Gene Symbol: Dkk2
Description: dickkopf WNT signaling pathway inhibitor 2
Alias: dickkopf-related protein 2, dickkopf 2, dickkopf homolog 1, dickkopf homolog 2, dkk-2, mDkk-2
Species: mouse
Products:     Dkk2

Top Publications

  1. Kumar S, Duester G. Retinoic acid signaling in perioptic mesenchyme represses Wnt signaling via induction of Pitx2 and Dkk2. Dev Biol. 2010;340:67-74 pubmed publisher
    ..Several Wnt signaling components are expressed in ocular tissues during eye development including Dkk2, encoding an inhibitor of Wnt/beta-catenin signaling, which was previously shown to be induced by Pitx2 in the ..
  2. Min J, Park H, Choi H, Kim Y, Pyun B, Agrawal V, et al. The WNT antagonist Dickkopf2 promotes angiogenesis in rodent and human endothelial cells. J Clin Invest. 2011;121:1882-93 pubmed publisher
    ..Here, we report that Dickkopf1 (DKK1) and Dickkopf2 (DKK2), originally known as WNT antagonists, play opposite functional roles in regulating angiogenesis...
  3. Huang J, Dattilo L, Rajagopal R, Liu Y, Kaartinen V, Mishina Y, et al. FGF-regulated BMP signaling is required for eyelid closure and to specify conjunctival epithelial cell fate. Development. 2009;136:1741-50 pubmed publisher
    ..A second row of eyelashes is a feature of human lymphedema-distichiasis syndrome, which is associated with mutations in FOXC2...
  4. Mukhopadhyay M, Gorivodsky M, Shtrom S, Grinberg A, Niehrs C, Morasso M, et al. Dkk2 plays an essential role in the corneal fate of the ocular surface epithelium. Development. 2006;133:2149-54 pubmed
    ..Here, we show that Dkk2-mediated repression of the Wnt/beta-catenin pathway is essential to promote differentiation of the corneal ..
  5. Gage P, Qian M, Wu D, Rosenberg K. The canonical Wnt signaling antagonist DKK2 is an essential effector of PITX2 function during normal eye development. Dev Biol. 2008;317:310-24 pubmed publisher
    ..Here we show that Dkk2, encoding an antagonist of canonical Wnt signaling, is an essential downstream target of the PITX2 homeodomain ..
  6. 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
    ..In situ hybridisation on sections from E12 embryos showed an expression of dkk2 in the thalamus and dkk3 in the cortical hem and thalamus. At later developmental stages (E15.5, E17...
  7. 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
    ..Secreted Wnt inihibitors Dkk1, Dkk2, and Dkk3 were also expressed in the diastema...
  8. Fujita K, Janz S. Attenuation of WNT signaling by DKK-1 and -2 regulates BMP2-induced osteoblast differentiation and expression of OPG, RANKL and M-CSF. Mol Cancer. 2007;6:71 pubmed
    ..Focally increased Dkk1 production by tumor cells in the bone may thus lead to focal bone loss. ..
  9. Meng Q, Jin C, Chen Y, Chen J, Medvedovic M, Xia Y. Expression of signaling components in embryonic eyelid epithelium. PLoS ONE. 2014;9:e87038 pubmed publisher
    ..expression of adenomatosis polyposis coli down-regulated 1 (Apcdd1), but the IE cells had high expression of Dkk2. Our results suggest that the functionally distinct LE and IE cells have also differential expression of signaling ..

More Information


  1. Park H, Jung H, Choi H, Kim D, Yoo J, Yun C, et al. Distinct roles of DKK1 and DKK2 in tumor angiogenesis. Angiogenesis. 2014;17:221-34 pubmed publisher
    ..We have previously shown that Dickkopf-1 (DKK1), a Wnt antagonist, inhibits and its homolog DKK2 enhances, angiogenesis in normal tissues...
  2. Ang S, Stump R, Lovicu F, McAvoy J. Spatial and temporal expression of Wnt and Dickkopf genes during murine lens development. Gene Expr Patterns. 2004;4:289-95 pubmed
    ..This is most notable for Wnt5a, which is barely detectable in the central lens epithelium at P21. Dkk1, Dkk2 and Dkk3 have similar patterns of expression to each other and to the majority of the Wnts during lens development...
  3. Wang Y, Fang R, Yuan Y, Pan M, Hu M, Zhou Y, et al. Identification of host proteins, Spata3 and Dkk2, interacting with Toxoplasma gondii micronemal protein MIC3. Parasitol Res. 2016;115:2825-35 pubmed publisher
    ..Two of which, spermatogenesis-associated protein 3 (Spata3) and dickkopf-related protein 2 (Dkk2), were further confirmed to interact with MIC3 by additional protein-protein interaction tests...
  4. Nie X, Luukko K, Fjeld K, Kvinnsland I, Kettunen P. Developmental expression of Dkk1-3 and Mmp9 and apoptosis in cranial base of mice. J Mol Histol. 2005;36:419-26 pubmed
    ..The expression was downregulated in postnatal stages. Dkk2 was localized in the perichondral mesenchyme outlining the anterior cranial base in embryogenesis...
  5. Maass T, Marquardt J, Lee J, Krupp M, Scholz Kreisel P, Mogler C, et al. Increased liver carcinogenesis and enrichment of stem cell properties in livers of Dickkopf 2 (Dkk2) deleted mice. Oncotarget. 2016;7:28903-13 pubmed publisher
    b>Dkk2 a antagonist of the Wnt/β-catenin-signaling pathway was shown to be silenced in diverse cancers. More recent data indicate that Dkk family members may also possess functions independent of Wnt-signaling during carcinogenesis...
  6. Li J, Huang X, Xu X, Mayo J, Bringas P, Jiang R, et al. SMAD4-mediated WNT signaling controls the fate of cranial neural crest cells during tooth morphogenesis. Development. 2011;138:1977-89 pubmed publisher
    ..Taken together, our study demonstrates that SMAD4 plays a crucial role in regulating the interplay between TGF?/BMP and WNT signaling to ensure the proper CNC cell fate decision during organogenesis...
  7. Mao B, Wu W, Li Y, Hoppe D, Stannek P, Glinka A, et al. LDL-receptor-related protein 6 is a receptor for Dickkopf proteins. Nature. 2001;411:321-5 pubmed
    ..Here we show that LRP6 (ref. 7) is a specific, high-affinity receptor for Dkk1 and Dkk2. Dkk1 blocks LRP6-mediated Wnt/beta-catenin signalling by interacting with domains that are distinct from those ..
  8. Li X, Shan J, Chang W, Kim I, Bao J, Lee H, et al. Chemical and genetic evidence for the involvement of Wnt antagonist Dickkopf2 in regulation of glucose metabolism. Proc Natl Acad Sci U S A. 2012;109:11402-7 pubmed publisher
    ..This Dkk inhibitor appeared to act through DKK2 because the inhibitor exerted no additional effects on glucose metabolism in the Dkk2(-/-) mice...
  9. Zhang Y, Peng S, Kuang H, Chen Q, Liu S, Zhang L, et al. Expression and regulation of Dickkopf2 during periimplantation in mice. J Reprod Dev. 2009;55:17-22 pubmed
    ..Dickkopf2 (Dkk2) is a member of Dickkopf family normally acting as an antagonist of canonical Wnt/beta-catenin signaling, which has ..
  10. Chen L, Wang K, Shao Y, Huang J, Li X, Shan J, et al. Structural insight into the mechanisms of Wnt signaling antagonism by Dkk. J Biol Chem. 2008;283:23364-70 pubmed publisher
    ..Using NMR spectroscopy, we determined the solution structure of the C-terminal cysteine-rich domain of mouse Dkk2 (Dkk2C)...
  11. Li X, Liu P, Liu W, Maye P, Zhang J, Zhang Y, et al. Dkk2 has a role in terminal osteoblast differentiation and mineralized matrix formation. Nat Genet. 2005;37:945-52 pubmed
    ..Wnt signaling promotes bone formation, but we found that mice lacking the canonical Wnt antagonist Dickkopf2 (Dkk2) were osteopenic...
  12. Bluske K, Kawakami Y, Koyano Nakagawa N, Nakagawa Y. Differential activity of Wnt/beta-catenin signaling in the embryonic mouse thalamus. Dev Dyn. 2009;238:3297-309 pubmed publisher
    ..Analysis of mice with enhanced or reduced Shh signal showed that Axin2 expression is similar to controls. These results suggest that differential Wnt signaling may play a role in patterning the thalamus independent of Shh signaling. ..
  13. Fukusumi Y, Meier F, Götz S, Matheus F, Irmler M, Beckervordersandforth R, et al. Dickkopf 3 Promotes the Differentiation of a Rostrolateral Midbrain Dopaminergic Neuronal Subset In Vivo and from Pluripotent Stem Cells In Vitro in the Mouse. J Neurosci. 2015;35:13385-401 pubmed publisher
  14. Nie X. Dkk1, -2, and -3 expression in mouse craniofacial development. J Mol Histol. 2005;36:367-72 pubmed
    ..Their expression patterns suggest important roles in these processes; further study is warranted to elucidate these roles. ..
  15. Li L, Mao J, Sun L, Liu W, Wu D. Second cysteine-rich domain of Dickkopf-2 activates canonical Wnt signaling pathway via LRP-6 independently of dishevelled. J Biol Chem. 2002;277:5977-81 pubmed
    ..All the evidence indicates that Dkk-2C2 signals through LRP proteins, which does not require Dvl, while Wnt protein may employ both Dvl, presumably through Fz, and LRP to achieve more efficient signal transduction. ..
  16. 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
    ..This information has important implications for prevention and non-surgical correction of cleft soft palate. ..
  17. Monaghan A, Kioschis P, Wu W, Zuniga A, Bock D, Poustka A, et al. Dickkopf genes are co-ordinately expressed in mesodermal lineages. Mech Dev. 1999;87:45-56 pubmed
    ..Our observations indicate that dkk genes constitute a new family of secreted proteins that may mediate inductive interactions between epithelial and mesenchymal cells. ..
  18. Jia S, Zhou J, Fanelli C, Wee Y, Bonds J, Schneider P, et al. Small-molecule Wnt agonists correct cleft palates in Pax9 mutant mice in utero. Development. 2017;144:3819-3828 pubmed publisher
    ..We show that the absence of Pax9 alters the expression of Wnt pathway genes including Dkk1 and Dkk2, proven antagonists of Wnt signaling...
  19. Jia S, Zhou J, Gao Y, Baek J, Martin J, Lan Y, et al. Roles of Bmp4 during tooth morphogenesis and sequential tooth formation. Development. 2013;140:423-32 pubmed publisher
    ..In addition, we found that the Wnt inhibitors Dkk2 and Wif1 were much more abundantly expressed in the mandibular than maxillary molar mesenchyme in wild-type embryos ..
  20. 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. ..
  21. Fjeld K, Kettunen P, Furmanek T, Kvinnsland I, Luukko K. Dynamic expression of Wnt signaling-related Dickkopf1, -2, and -3 mRNAs in the developing mouse tooth. Dev Dyn. 2005;233:161-6 pubmed
    ..During molar morphogenesis Dkk1 was detected in the dental mesenchyme, including the preodontoblasts. Dkk2 was seen in the dental papilla, whereas Dkk3 was specifically expressed in the putative epithelial signaling ..
  22. Phillips M, Mukhopadhyay M, Poscablo C, Westphal H. Dkk1 and Dkk2 regulate epicardial specification during mouse heart development. Int J Cardiol. 2011;150:186-92 pubmed publisher
    Dkk1 and Dkk2 interact with LRP5 and LRP6 to modulate canonical Wnt signaling during development, and are known to be expressed in the developing heart...
  23. Jia S, Kwon H, Lan Y, Zhou J, Liu H, Jiang R. Bmp4-Msx1 signaling and Osr2 control tooth organogenesis through antagonistic regulation of secreted Wnt antagonists. Dev Biol. 2016;420:110-119 pubmed publisher
    ..Remarkably, both Dkk2 and Sfrp2 exhibit Osr2-dependent preferential expression on the lingual side of the tooth bud mesenchyme and ..
  24. Hägglund A, Jones I, Carlsson L. A novel mouse model of anterior segment dysgenesis (ASD): conditional deletion of Tsc1 disrupts ciliary body and iris development. Dis Model Mech. 2017;10:245-257 pubmed publisher
  25. Kwon H, Jia S, Lan Y, Liu H, Jiang R. Activin and Bmp4 Signaling Converge on Wnt Activation during Odontogenesis. J Dent Res. 2017;96:1145-1152 pubmed publisher
    ..of tooth morphogenesis through antagonistic regulation of expression of secreted Wnt antagonists, including Dkk2 and Sfrp2, in the developing tooth mesenchyme...
  26. Jin C, Chen J, Meng Q, Carreira V, Tam N, Geh E, et al. Deciphering gene expression program of MAP3K1 in mouse eyelid morphogenesis. Dev Biol. 2013;374:96-107 pubmed publisher
    ..Using LCM and expression array, our studies have uncovered novel molecular signatures of MAP3K1 in embryonic eyelid closure. ..
  27. Grumolato L, Liu G, Mong P, Mudbhary R, Biswas R, Arroyave R, et al. Canonical and noncanonical Wnts use a common mechanism to activate completely unrelated coreceptors. Genes Dev. 2010;24:2517-30 pubmed publisher
    ..Thus, different Wnts, through their specific coupling and phosphorylation of unrelated coreceptors, activate completely distinct signaling pathways. ..
  28. Meng Q, Mongan M, Carreira V, Kurita H, Liu C, Kao W, et al. Eyelid closure in embryogenesis is required for ocular adnexa development. Invest Ophthalmol Vis Sci. 2014;55:7652-61 pubmed publisher
    ..These mice, including systemic ablation of Map3k1 and Dkk2, ocular surface epithelium (OSE) knockout of c-Jun and Egfr, conditional knockout of Shp2 in stratified epithelium (..
  29. Miyagawa S, Matsumaru D, Murashima A, Omori A, Satoh Y, Haraguchi R, et al. The role of sonic hedgehog-Gli2 pathway in the masculinization of external genitalia. Endocrinology. 2011;152:2894-903 pubmed publisher
    ..The current study identified hedgehog signaling pathway as a key factor not only for initial development but also for sexually dimorphic development of the external genitalia in coordination with androgen signaling. ..
  30. Pietilä I, Ellwanger K, Railo A, Jokela T, Barrantes I, Shan J, et al. Secreted Wnt antagonist Dickkopf-1 controls kidney papilla development coordinated by Wnt-7b signalling. Dev Biol. 2011;353:50-60 pubmed publisher
    ..Based on the results, we propose that Dkk1 controls the degree of Wnt-7b signalling in the papilla to coordinate kidney organogenesis. ..
  31. Gage P, Kuang C, Zacharias A. The homeodomain transcription factor PITX2 is required for specifying correct cell fates and establishing angiogenic privilege in the developing cornea. Dev Dyn. 2014;243:1391-400 pubmed publisher
    ..PITX2 is also required to establish angiogenic privilege in the developing cornea. Further, the expression of Dkk2 and suppression of canonical Wnt signaling activity levels are key mechanisms by which PITX2 specifies ocular ..
  32. 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. ..