese families with FZD4 mutations (H69Y and C181R). Ophthalmic Genet. 2004;25:81-90 pubmed
    ..to chromosome 11q13-23 (EVR1) locus, is caused by deletion mutations in the C- terminal region of the frizzled-4 (FZD4) gene...
  8. Zhou Y, Wang Y, TISCHFIELD M, Williams J, Smallwood P, Rattner A, et al. Canonical WNT signaling components in vascular development and barrier formation. J Clin Invest. 2014;124:3825-46 pubmed publisher
    ..Together, these data strongly support a model in which identical or nearly identical canonical WNT signaling mechanisms mediate neural tube and retinal vascularization and maintain the BBB and BRB. ..
  9. Descamps B, Sewduth R, Ferreira Tojais N, Jaspard B, Reynaud A, Sohet F, et al. Frizzled 4 regulates arterial network organization through noncanonical Wnt/planar cell polarity signaling. Circ Res. 2012;110:47-58 pubmed publisher
    ..We investigated the involvement of one of the receptors, Frizzled4 (Fzd4), in this process because its role has been implicated in retinal vascular development...
  10. Wang Y, Rattner A, Zhou Y, Williams J, Smallwood P, Nathans J. Norrin/Frizzled4 signaling in retinal vascular development and blood brain barrier plasticity. Cell. 2012;151:1332-44 pubmed publisher
    Norrin/Frizzled4 (Fz4) signaling activates the canonical Wnt pathway to control retinal vascular development...
  11. Avilés E, Pinto C, Hanna P, Ojeda J, Perez V, De Ferrari G, et al. Frizzled-9 impairs acetylcholine receptor clustering in skeletal muscle cells. Front Cell Neurosci. 2014;8:110 pubmed publisher
    ..Our findings represent the first evidence pointing to a crucial role of a Fzd-mediated, ?-catenin-dependent signaling on the assembly of the vertebrate NMJ. ..
  12. Yao R, Natsume Y, Noda T. MAGI-3 is involved in the regulation of the JNK signaling pathway as a scaffold protein for frizzled and Ltap. Oncogene. 2004;23:6023-30 pubmed
    ..These results indicate that MAGI-3 functions as a scaffold protein for frizzled-4 and Ltap and regulates the JNK signaling cascade. ..
  13. Bassett E, Tokarew N, Allemano E, Mazerolle C, Morin K, Mears A, et al. Norrin/Frizzled4 signalling in the preneoplastic niche blocks medulloblastoma initiation. elife. 2016;5: pubmed publisher
    ..We show that activation of the vascular regulatory signalling axis mediated by Norrin (an atypical Wnt)/Frizzled4 (Fzd4) inhibits MB initiation in the Ptch+/- mouse model...
  14. Kress E, Rezza A, Nadjar J, Samarut J, Plateroti M. The frizzled-related sFRP2 gene is a target of thyroid hormone receptor alpha1 and activates beta-catenin signaling in mouse intestine. J Biol Chem. 2009;284:1234-41 pubmed publisher
    ..Moreover, we describe in this study a novel mechanism of action of sFRP2, responsible for the activation of beta-catenin signaling. ..
  15. Lin S, Li B, Rao S, Yeo E, Hudson T, Nowlin B, et al. Macrophage Wnt7b is critical for kidney repair and regeneration. Proc Natl Acad Sci U S A. 2010;107:4194-9 pubmed publisher
  16. Xiao W, Liu W, Li Z, Liang D, Li L, White L, et al. Gene expression profiling in embryonic mouse lenses. Mol Vis. 2006;12:1692-8 pubmed
    ..Analysis of global gene expression profiles in embryonic mouse lenses has allowed us to identify several molecular pathways that are differentially regulated during early lens development. ..
  17. Borello U, Buffa V, Sonnino C, Melchionna R, Vivarelli E, Cossu G. Differential expression of the Wnt putative receptors Frizzled during mouse somitogenesis. Mech Dev. 1999;89:173-7 pubmed
    ..Frizzled 1, 3, 6, 7, 8, and 9 have specific expression in the forming and differentiating somites. The genes analyzed have a complex and partly overlapping pattern of expression in other regions of the embryo. ..
  18. Deutscher E, Hung Chang Yao H. Essential roles of mesenchyme-derived beta-catenin in mouse Müllerian duct morphogenesis. Dev Biol. 2007;307:227-36 pubmed
    ..In summary, our findings suggest that mesenchymal beta-catenin is a downstream effector of Wnt7a that mediates the patterning of the oviduct and proper differentiation of the uterus. ..
  19. Takada R, Hijikata H, Kondoh H, Takada S. Analysis of combinatorial effects of Wnts and Frizzleds on beta-catenin/armadillo stabilization and Dishevelled phosphorylation. Genes Cells. 2005;10:919-28 pubmed
  20. Ohta K, Ito A, Kuriyama S, Lupo G, Kosaka M, Ohnuma S, et al. Tsukushi functions as a Wnt signaling inhibitor by competing with Wnt2b for binding to transmembrane protein Frizzled4. Proc Natl Acad Sci U S A. 2011;108:14962-7 pubmed publisher
    ..protein Tsukushi (TSK) functions as a Wnt signaling inhibitor by binding directly to the cysteine-rich domain of Fzd4 with an affinity of 2.3 × 10(-10) M and competing with Wnt2b...
  21. Snowball J, Ambalavanan M, Cornett B, Lang R, Whitsett J, Sinner D. Mesenchymal Wnt signaling promotes formation of sternum and thoracic body wall. Dev Biol. 2015;401:264-75 pubmed publisher
    ..Thus, impaired Wls activity in the ventral body wall mesenchyme is a mechanism underlying ectopia cordis and unfused sternum. ..
  22. DeRossi C, Laiosa M, Silverstone A, Holdener B. Mouse fzd4 maps within a region of chromosome 7 important for thymus and cardiac development. Genesis. 2000;27:64-75 pubmed
    ..Using deletion mapping, we localized the Frizzled4 (Fzd4) gene to the jdf/thymus and cardiac development intervals.
  23. Yamada T, Akamatsu H, Hasegawa S, Inoue Y, Date Y, Mizutani H, et al. Melanocyte stem cells express receptors for canonical Wnt-signaling pathway on their surface. Biochem Biophys Res Commun. 2010;396:837-42 pubmed publisher
    ..Furthermore, FACS analysis showed that populations of Fzd4(+) cells and Fzd7(+) cells were different from those of Kit(+) cells (precursor of melanocytes: melanoblasts)...
  24. Bian W, Miao W, He S, Wan Z, Luo Z, Yu X. A novel Wnt5a-Frizzled4 signaling pathway mediates activity-independent dendrite morphogenesis via the distal PDZ motif of Frizzled 4. Dev Neurobiol. 2015;75:805-22 pubmed publisher
    ..Using primary hippocampal neuronal cultures as a model system, we report that Frizzled4 (Fzd4), a member of the Fzd family of Wnt receptors, specifically signals downstream of Wnt5a to promote dendrite ..
  25. He F, Xiong W, Yu X, Espinoza Lewis R, Liu C, Gu S, et al. Wnt5a regulates directional cell migration and cell proliferation via Ror2-mediated noncanonical pathway in mammalian palate development. Development. 2008;135:3871-9 pubmed publisher
    ..Our results reveal distinct regulatory roles for Wnt5a in gene expression and cell proliferation along the AP axis of the developing palate, and an essential role for Wnt5a in the regulation of directional cell migration...
  26. Kubo F, Takeichi M, Nakagawa S. Wnt2b controls retinal cell differentiation at the ciliary marginal zone. Development. 2003;130:587-98 pubmed
    ..b>Frizzled 4 and 5, seven-pass transmembrane Wnt receptors, were expressed in the peripheral and central part of the retina, ..
  27. 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. ..
  28. Austin T, Solar G, Ziegler F, Liem L, Matthews W. A role for the Wnt gene family in hematopoiesis: expansion of multilineage progenitor cells. Blood. 1997;89:3624-35 pubmed
    ..We conclude that WNTs stimulate the survival/proliferation of hematopoietic progenitors, demonstrating that WNTs comprise a novel class of hematopoietic cell regulators. ..
  29. Reddy S, Andl T, Lu M, Morrisey E, Millar S. Expression of Frizzled genes in developing and postnatal hair follicles. J Invest Dermatol. 2004;123:275-82 pubmed
  30. Hering H, Sheng M. Direct interaction of Frizzled-1, -2, -4, and -7 with PDZ domains of PSD-95. FEBS Lett. 2002;521:185-9 pubmed
  31. Donaldson I, Amin S, Hensman J, Kutejova E, Rattray M, Lawrence N, et al. Genome-wide occupancy links Hoxa2 to Wnt-?-catenin signaling in mouse embryonic development. Nucleic Acids Res. 2012;40:3990-4001 pubmed publisher
    ..The comprehensive mapping of Hoxa2-binding sites provides a framework to study Hox regulatory networks in vertebrate developmental processes. ..
  32. Ngo M, Borowska Fielding J, Heathcote G, Nejat S, Kelly M, McMaster C, et al. Fzd4 Haploinsufficiency Delays Retinal Revascularization in the Mouse Model of Oxygen Induced Retinopathy. PLoS ONE. 2016;11:e0158320 pubmed publisher
    Mutations in genes that code for components of the Norrin-FZD4 ligand-receptor complex cause the inherited childhood blinding disorder familial exudative vitreoretinopathy (FEVR)...
  33. Peissel B, Zaffaroni D, Pazzaglia S, Manenti G, Zanesi N, Zedda I, et al. Use of intercross outbred mice and single nucleotide polymorphisms to map skin cancer modifier loci. Mamm Genome. 2001;12:291-4 pubmed
    ..These results point to the important role of the Stks1 locus in mouse skin tumorigenesis in independent crosses. The shortened Skts1 mapping region should facilitate the identification of candidate genes. ..
  34. Rattner A, Wang Y, Zhou Y, Williams J, Nathans J. The role of the hypoxia response in shaping retinal vascular development in the absence of Norrin/Frizzled4 signaling. Invest Ophthalmol Vis Sci. 2014;55:8614-25 pubmed publisher
    ..Retinal vascular structure was analyzed in mice with mutation of Ndp (the gene coding for Norrin) or Frizzle4 (Fz4) with or without three additional perturbations: (1) retinal hyperoxia and reduction of VEGF, (2) reduced induction ..
  35. Paes K, Wang E, Henze K, Vogel P, Read R, Suwanichkul A, et al. Frizzled 4 is required for retinal angiogenesis and maintenance of the blood-retina barrier. Invest Ophthalmol Vis Sci. 2011;52:6452-61 pubmed publisher
    PURPOSE. Mice deficient in the secreted protein Norrin or its receptor Frizzled-4 (FZD4) exhibit incomplete vascularization of the neural retina...
  36. 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
  37. Zhou Y, Nathans J. Gpr124 controls CNS angiogenesis and blood-brain barrier integrity by promoting ligand-specific canonical wnt signaling. Dev Cell. 2014;31:248-56 pubmed publisher
    ..These experiments identify Gpr124 as a ligand-specific coactivator of canonical Wnt signaling. ..
  38. Lossie A, Nakamura H, Thomas S, Justice M. Mutation of l7Rn3 shows that Odz4 is required for mouse gastrulation. Genetics. 2005;169:285-99 pubmed
    ..Together, our data indicate that Odz4 is mutated in the l7Rn3 allele series and performs roles in the mouse brain, heart, and embryonic patterning similar to those of its Drosophila counterpart. ..
  39. Hsieh M, Boerboom D, Shimada M, Lo Y, Parlow A, Luhmann U, et al. Mice null for Frizzled4 (Fzd4-/-) are infertile and exhibit impaired corpora lutea formation and function. Biol Reprod. 2005;73:1135-46 pubmed
    ..transcripts encoding specific Wnt ligands and Frizzled receptors including Wnt4, Frizzled1 (Fzd1), and Frizzled4 (Fzd4) were expressed in a cell-specific manner in the adult mouse ovary...
  40. Wang Z, Shu W, Lu M, Morrisey E. Wnt7b activates canonical signaling in epithelial and vascular smooth muscle cells through interactions with Fzd1, Fzd10, and LRP5. Mol Cell Biol. 2005;25:5022-30 pubmed
    ..Together, these data demonstrate that Wnt7b signals through Fzd1 and -10 and LRP5 and implicate these Wnt coreceptors in the regulation of lung airway and vascular development. ..
  41. Li Y, Liu J, McLaughlin N, Bachvarov D, Saifudeen Z, El Dahr S. Genome-wide analysis of the p53 gene regulatory network in the developing mouse kidney. Physiol Genomics. 2013;45:948-64 pubmed publisher
    ..We conclude p53 targets transcriptional networks regulating nephrogenesis and cellular metabolism during kidney development. ..
  42. Mukai A, Yamamoto Hino M, Awano W, Watanabe W, Komada M, Goto S. Balanced ubiquitylation and deubiquitylation of Frizzled regulate cellular responsiveness to Wg/Wnt. EMBO J. 2010;29:2114-25 pubmed publisher
    ..These results unveil a novel mechanism that regulates the cellular responsiveness to Wg/Wnt by controlling the cell surface level of Frizzled. ..
  43. Markovič R, Peltan J, Gosak M, Horvat D, Zalik B, Séguy B, et al. Planar cell polarity genes frizzled4 and frizzled6 exert patterning influence on arterial vessel morphogenesis. PLoS ONE. 2017;12:e0171033 pubmed publisher
    ..Experiments were performed on frizzled4 (Fzd4-/-) and frizzled6 (Fzd6-/-) deleted mice and littermate controls (WT) perfused with a contrast medium after ..
  44. Bryja V, Cajanek L, Grahn A, Schulte G. Inhibition of endocytosis blocks Wnt signalling to beta-catenin by promoting dishevelled degradation. Acta Physiol (Oxf). 2007;190:55-61 pubmed
  45. Chen J, Stahl A, Krah N, Seaward M, Dennison R, Sapieha P, et al. Wnt signaling mediates pathological vascular growth in proliferative retinopathy. Circulation. 2011;124:1871-81 pubmed publisher
    ..These results demonstrate an important role of Wnt signaling in pathological vascular development in retinopathy and show a novel function of Cln5 in promoting angiogenesis. ..