Gene Symbol: Fzd6
Description: frizzled class receptor 6
Alias: Fz6, frizzled-6, frizzled homolog 6, fz-6, mFz6
Species: mouse
Products:     Fzd6

Top Publications

  1. Lyons J, Mueller U, Ji H, Everett C, Fang X, Hsieh J, et al. Wnt-4 activates the canonical beta-catenin-mediated Wnt pathway and binds Frizzled-6 CRD: functional implications of Wnt/beta-catenin activity in kidney epithelial cells. Exp Cell Res. 2004;298:369-87 pubmed
  2. Fröjmark A, Schuster J, Sobol M, Entesarian M, Kilander M, Gabrikova D, et al. Mutations in Frizzled 6 cause isolated autosomal-recessive nail dysplasia. Am J Hum Genet. 2011;88:852-860 pubmed publisher
    ..and DNA sequence analysis revealed homozygous nonsense and missense mutations in FZD(6), the gene encoding Frizzled 6. FZD(6) belongs to a family of highly conserved membrane-bound WNT receptors involved in developmental processes ..
  3. Devenport D, Fuchs E. Planar polarization in embryonic epidermis orchestrates global asymmetric morphogenesis of hair follicles. Nat Cell Biol. 2008;10:1257-68 pubmed publisher
    ..Hair follicle initiation coincides with asymmetric redistribution of Vangl2, Celsr1 and Fzd6 within the embryonic epidermal basal layer...
  4. Wang Y, Badea T, Nathans J. Order from disorder: Self-organization in mammalian hair patterning. Proc Natl Acad Sci U S A. 2006;103:19800-5 pubmed
    Hairs, feathers, and scales normally exhibit precise orientations with respect to the body axes. In Frizzled6 (Fz6)(-/-) mice, the global orientation of hair follicles is disrupted, leading to waves, whorls, and tufts, each comprising ..
  5. Wang Y, Guo N, Nathans J. The role of Frizzled3 and Frizzled6 in neural tube closure and in the planar polarity of inner-ear sensory hair cells. J Neurosci. 2006;26:2147-56 pubmed
    In the mouse, Frizzled3 (Fz3) and Frizzled6 (Fz6) have been shown previously to control axonal growth and guidance in the CNS and hair patterning in the skin, respectively...
  6. Wang Y, Chang H, Nathans J. When whorls collide: the development of hair patterns in frizzled 6 mutant mice. Development. 2010;137:4091-9 pubmed publisher
    Surface appendages such as bristles, feathers and hairs exhibit both long- and short-range order. In the frizzled 6 null (Fz6(-/-)) mouse the orientations of the earliest born hair follicles are uncorrelated, but over time the follicles ..
  7. Deans M, Antic D, Suyama K, Scott M, Axelrod J, Goodrich L. Asymmetric distribution of prickle-like 2 reveals an early underlying polarization of vestibular sensory epithelia in the inner ear. J Neurosci. 2007;27:3139-47 pubmed
    ..b>Frizzled 6 (Fz6), a second PCP protein, is distributed opposite Pk2 along the lateral side of vestibular support cells...
  8. Guo N, Hawkins C, Nathans J. Frizzled6 controls hair patterning in mice. Proc Natl Acad Sci U S A. 2004;101:9277-81 pubmed
    ..We show here that Frizzled6 (Fz6), one member of a large family of integral membrane Wnt receptors, controls macroscopic hair patterning in the ..
  9. Fukuda T, Kominami K, Wang S, Togashi H, Hirata K, Mizoguchi A, et al. Aberrant cochlear hair cell attachments caused by Nectin-3 deficiency result in hair bundle abnormalities. Development. 2014;141:399-409 pubmed publisher
    ..These results indicate that, owing to the loss of Nectin-3, hair cells contact each other inappropriately and form abnormal junctions, ultimately resulting in abnormal hair bundle orientation and morphology. ..

More Information


  1. Abidin B, Hammami A, Stager S, Heinonen K. Infection-adapted emergency hematopoiesis promotes visceral leishmaniasis. PLoS Pathog. 2017;13:e1006422 pubmed publisher
    ..Our results demonstrate that L. donovani is able to subvert host bone marrow emergency responses to facilitate parasite persistence, and put forward hematopoiesis as a novel therapeutic target in chronic infections. ..
  2. 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
  3. Stefater J, Lewkowich I, Rao S, Mariggi G, Carpenter A, Burr A, et al. Regulation of angiogenesis by a non-canonical Wnt-Flt1 pathway in myeloid cells. Nature. 2011;474:511-5 pubmed publisher
    ..These findings indicate that resident myeloid cells can use a non-canonical, Wnt-Flt1 pathway to suppress angiogenic branching. ..
  4. Chang H, Nathans J. Responses of hair follicle-associated structures to loss of planar cell polarity signaling. Proc Natl Acad Sci U S A. 2013;110:E908-17 pubmed publisher
    ..Previous work has implicated Frizzled6 (Fz6)-mediated planar cell polarity (PCP) signaling in the initial specification of hair follicle orientation...
  5. Cui C, Klar J, Georgii Heming P, Fröjmark A, Baig S, Schlessinger D, et al. Frizzled6 deficiency disrupts the differentiation process of nail development. J Invest Dermatol. 2013;133:1990-7 pubmed publisher
    ..of nail (and claw) development is largely unknown, but we have recently identified a Wnt receptor gene, Frizzled6 (Fzd6), that is mutated in a human autosomal-recessive nail dysplasia...
  6. Wu Q, Zierold C, Ranheim E. Dysregulation of Frizzled 6 is a critical component of B-cell leukemogenesis in a mouse model of chronic lymphocytic leukemia. Blood. 2009;113:3031-9 pubmed publisher
    ..We find that, in the course of leukemogenesis, the expression of Wnt16, Wnt10alpha, Fzd1, and most dramatically, Fzd6, is progressively up-regulated in the transformed CD5(+) B cells of these mice, as are beta-catenin protein levels...
  7. Vladar E, Bayly R, Sangoram A, Scott M, Axelrod J. Microtubules enable the planar cell polarity of airway cilia. Curr Biol. 2012;22:2203-12 pubmed publisher
  8. 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 euthanasia and exsanguination...
  9. Korstanje R, Desai J, Lazar G, King B, Rollins J, Spurr M, et al. Quantitative trait loci affecting phenotypic variation in the vacuolated lens mouse mutant, a multigenic mouse model of neural tube defects. Physiol Genomics. 2008;35:296-304 pubmed publisher
    ..candidate genes for these modifiers including two GPCRs that cause NTD or skin/pigmentation defects (Modvl4: Frizzled homolog 6; Modvl5: Melanocortin 5 receptor)...
  10. 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. ..
  11. 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. ..
  12. Yamamoto S, Nishimura O, Misaki K, Nishita M, Minami Y, Yonemura S, et al. Cthrc1 selectively activates the planar cell polarity pathway of Wnt signaling by stabilizing the Wnt-receptor complex. Dev Cell. 2008;15:23-36 pubmed publisher
    ..These results suggest that Cthrc1 is a Wnt cofactor protein that selectively activates the Wnt/PCP pathway by stabilizing ligand-receptor interaction. ..
  13. Liu M, Guan Z, Shen Q, Flinter F, Dominguez L, Ahn J, et al. Ulk4 Regulates Neural Stem Cell Pool. Stem Cells. 2016;34:2318-31 pubmed publisher
    ..ULK4, therefore, may significantly contribute to neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. Stem Cells 2016;34:2318-2331. ..
  14. Osmundsen H, Landin M, From S, Kolltveit K, Risnes S. Changes in gene-expression during development of the murine molar tooth germ. Arch Oral Biol. 2007;52:803-13 pubmed
    ..Such data is therefore useful in directing attention towards genes, or cellular activities, which likely are worthy of further studies as regards their involvement in odontogenesis...
  15. Hua Z, Chang H, Wang Y, Smallwood P, Nathans J. Partial interchangeability of Fz3 and Fz6 in tissue polarity signaling for epithelial orientation and axon growth and guidance. Development. 2014;141:3944-54 pubmed publisher
    ..determined the extent to which frizzled 3 (Fz3) can rescue the hair follicle and Merkel cell polarity defects in frizzled 6-null (Fz6(-/-)) mice, and, reciprocally, the extent to which Fz6 can rescue the axon growth and guidance defects ..
  16. 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
  17. Sarkar L, Sharpe P. Expression of Wnt signalling pathway genes during tooth development. Mech Dev. 1999;85:197-200 pubmed
    ..in situ hybridisation analysis of six Wnt genes Wnts-3, -4, -5a, -6, -7b, and 10b together with Wnt receptor MFz6 and receptor agonist/antagonists MFrzb1 and Mfrp2 during murine odontogenesis from the earliest formation of the ..
  18. Abidin B, Owusu Kwarteng E, Heinonen K. Frizzled-6 Regulates Hematopoietic Stem/Progenitor Cell Survival and Self-Renewal. J Immunol. 2015;195:2168-76 pubmed publisher
    ..In this study, we show that a noncanonical Wnt receptor, Frizzled-6 (Fzd6), regulates HSPC expansion and survival in a hematopoietic cell-intrinsic manner...
  19. Takagishi M, Sawada M, Ohata S, Asai N, Enomoto A, Takahashi K, et al. Daple Coordinates Planar Polarized Microtubule Dynamics in Ependymal Cells and Contributes to Hydrocephalus. Cell Rep. 2017;20:960-972 pubmed publisher
    ..These results demonstrate an important role for Daple in planar polarity in motile cilia and provide a framework for understanding the mechanisms and functions of planar polarization in the ependymal cells. ..
  20. 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. ..
  21. Stuebner S, Faus Kessler T, Fischer T, Wurst W, Prakash N. Fzd3 and Fzd6 deficiency results in a severe midbrain morphogenesis defect. Dev Dyn. 2010;239:246-60 pubmed publisher
    ..Fzd3 is expressed throughout the mouse anterior neural tube, whereas Fzd6 is restricted to the MHR...
  22. Steele B, Harper M, Macaulay I, Morrell C, Perez Tamayo A, Foy M, et al. Canonical Wnt signaling negatively regulates platelet function. Proc Natl Acad Sci U S A. 2009;106:19836-41 pubmed publisher
    ..Finally, disruption of the Wnt Frizzled 6 receptor in the mouse resulted in a hyperactivatory platelet phenotype and a reduced sensitivity to Wnt3a...
  23. Nishimura T, Honda H, Takeichi M. Planar cell polarity links axes of spatial dynamics in neural-tube closure. Cell. 2012;149:1084-97 pubmed publisher
    ..Together our findings demonstrate that PCP signals confer anisotropic contractility on the AJs, producing cellular forces that promote the polarized bending of the neural plate...
  24. Chang H, Cahill H, Smallwood P, Wang Y, Nathans J. Identification of Astrotactin2 as a Genetic Modifier That Regulates the Global Orientation of Mammalian Hair Follicles. PLoS Genet. 2015;11:e1005532 pubmed publisher
    ..In Frizzled6(-/-) (Fz6(-/-)) mice, hair follicle orientations on the head and back are nearly random at birth, but reorient during early ..
  25. Siletti K, Tarchini B, Hudspeth A. Daple coordinates organ-wide and cell-intrinsic polarity to pattern inner-ear hair bundles. Proc Natl Acad Sci U S A. 2017;114:E11170-E11179 pubmed publisher
    ..Our results suggest that the primary cilium or an associated structure influences the domain of cell-intrinsic signals that shape the hair bundle. Daple is therefore essential to orient and pattern sensory hair bundles. ..
  26. Tarchini B, Jolicoeur C, Cayouette M. A molecular blueprint at the apical surface establishes planar asymmetry in cochlear hair cells. Dev Cell. 2013;27:88-102 pubmed publisher
    ..G?i is additionally required for lateral orientation of cochlear hair cells, providing a possible mechanism to couple the emergence of asymmetric stereocilia bundles with planar cell polarity. ..
  27. Panousopoulou E, Hobbs C, Mason I, Green J, Formstone C. Epiboly generates the epidermal basal monolayer and spreads the nascent mammalian skin to enclose the embryonic body. J Cell Sci. 2016;129:1915-27 pubmed publisher
    ..We observe a failure of ventral enclosure in Crash mutants suggesting that defective epidermal spreading might underlie some ventral wall birth defects. ..
  28. Soshnikova N, Zechner D, Huelsken J, Mishina Y, Behringer R, Taketo M, et al. Genetic interaction between Wnt/beta-catenin and BMP receptor signaling during formation of the AER and the dorsal-ventral axis in the limb. Genes Dev. 2003;17:1963-8 pubmed
    ..Thus, AER formation and dorsal-ventral patterning of limbs are tightly controlled by an intricate interplay between Wnt/beta-catenin and BMP receptor signaling. ..
  29. 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. ..
  30. Lee J, Andreeva A, Sipe C, Liu L, Cheng A, Lu X. PTK7 regulates myosin II activity to orient planar polarity in the mammalian auditory epithelium. Curr Biol. 2012;22:956-66 pubmed publisher
    ..These findings suggest that PTK7 acts in conjunction with the noncanonical Wnt pathway to orient epithelial PCP through modulation of myosin II-based contractile tension between supporting cells and hair cells. ..
  31. Hoffman M, Kidder B, Steinberg Z, Lakhani S, Ho S, Kleinman H, et al. Gene expression profiles of mouse submandibular gland development: FGFR1 regulates branching morphogenesis in vitro through BMP- and FGF-dependent mechanisms. Development. 2002;129:5767-78 pubmed
    ..Taken together, our results suggest specific FGFs and BMPs play reciprocal roles in regulating branching morphogenesis and FGFR1 signaling plays a central role by regulating both FGF and BMP expression. ..
  32. Andl T, Reddy S, Gaddapara T, Millar S. WNT signals are required for the initiation of hair follicle development. Dev Cell. 2002;2:643-53 pubmed
    ..This phenotype indicates that activation of WNT signaling in the skin precedes, and is required for, localized expression of regulatory genes and initiation of hair follicle placode formation. ..
  33. Chang H, Smallwood P, Williams J, Nathans J. The spatio-temporal domains of Frizzled6 action in planar polarity control of hair follicle orientation. Dev Biol. 2016;409:181-193 pubmed publisher
    ..The present study uses conditional knockout alleles of the PCP genes Frizzled6 (Fz6), Vangl1, and Vangl2, together with a series of Cre drivers to interrogate the spatio-temporal domains of PCP gene ..
  34. van Helden Y, Godschalk R, Heil S, Bunschoten A, Hessel S, Amengual J, et al. Downregulation of Fzd6 and Cthrc1 and upregulation of olfactory receptors and protocadherins by dietary beta-carotene in lungs of Bcmo1-/- mice. Carcinogenesis. 2010;31:1329-37 pubmed publisher
    ..b>Frizzled homolog 6 (Fzd6) and collagen triple helix repeat containing 1 (Cthrc1) were significantly downregulated (fold changes ..
  35. 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. ..
  36. Piga R, van Dartel D, Bunschoten A, van der Stelt I, Keijer J. Role of Frizzled6 in the molecular mechanism of beta-carotene action in the lung. Toxicology. 2014;320:67-73 pubmed publisher
    ..genes particularly strongly down-regulated by BC in lung tissue of the male Bcmo1(-/-) mice: frizzled homologue 6 (Fzd6) and collagen triple helix repeat containing 1 (Cthrc1)...
  37. Krutzfeldt J, Rösch N, Hausser J, Manoharan M, Zavolan M, Stoffel M. MicroRNA-194 is a target of transcription factor 1 (Tcf1, HNF1?) in adult liver and controls expression of frizzled-6. Hepatology. 2012;55:98-107 pubmed publisher
    ..This approach revealed frizzled-6 (Fzd6) as a robust endogenous target of miR-194...
  38. 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. ..
  39. De Langhe S, Sala F, del Moral P, Fairbanks T, Yamada K, Warburton D, et al. Dickkopf-1 (DKK1) reveals that fibronectin is a major target of Wnt signaling in branching morphogenesis of the mouse embryonic lung. Dev Biol. 2005;277:316-31 pubmed
    ..DKK1-induced morphogenetic defects can be mimicked by inhibition of FN and overcome by addition of exogenous FN, suggesting an involvement of FN in Wnt-regulated morphogenetic processes. ..
  40. Copley C, Duncan J, Liu C, Cheng H, Deans M. Postnatal refinement of auditory hair cell planar polarity deficits occurs in the absence of Vangl2. J Neurosci. 2013;33:14001-16 pubmed publisher
    ..Together, these data demonstrate a Vangl2-independent refinement mechanism that actively reorients auditory stereociliary bundles and reveals an unexpected role of Vangl2 during supporting cell morphogenesis. ..
  41. Devenport D, Oristian D, Heller E, Fuchs E. Mitotic internalization of planar cell polarity proteins preserves tissue polarity. Nat Cell Biol. 2011;13:893-902 pubmed publisher
    ..A cytoplasmic dileucine motif governs mitotic internalization of atypical cadherin Celsr1, which recruits Vang2 and Fzd6 to endosomes...
  42. Heinonen K, Vanegas J, Lew D, Krosl J, Perreault C. Wnt4 enhances murine hematopoietic progenitor cell expansion through a planar cell polarity-like pathway. PLoS ONE. 2011;6:e19279 pubmed publisher
    ..Lastly, we identified Fz6 as a receptor for Wnt4 in immature HPCs and showed that the absence of Wnt4 led to a decreased expression of four ..
  43. 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
  44. 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...
  45. Daneman R, Agalliu D, Zhou L, Kuhnert F, Kuo C, Barres B. Wnt/beta-catenin signaling is required for CNS, but not non-CNS, angiogenesis. Proc Natl Acad Sci U S A. 2009;106:641-6 pubmed publisher
    ..Taken together these experiments reveal an essential role for Wnt/beta-catenin signaling in driving CNS-specific angiogenesis and provide molecular evidence that angiogenesis and BBB formation are in part linked. ..
  46. 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. ..