Gene Symbol: Dkk4
Description: dickkopf WNT signaling pathway inhibitor 4
Alias: Dkk-4, dickkopf-related protein 4, dickkopf homolog 4, dickkopf-4
Species: mouse
Products:     Dkk4

Top Publications

  1. Bazzi H, Fantauzzo K, Richardson G, Jahoda C, Christiano A. The Wnt inhibitor, Dickkopf 4, is induced by canonical Wnt signaling during ectodermal appendage morphogenesis. Dev Biol. 2007;305:498-507 pubmed
    ..5 and E15.5. One of the significantly differentially expressed genes was the Wnt inhibitor Dickkopf 4, Dkk4...
  2. Zuklys S, Gill J, Keller M, Hauri Hohl M, Zhanybekova S, Balciunaite G, et al. Stabilized beta-catenin in thymic epithelial cells blocks thymus development and function. J Immunol. 2009;182:2997-3007 pubmed publisher
    ..These results suggest that a precise regulation of canonical Wnt signaling in thymic epithelia is essential for normal thymus development and function. ..
  3. Cui C, Hashimoto T, Grivennikov S, Piao Y, Nedospasov S, Schlessinger D. Ectodysplasin regulates the lymphotoxin-beta pathway for hair differentiation. Proc Natl Acad Sci U S A. 2006;103:9142-7 pubmed
    ..They included Shh and its effectors, as well as antagonists for the Wnt (Dkk4) and BMP (Sostdc1) pathways...
  4. Li C, Lan Y, Krumlauf R, Jiang R. Modulating Wnt Signaling Rescues Palate Morphogenesis in Pax9 Mutant Mice. J Dent Res. 2017;96:1273-1281 pubmed publisher
    ..Together, these data identify a crucial role for canonical Wnt signaling in acting downstream of Pax9 to regulate palate morphogenesis. ..
  5. Cui C, Yin M, Sima J, Childress V, Michel M, Piao Y, et al. Involvement of Wnt, Eda and Shh at defined stages of sweat gland development. Development. 2014;141:3752-60 pubmed publisher
    ..The Wnt antagonist Dkk4 appeared to inhibit this induction: Dkk4 was sharply downregulated in β-catenin-ablated mice, indicating that it ..
  6. Chen D, Jarrell A, Guo C, Lang R, Atit R. Dermal ?-catenin activity in response to epidermal Wnt ligands is required for fibroblast proliferation and hair follicle initiation. Development. 2012;139:1522-33 pubmed publisher
    ..These data reveal functional roles for dermal Wnt signaling/?-catenin in fibroblast proliferation and in the epidermal hair follicle initiation program. ..
  7. Suomalainen M, Thesleff I. Patterns of Wnt pathway activity in the mouse incisor indicate absence of Wnt/beta-catenin signaling in the epithelial stem cells. Dev Dyn. 2010;239:364-72 pubmed publisher
    ..We conclude that epithelial stem cells in the mouse incisors are not regulated directly by Wnt/beta-catenin signaling. ..
  8. Porntaveetus T, Ohazama A, Choi H, Herz J, Sharpe P. Wnt signaling in the murine diastema. Eur J Orthod. 2012;34:518-24 pubmed publisher
    ..Wnt signaling is thus usually attenuated in the diastema by these secreted and membrane bound Wnt inhibitors...
  9. Lefebvre S, Fliniaux I, Schneider P, Mikkola M. Identification of ectodysplasin target genes reveals the involvement of chemokines in hair development. J Invest Dermatol. 2012;132:1094-102 pubmed publisher
    ..Deficiency in cxcR3 resulted in decreased primary hair follicle density but otherwise normal hair development, indicating that chemokine signaling influences the patterning of primary hair placodes only. ..

More Information


  1. Iwata J, Suzuki A, Yokota T, Ho T, Pelikan R, Urata M, et al. TGF? regulates epithelial-mesenchymal interactions through WNT signaling activity to control muscle development in the soft palate. Development. 2014;141:909-17 pubmed publisher
    ..Gene expression of Dickkopf (Dkk1 and Dkk4), negative regulators of WNT-?-catenin signaling, is upregulated in the soft palate of Tgfbr2(fl/fl);K14-Cre mice, ..
  2. Hiramitsu S, Terauchi M, Kubota T. The effects of Dickkopf-4 on the proliferation, differentiation, and apoptosis of osteoblasts. Endocrinology. 2013;154:4618-26 pubmed publisher
    The Dickkopf family of proteins is comprised of four members (Dkk1, Dkk2, Dkk3, Dkk4) that are known to modulate Wnt/?-catenin signaling, which is activated during bone formation...
  3. Reid B, Yang H, Melvin V, Taketo M, Williams T. Ectodermal Wnt/?-catenin signaling shapes the mouse face. Dev Biol. 2011;349:261-9 pubmed publisher
  4. Zhang Y, Tomann P, Andl T, Gallant N, Huelsken J, Jerchow B, et al. Reciprocal requirements for EDA/EDAR/NF-kappaB and Wnt/beta-catenin signaling pathways in hair follicle induction. Dev Cell. 2009;17:49-61 pubmed publisher
    ..These data reveal a complex interplay and interdependence of Wnt/beta-catenin and EDA/EDAR/NF-kappaB signaling pathways in initiation and maintenance of primary hair follicle placodes...
  5. Fliniaux I, Mikkola M, Lefebvre S, Thesleff I. Identification of dkk4 as a target of Eda-A1/Edar pathway reveals an unexpected role of ectodysplasin as inhibitor of Wnt signalling in ectodermal placodes. Dev Biol. 2008;320:60-71 pubmed publisher
    ..Surprisingly, there were only two genes with obvious involvement in Wnt pathway: dkk4 (most highly induced gene in the screen), and lrp4...
  6. Cui C, Kunisada M, Piao Y, Childress V, Ko M, Schlessinger D. Dkk4 and Eda regulate distinctive developmental mechanisms for subtypes of mouse hair. PLoS ONE. 2010;5:e10009 pubmed publisher
    ..We report that Dickkopf 4 (Dkk4), a Wnt antagonist, affects an auxiliary pathway for Eda-independent development of secondary hair...
  7. Diep D, Hoen N, Backman M, Machon O, Krauss S. Characterisation of the Wnt antagonists and their response to conditionally activated Wnt signalling in the developing mouse forebrain. Brain Res Dev Brain Res. 2004;153:261-70 pubmed
    ..At later developmental stages (E15.5, E17.5, and P0), little or no expression of dkk1, dkk2, and dkk4 was found in the forebrain, while dkk3 expression was detected in the ventricular zone (VZ) of the lateral and III ..
  8. Heath J, Langton A, Hammond N, Overbeek P, Dixon M, Headon D. Hair follicles are required for optimal growth during lateral skin expansion. J Invest Dermatol. 2009;129:2358-64 pubmed publisher
    ..Thus, in addition to their role in wound repair, HFs can make a significant contribution to lateral expansion of the IFE in the absence of trauma. ..
  9. Shirokova V, Biggs L, Jussila M, Ohyama T, Groves A, Mikkola M. Foxi3 Deficiency Compromises Hair Follicle Stem Cell Specification and Activation. Stem Cells. 2016;34:1896-908 pubmed publisher
    ..Thus, Foxi3 regulates multiple aspects of hair follicle development and homeostasis. Stem Cells 2016;34:1896-1908. ..
  10. Suresh S, Durakoglugil D, Zhou X, Zhu B, Comerford S, Xing C, et al. SRC-2-mediated coactivation of anti-tumorigenic target genes suppresses MYC-induced liver cancer. PLoS Genet. 2017;13:e1006650 pubmed publisher
    ..We demonstrate that activation of SHP (Small Heterodimer Partner), DKK4 (Dickkopf-4), and CADM4 (Cell Adhesion Molecule 4) by SRC-2 suppresses tumorigenesis in vitro and in vivo...
  11. Fantauzzo K, Christiano A. Trps1 activates a network of secreted Wnt inhibitors and transcription factors crucial to vibrissa follicle morphogenesis. Development. 2012;139:203-14 pubmed publisher
    ..Our findings identify Trps1 as a novel regulator of the Wnt signaling pathway and of early hair follicle progenitors in the developing vibrissa follicle. ..
  12. Wong E, Cui L, Ng C, Tang C, Liu X, So M, et al. Genome-wide copy number variation study in anorectal malformations. Hum Mol Genet. 2013;22:621-31 pubmed publisher
    ..Gene-based analysis revealed 79 genes interfered by CNVs in patients only. In particular, we identified a de novo DKK4 duplication...
  13. Huh S, Närhi K, Lindfors P, Häärä O, Yang L, Ornitz D, et al. Fgf20 governs formation of primary and secondary dermal condensations in developing hair follicles. Genes Dev. 2013;27:450-8 pubmed publisher
  14. Sima J, Piao Y, Chen Y, Schlessinger D. Molecular dynamics of Dkk4 modulates Wnt action and regulates meibomian gland development. Development. 2016;143:4723-4735 pubmed
    ..However, the molecular function of other Dkks remains largely unknown. Here, we show that Dkk4 selectively inhibits a subset of Wnts, but is further inactivated by proteolytic cleavage...
  15. Voutilainen M, Lindfors P, Trela E, Lönnblad D, Shirokova V, Elo T, et al. Ectodysplasin/NF-κB Promotes Mammary Cell Fate via Wnt/β-catenin Pathway. PLoS Genet. 2015;11:e1005676 pubmed publisher
    ..Using an ex vivo culture system, we show that suppression of canonical Wnt signalling leads to a dose-dependent inhibition of supernumerary placodes in K14-Eda tissue explants. ..
  16. Glover J, Wells K, Matthäus F, Painter K, Ho W, Riddell J, et al. Hierarchical patterning modes orchestrate hair follicle morphogenesis. PLoS Biol. 2017;15:e2002117 pubmed publisher
    ..This work illustrates a hierarchy of periodic patterning modes operating in organogenesis. ..