Secreted and transmembrane Wnt inhibitors and activators

Cold Spring Harbor Perspectives in Biology

Volumn 5, Issue 3, 2013, Pages

  Cruciat, Cristina Maria ^a   Niehrs, Christof ^a,b  

^a GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^b INSTITUTE OF MOLECULAR BIOLOGY   (Armenia)

Author keywords

[No Author keywords available]

Indexed keywords

DKK1 PROTEIN, XENOPUS; FRIZZLED PROTEIN; MEMBRANE PROTEIN; SIGNAL PEPTIDE; WNT PROTEIN; XENOPUS PROTEIN;

ANIMAL; BIOLOGICAL MODEL; DRUG ANTAGONISM; DRUG POTENTIATION; EMBRYO DEVELOPMENT; GENETICS; HOMEOSTASIS; HUMAN; METABOLISM; PHYSIOLOGY; PROTEIN TERTIARY STRUCTURE; REVIEW; WNT SIGNALING PATHWAY;

ANIMALS; EMBRYONIC DEVELOPMENT; HOMEOSTASIS; HUMANS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; MEMBRANE GLYCOPROTEINS; MODELS, BIOLOGICAL; PROTEIN STRUCTURE, TERTIARY; RECEPTORS, WNT; WNT PROTEINS; WNT SIGNALING PATHWAY; XENOPUS PROTEINS;

EID: 84866092742     PISSN: None     EISSN: 19430264     Source Type: Journal    
DOI: 10.1101/cshperspect.a015081     Document Type: Article

References (240)

1. Adamska M, MacDonald BT, Sarmast ZH, Oliver ER, Meisler MH. 2004. En1 and Wnt7a interact with Dkk1 during limb development in the mouse. Dev Biol 272: 134-144.
2. Aguilera O, Fraga MF, Ballestar E, Paz MF, Herranz M, Espada J, Garcia JM, Munoz A, Esteller M, Gonzalez-Sancho JM. 2006. Epigenetic inactivation of the Wnt antagonist DICKKOPF-1 (DKK-1) gene in human colorectal cancer. Oncogene 25: 4116-4121.
3. Ahn Y, Sanderson BW, Klein OD, Krumlauf R. 2010. Inhibition of Wnt signaling by Wise (Sostdc1) and negative feedback from Shh controls tooth number and patterning. Development 137: 3221-3231.
4. Ai M, Holmen SL, Van Hul W, Williams BO, Warman ML. 2005. Reduced affinity to and inhibition by DKK1 form a common mechanism by which high bone mass-associated missense mutations in LRP5 affect canonical Wnt signaling. Mol Cell Biol 25: 4946-4955.
5. Aoki M, Mieda M, Ikeda T, Hamada Y, Nakamura H, Okamoto H. 2007. R-Spondin3 is required for mouse placental development. Dev Biol 301: 218-226.
6. Aoki M, Kiyonari H, Nakamura H, Okamoto H. 2008. R- Spondin2 expression in the apical ectodermal ridge is essential for outgrowth and patterning in mouse limb development. Dev Growth Differ 50: 85-95.
7. Avsian-Kretchmer O, Hsueh AJ. 2004. Comparative genomic analysis of the eight-membered ring cystine knotcontaining bone morphogenetic protein antagonists. Mol Endocrinol 18: 1-12.
8. Bafico A, Gazit A, Pramila T, Finch PW, Yaniv A, Aaronson SA. 1999. Interaction of frizzled related protein (FRP) with Wnt ligands and the frizzled receptor suggests alternative mechanisms for FRP inhibition of Wnt signaling. J Biol Chem 274: 16180-16187.
9. Bafico A, Liu G, Yaniv A, Gazit A, Aaronson SA. 2001. Novel mechanism of Wnt signalling inhibition mediated by Dickkopf-1 interaction with LRP6/Arrow. Nat Cell Biol 3: 683-686.
10. Balemans W, Ebeling M, Patel N, Van Hul E, Olson P, Dioszegi M, Lacza C, Wuyts W, Van Den Ende J, Willems P, et al. 2001. Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet 10: 537-543.
11. Balemans W, Patel N, Ebeling M, Van Hul E, Wuyts W, Lacza C, Dioszegi M, Dikkers FG, Hildering P, Willems PJ, et al. 2002. Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease. J Med Genet 39: 91-97.
12. Banyai L, Patthy L. 1999. The NTR module: Domains of netrins, secreted frizzled related proteins, and type I procollagen C-proteinase enhancer protein are homologous with tissue inhibitors of metalloproteases. Protein Sci 8: 1636-1642.
13. Baran R, Kechijian P. 2001. Understanding nail disorders. Eur J Dermatol 11: 159-162.
14. Barker N, Clevers H. 2010. Leucine-rich repeat-containing G-protein-coupled receptors as markers of adult stem cells. Gastroenterology 138: 1681-1696.
15. Barrantes Idel B, Montero-Pedrazuela A, Guadano-Ferraz A, Obregon MJ, Martinez de Mena R, Gailus-Durner V, Fuchs H, Franz TJ, Kalaydjiev S, Klempt M, et al. 2006. Generation and characterization of dickkopf3 mutant mice. Mol Cell Biol 26: 2317-2326.
16. Barrow JR, Thomas KR, Boussadia-Zahui O, Moore R, Kemler R, Capecchi MR, McMahon AP. 2003. Ectodermal Wnt3/β-catenin signaling is required for the establishment and maintenance of the apical ectodermal ridge. Genes Dev 17: 394-409.
17. Bell SM, Schreiner CM, Wert SE, Mucenski ML, Scott WJ, Whitsett JA. 2008. R-Spondin 2 is required for normal laryngeal-tracheal, lung and limb morphogenesis. Development 135: 1049-1058.
18. Belo JA, Bachiller D, Agius E, Kemp C, Borges AC, Marques S, Piccolo S, De Robertis EM. 2000. Cerberuslike is a secreted BMP and nodal antagonist not essential for mouse development. Genesis 26: 265-270.
19. Belo JA, Silva AC, Borges AC, Filipe M, Bento M, Goncalves L, Vitorino M, Salgueiro AM, Texeira V, Tavares AT, et al. 2009. Generating asymmetries in the early vertebrate embryo: The role of the Cerberus-like family. Int J Dev Biol 53: 1399-1407.
20. Berger W. 1998. Molecular dissection of Norrie disease. Acta Anat (Basel) 162: 95-100.
21. Berger W, Meindl A, van de Pol TJ, Cremers FP, Ropers HH, Doerner C, Monaco A, Bergen AA, Lebo R, Warburgh M, et al. 1992. Isolation of a candidate gene for Norrie disease by positional cloning. Nat Genet 2: 84.
22. Bergmann C, Senderek J, Anhuf D, Thiel CT, Ekici AB, Poblete-Gutierrez P, van Steensel M, Seelow D, Nurnberg G, Schild HH, et al. 2006. Mutations in the gene encoding the Wnt-signaling component R-spondin 4 (RSPO4) cause autosomal recessive anonychia. Am J Hum Genet 79: 1105-1109.
23. Bhat RA, Stauffer B, Komm BS, Bodine PV. 2007. Structurefunction analysis of secreted frizzled-related protein-1 for its Wnt antagonist function. J Cell Biochem 102: 1519-1528.
24. Binnerts ME, Kim KA, Bright JM, Patel SM, Tran K, Zhou M, Leung JM, Liu Y, Lomas WE III, Dixon M, et al. 2007. R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6. Proc Natl Acad Sci 104: 14700-14705.
25. Blaydon DC, Ishii Y, O'Toole EA, Unsworth HC, Teh MT, Ruschendorf F, Sinclair C, Hopsu-Havu VK, Tidman N, Moss C, et al. 2006. The gene encoding R-spondin 4 (RSPO4), a secreted protein implicated in Wnt signaling, is mutated in inherited anonychia. Nat Genet 38: 1245-1247.
26. Blish KR, Wang W, Willingham MC, Du W, Birse CE, Krishnan SR, Brown JC, Hawkins GA, Garvin AJ, D'Agostino RB Jr, et al. 2008. A human bone morphogenetic protein antagonist is down-regulated in renal cancer. Mol Biol Cell 19: 457-464.
27. Bouwmeester T, Kim S, Sasai Y, Lu B, De Robertis EM. 1996. Cerberus is a head-inducing secreted factor expressed in the anterior endoderm of Spemann's organizer. Nature 382: 595-601.
28. Bovolenta P, Esteve P, Ruiz JM, Cisneros E, Lopez-Rios J. 2008. Beyond Wnt inhibition: New functions of secreted Frizzled-related proteins in development and disease. J Cell Sci 121: 737-746.
29. Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, Wu D, Insogna K, Lifton RP. 2002. High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med 346: 1513-1521.
30. Bradley L, Sun B, Collins-Racie L, LaVallie E, McCoy J, Sive H. 2000. Different activities of the frizzled-related proteins frzb2 and sizzled2 during Xenopus anteroposterior patterning. Dev Biol 227: 118-132.
31. Brott BK, Sokol SY. 2002. Regulation of Wnt/LRP signaling by distinct domains of Dickkopf proteins. Mol Cell Biol 22: 6100-6110.
32. Bruchle NO, Frank J, Frank V, Senderek J, Akar A, Koc E, Rigopoulos D, van Steensel M, Zerres K, Bergmann C. 2008. RSPO4 is the major gene in autosomal-recessive anonychia and mutations cluster in the furin-like cysteine-rich domains of the Wnt signaling ligand R-spondin 4. J Invest Dermatol 128: 791-796.
33. Brunkow ME, Gardner JC, Van Ness J, Paeper BW, Kovacevich BR, Proll S, Skonier JE, Zhao L, Sabo PJ, Fu Y, et al. 2001. Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet 68: 577-589.
34. Cappuccio I, Calderone A, Busceti CL, Biagioni F, Pontarelli F, Bruno V, Storto M, Terstappen GT, Gaviraghi G, Fornai F, et al. 2005. Induction of Dickkopf-1, a negative modulator of the Wnt pathway, is required for the development of ischemic neuronal death. J Neurosci 25: 2647-2657.
35. Caricasole A, Copani A, Caraci F, Aronica E, Rozemuller AJ, Caruso A, Storto M, Gaviraghi G, Terstappen GC, Nicoletti F. 2004. Induction of Dickkopf-1, a negative modulator of the Wnt pathway, is associated with neuronal degeneration in Alzheimer's brain. J Neurosci 24: 6021-6027.
36. Carmon KS, Gong X, Lin Q, Thomas A, Liu Q. 2011. R- Spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/β-catenin signaling. Proc Natl Acad Sci 108: 11452-11457.
37. Carmon KS, Lin Q, Gong X, Thomas A, Liu Q. 2012. LGR5 interacts and cointernalizes with Wnt receptors to modulate Wnt/β-catenin signaling. Mol Cell Biol 32: 2054-2064.
38. Chapman SC, Brown R, Lees L, Schoenwolf GC, Lumsden A. 2004. Expression analysis of chick Wnt and Frizzled genes and selected inhibitors in early chick patterning. Dev Dyn 229: 668-676.
39. Chassot AA, Ranc F, Gregoire EP, Roepers-Gajadien HL, Taketo MM, Camerino G, de Rooij DG, Schedl A, Chaboissier MC. 2008. Activation of β-catenin signaling by Rspo1 controls differentiation of the mammalian ovary. Hum Mol Genet 17: 1264-1277.
40. Chen ZY, Hendriks RW, Jobling MA, Powell JF, Breakefield XO, Sims KB, Craig IW. 1992. Isolation and characterization of a candidate gene for Norrie disease. Nat Genet 1: 204-208.
41. Chen ZY, Battinelli EM, Fielder A, Bundey S, Sims K, Breakefield XO, Craig IW. 1993. A mutation in the Norrie disease gene (NDP) associated with X-linked familial exudative vitreoretinopathy. Nat Genet 5: 180-183.
42. Chen JZ, Wang S, Tang R, Yang QS, Zhao E, Chao Y, Ying K, Xie Y, Mao YM. 2002. Cloning and identification of a cDNA that encodes a novel human protein with thrombospondin type I repeat domain, hPWTSR. Mol Biol Rep 29: 287-292.
43. Chien AJ, Conrad WH, Moon RT. 2009. A Wnt survival guide: From flies to human disease. J Invest Dermatol 129: 1614-1627.
44. Chong JM, Uren A, Rubin JS, Speicher DW. 2002. Disulfide bond assignments of secreted Frizzled-related protein-1 provide insights about Frizzled homology and netrin modules. J Biol Chem 277: 5134-5144.
45. Collette NM, Genetos DC, Murugesh D, Harland RM, Loots GG. 2010. Genetic evidence that SOST inhibits WNT signaling in the limb. Dev Biol 342: 169-179.
46. Dann CE, Hsieh JC, Rattner A, Sharma D, Nathans J, Leahy DJ. 2001. Insights into Wnt binding and signalling from the structures of two Frizzled cysteine-rich domains. Nature 412: 86-90.
47. Davidson G, Mao B, Del Barco Barrantes I, Niehrs C. 2002. Kremen proteins interact with Dickkopf1 to regulate anteroposterior CNS patterning. Development 129: 5587-5596.
48. de Lau W, Barker N, Low TY, Koo BK, Li VS, Teunissen H, Kujala P, Haegebarth A, Peters PJ, van de Wetering, et al. 2011. Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling. Nature 476: 293-297.
49. del Barco Barrantes I, Davidson G, Grone HJ, Westphal H, Niehrs C. 2003. Dkk1 and noggin cooperate in mammalian head induction. Genes Dev 17: 2239-2244.
50. Dennis S, Aikawa M, Szeto W, d'Amore PA, Papkoff J. 1999. A secreted Frizzled related protein, FrzA, selectively associates with Wnt-1 protein and regulates Wnt-1 signaling. J Cell Sci 112: 3815-3820.
51. De Robertis EM, Kuroda H. 2004. Dorsal-ventral patterning and neural induction in Xenopus embryos. Annu Rev Cell Dev Biol 20: 285-308.
52. Diep DB, Hoen N, Backman M, Machon O, Krauss S. 2004. Characterisation of the Wnt antagonists and their response to conditionally activated Wnt signalling in the developing mouse forebrain. Brain Res Dev Brain Res 153: 261-270.
53. Durai R, Davies M, Yang W, Yang SY, Seifalian A, Goldspink G, Winslet M. 2006. Biology of insulin-like growth factor binding protein-4 and its role in cancer (review). Int J Oncol 28: 1317-1325.
54. Ellies DL, Viviano B, McCarthy J, Rey JP, Itasaki N, Saunders S, Krumlauf R. 2006. Bone density ligand, Sclerostin, directly interacts with LRP5 but not LRP5G171V to modulate Wnt activity. J Bone Miner Res 21: 1738-1749.
55. Ellwanger K, Saito H, Clement-Lacroix P, Maltry N, Niedermeyer J, Lee WK, Baron R, Rawadi G, Westphal H, Niehrs C. 2008. Targeted disruption of the Wnt regulator Kremen induces limb defects and high bone density. Mol Cell Biol 28: 4875-4882.
56. Elston MS, Clifton-Bligh RJ. 2010. Identification of Wnt family inhibitors: A pituitary tumor directed whole genome approach. Mol Cell Endocrinol 326: 48-54.
57. Esteve P, Bovolenta P. 2010. The advantages and disadvantages of Sfrp1 and Sfrp2 expression in pathological events. Tohoku J Exp Med 221: 11-17.
58. Esteve P, Sandonis A, Cardozo M, Malapeira J, Ibanez C, Crespo I, Marcos S, Gonzalez-Garcia S, Toribio ML, Arribas J, et al. 2011. SFRPs act as negative modulators of ADAM10 to regulate retinal neurogenesis. Nat Neurosci 14: 562-569.
59. Fedders H, Augustin R, Bosch TC. 2004. A Dickkopf-3-related gene is expressed in differentiating nematocytes in the basal metazoan Hydra. Dev Genes Evol 214: 72-80.
60. Finch PW, He X, Kelley MJ, Uren A, Schaudies RP, Popescu NC, Rudikoff S, Aaronson SA, Varmus HE, Rubin JS. 1997. Purification and molecular cloning of a secreted, Frizzled-related antagonist of Wnt action. Proc Natl Acad Sci 94: 6770-6775.
61. Firth SM, Baxter RC. 2002. Cellular actions of the insulinlike growth factor binding proteins. Endocr Rev 23: 824-854.
62. Fjeld K, Kettunen P, Furmanek T, Kvinnsland IH, Luukko K. 2005. Dynamic expression of Wnt signaling-related Dickkopf1, -2, and -3 mRNAs in the developing mouse tooth. Dev Dyn 233: 161-166.
63. Fulciniti M, Tassone P, Hideshima T, Vallet S, Nanjappa P, Ettenberg SA, Shen Z, Patel N, Tai YT, Chauhan D, et al. 2009. Anti-DKK1 mAb (BHQ880) as a potential therapeutic agent for multiple myeloma. Blood 114: 371-379.
64. Furushima K, Yamamoto A, Nagano T, Shibata M, Miyachi H, Abe T, Ohshima N, Kiyonari H, Aizawa S. 2007. Mouse homologues of Shisa antagonistic to Wnt and Fgf signalings. Dev Biol 306: 480-492.
65. Galli LM, Barnes T, Cheng T, Acosta L, Anglade A, Willert K, Nusse R, Burrus LW. 2006. Differential inhibition of Wnt-3a by Sfrp-1, Sfrp-2, and Sfrp-3. Dev Dyn 235: 681-690.
66. Glinka A, Wu W, Onichtchouk D, Blumenstock C, Niehrs C. 1997. Head induction by simultaneous repression of Bmp and Wnt signalling in Xenopus. Nature 389: 517-519.
67. Glinka A, Wu W, Delius H, Monaghan AP, Blumenstock C, Niehrs C. 1998. Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction. Nature 391: 357-362.
68. Glinka A, Dolde C, Kirsch N, Huang YL, Kazanskaya O, Ingelfinger D, Boutros M, Cruciat CM, Niehrs C. 2011. LGR4 and LGR5 are R-spondin receptors mediating Wnt/β-catenin and Wnt/PCP signalling. EMBO Rep 12: 1055-1061.
69. Gong Y, Slee RB, Fukai N, Rawadi G, Roman-Roman S, Reginato AM, Wang H, Cundy T, Glorieux FH, Lev D, et al. 2001. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 107: 513-523.
70. Gonzalez-Sancho JM, Aguilera O, Garcia JM, Pendas-Franco N, Pena C, Cal S, Garcia de Herreros A, Bonilla F, Munoz A. 2005. The Wnt antagonist DICK-KOPF-1 gene is a downstream target of β-catenin/TCF and is downregulated in human colon cancer. Oncogene 24: 1098-1103.
71. Gordon A, Southam L, Loughlin J, Wilson AG, Stockley I, Hamer AJ, Eastell R, Wilkinson JM. 2007. Variation in the secreted frizzled-related protein-3 gene and risk of osteolysis and heterotopic ossification after total hip arthroplasty. J Orthop Res 25: 1665-1670.
72. Grotewold L, Ruther U. 2002. The Wnt antagonist Dickkopf-1 is regulated by Bmp signaling and c-Jun and modulates programmed cell death. EMBO J 21: 966-975.
73. Grotewold L, Theil T, Rüther U. 1999. Expression pattern of Dkk-1 during mouse limb development. Mech Dev 89: 151-153.
74. Guder C, Pinho S, Nacak TG, Schmidt HA, Hobmayer B, Niehrs C, Holstein TW. 2006. An ancient Wnt-Dickkopf antagonism in Hydra. Development 133: 901-911.
75. Guidato S, Itasaki N. 2007. Wise retained in the endoplasmic reticulum inhibits Wnt signaling by reducing cell surface LRP6. Dev Biol 310: 250-263.
76. Hackam AS. 2005. The Wnt signaling pathway in retinal degenerations. IUBMB Life 57: 381-388.
77. Han XH, Jin YR, Seto M, Yoon JK. 2011. AWNT/β-catenin signaling activator, R-spondin, plays positive regulatory roles during skeletal myogenesis. J Biol Chem 286: 10649- 10659.
78. Hao HX, Xie Y, Zhang Y, Charlat O, Oster E, Avello M, Lei H, Mickanin C, Liu D, Ruffner H, et al. 2012. ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner. Nature 485: 195-200.
79. Hashimoto H, Itoh M, Yamanaka Y, Yamashita S, Shimizu T, Solnica-Krezel L, Hibi M, Hirano T. 2000. Zebrafish Dkk1 functions in forebrain specification and axial mesendoderm formation. Dev Biol 217: 138-152.
80. Hashimoto H, Rebagliati M, Ahmad N, Muraoka O, Kurokawa T, Hibi M, Suzuki T. 2004. The Cerberus/ Dan-family protein Charon is a negative regulator of Nodal signaling during left-right patterning in zebrafish. Development 131: 1741-1753.
81. Hausler KD, Horwood NJ, Chuman Y, Fisher JL, Ellis J, Martin TJ, Rubin JS, Gillespie MT. 2004. Secreted frizzled-related protein-1 inhibits RANKL-dependent osteoclast formation. J Bone Miner Res 19: 1873-1881.
82. Hedge TA, Mason I. 2008. Expression of Shisa2, a modulator of both Wnt and Fgf signaling, in the chick embryo. Int J Dev Biol 52: 81-85.
83. Hoang B, Moos M Jr, Vukicevic S, Luyten FP. 1996. Primary structure and tissue distribution of FRZB, a novel protein related to Drosophila Frizzled, suggest a role in skeletal morphogenesis. J Biol Chem 271: 26131-26137.
84. Houart C, Caneparo L, Heisenberg C, Barth K, Take-Uchi M, Wilson S. 2002. Establishment of the telencephalon during gastrulation by local antagonism of Wnt signaling. Neuron 35: 255-265.
85. Hsieh JC, Kodjabachian L, Rebbert ML, Rattner A, Smallwood PM, Samos CH, Nusse R, Dawid IB, Nathans J. 1999. A new secreted protein that binds to Wnt proteins and inhibits their activities. Nature 398: 431-436.
86. Hu YA, Gu X, Liu J, Yang Y, Yan Y, Zhao C. 2008. Expression pattern of Wnt inhibitor factor 1 (Wif1) during the development in mouse CNS. Gene Expr Patterns 8: 515-522.
87. Hunter DD, Zhang M, Ferguson JW, Koch M, Brunken WJ. 2004. The extracellular matrix component WIF-1 is expressed during, and can modulate, retinal development. Mol Cell Neurosci 27: 477-488.
88. Idkowiak J, Weisheit G, Plitzner J, Viebahn C. 2004. Hypoblast controls mesoderm generation and axial patterning in the gastrulating rabbit embryo. Dev Genes Evol 214: 591-605.
89. Ishii Y, Wajid M, Bazzi H, Fantauzzo KA, Barber AG, Blaydon DC, Nam JS, Yoon JK, Kelsell DP, Christiano AM. 2008. Mutations in R-spondin 4 (RSPO4) underlie inherited anonychia. J Invest Dermatol 128: 867-870.
90. Itasaki N, Jones CM, Mercurio S, Rowe A, Domingos PM, Smith JC, Krumlauf R. 2003. Wise, a context-dependent activator and inhibitor of Wnt signalling. Development 130: 4295-4305.
91. Jin YR, Turcotte TJ, Crocker AL, Han XH, Yoon JK. 2011. The canonical Wnt signaling activator, R-spondin2, regulates craniofacial patterning and morphogenesis within the branchial arch through ectodermal-mesenchymal interaction. Dev Biol 352: 1-13.
92. Jones SE, Jomary C. 2002. Secreted Frizzled-related proteins: Searching for relationships and patterns. Bioessays 24: 811-820.
93. Jukkola T, Sinjushina N, Partanen J. 2004. Drapc1 expression during mouse embryonic development. Gene Expr Patterns 4: 755-762.
94. Junge HJ, Yang S, Burton JB, Paes K, Shu X, French DM, Costa M, Rice DS, Ye W. 2009. TSPAN12 regulates retinal vascular development by promoting Norrin- but not Wnt-induced FZD4/β-catenin signaling. Cell 139: 299-311.
95. Kagermeier-Schenk B, Wehner D, Ozhan-Kizil G, Yamamoto H, Li J, Kirchner K, Hoffmann C, Stern P, Kikuchi A, Schambony A, et al. 2011. Waif1/5T4 inhibits Wnt/β-catenin signaling and activates noncanonical Wnt pathways by modifying LRP6 subcellular localization. Dev Cell 21: 1129-1143.
96. Kamata T, Katsube K, Michikawa M, Yamada M, Takada S, Mizusawa H. 2004. R-spondin, a novel gene with thrombospondin type 1 domain, was expressed in the dorsal neural tube and affected in Wnts mutants. Biochim Biophys Acta 1676: 51-62.
97. Kaneko KJ, DePamphilis ML. 2000. Soggy, a spermatocytespecific gene, lies 3.8 kb upstream of and antipodal to TEAD-2, a transcription factor expressed at the beginning of mouse development. Nucleic Acids Res 28: 3982-3990.
98. Kansara M, Tsang M, Kodjabachian L, Sims NA, Trivett MK, Ehrich M, Dobrovic A, Slavin J, Choong PF, Simmons PJ, et al. 2009. Wnt inhibitory factor 1 is epigenetically silenced in human osteosarcoma, and targeted disruption accelerates osteosarcomagenesis in mice. J Clin Invest 119: 837-851.
99. Kassai Y, Munne P, Hotta Y, Penttila E, Kavanagh K, Ohbayashi N, Takada S, Thesleff I, Jernvall J, Itoh N. 2005. Regulation of mammalian tooth cusp patterning by ectodin. Science 309: 2067-2070.
100. Katoh Y, Katoh M. 2005. Comparative genomics on Shisa orthologs. Int J Mol Med 16: 181-185.
101. Kawano Y, Kypta R. 2003. Secreted antagonists of the Wnt signalling pathway. J Cell Sci 116: 2627-2634.
102. Kazanskaya O, Glinka A, Del Barco Barrantes I, Stannek P, Niehrs C, Wu W. 2004. R-Spondin2 is a secreted activator of Wnt/β-catenin signaling and is required for Xenopus myogenesis. Dev Cell 7: 525-534.
103. Kazanskaya O, Ohkawara B, Heroult M, Wu W, Maltry N, Augustin HG, Niehrs C. 2008. The Wnt signaling regulator R-spondin 3 promotes angioblast and vascular development. Development 135: 3655-3664.
104. Kelly OG, Pinson KI, Skarnes WC. 2004. The Wnt co-receptors Lrp5 and Lrp6 are essential for gastrulation in mice. Development 131: 2803-2815.
105. Kim KA, Kakitani M, Zhao J, Oshima T, Tang T, Binnerts M, Liu Y, Boyle B, Park E, Emtage P, et al. 2005. Mitogenic influence of human R-spondin1 on the intestinal epithelium. Science 309: 1256-1259.
106. Kim KA, Zhao J, Andarmani S, Kakitani M, Oshima T, Binnerts ME, Abo A, Tomizuka K, Funk WD. 2006. R-Spondin proteins: A novel link to β-catenin activation. Cell Cycle 5: 23-26.
107. Kim KA, Wagle M, Tran K, Zhan X, Dixon MA, Liu S, Gros D, Korver W, Yonkovich S, Tomasevic N, et al. 2008. R-Spondin family members regulate the Wnt pathway by a common mechanism. Mol Biol Cell 19: 2588-2596.
108. Kimura-Yoshida C, Nakano H, Okamura D, Nakao K, Yonemura S, Belo JA, Aizawa S, Matsui Y, Matsuo I. 2005. Canonical Wnt signaling and its antagonist regulate anterior-posterior axis polarization by guiding cell migration in mouse visceral endoderm. Dev Cell 9: 639-650.
109. Kohn MJ, Kaneko KJ, DePamphilis ML. 2005. DkkL1 (Soggy), a Dickkopf family member, localizes to the acrosome during mammalian spermatogenesis. Mol Reprod Dev 71: 516-522.
110. Krishnan V, Bryant HU, Macdougald OA. 2006. Regulation of bone mass by Wnt signaling. J Clin Invest 116: 1202-1209.
111. Krupnik VE, Sharp JD, Jiang C, Robison K, Chickering TW, Amaravadi L, Brown DE, Guyot D, Mays G, Leiby K, et al. 1999. Functional and structural diversity of the human Dickkopf gene family. Gene 238: 301-313.
112. Kuang SQ, Tong WG, Yang H, Lin W, Lee MK, Fang ZH, Wei Y, Jelinek J, Issa JP, Garcia-Manero G. 2008. Genomewide identification of aberrantly methylated promoter associated CpG islands in acute lymphocytic leukemia. Leukemia 22: 1529-1538.
113. Kuroda H, Wessely O, De Robertis EM. 2004. Neural induction in Xenopus: requirement for ectodermal and endomesodermal signals via Chordin, Noggin, β-Catenin, and Cerberus. PLoS Biol 2: E92.
114. Laurikkala J, Kassai Y, Pakkasjarvi L, Thesleff I, Itoh N. 2003. Identification of a secreted BMP antagonist, ectodin, integrating BMP, FGF, and SHH signals from the tooth enamel knot. Dev Biol 264: 91-105.
115. Leaf I, Tennessen J, Mukhopadhyay M, Westphal H, Shawlot W. 2006. Sfrp5 is not essential for axis formation in the mouse. Genesis 44: 573-578.
116. Lee CS, Buttitta LA, May NR, Kispert A, Fan CM. 2000. SHH-N upregulates Sfrp2 to mediate its competitive interaction with WNT1 and WNT4 in the somitic mesoderm. Development 127: 109-118.
117. Lee HX, Ambrosio AL, Reversade B, De Robertis EM. 2006. Embryonic dorsal-ventral signaling: Secreted frizzled-related proteins as inhibitors of tolloid proteinases. Cell 124: 147-159.
118. Lewiecki EM. 2011. Sclerostin monoclonal antibody therapy with AMG 785: A potential treatment for osteoporosis. Expert Opin Biol Ther 11: 117-127.
119. Leyns L, Bouwmeester T, Kim SH, Piccolo S, De Robertis EM. 1997. Frzb-1 is a secreted antagonist of Wnt signaling expressed in the Spemann organizer. Cell 88: 747-756.
120. Li L, Mao J, Sun L, Liu W, Wu D. 2002. Second cysteine-rich domain of Dickkopf-2 activates canonical Wnt signaling pathway via LRP-6 independently of Dishevelled. J Biol Chem 277: 5977-5981.
121. Li X, Liu P, Liu W, Maye P, Zhang J, Zhang Y, Hurley M, Guo C, Boskey A, Sun L, et al. 2005a. Dkk2 has a role in terminal osteoblast differentiation and mineralized matrix formation. Nat Genet 37: 945-952.
122. Li X, Zhang Y, Kang H, Liu W, Liu P, Zhang J, Harris SE, Wu D. 2005b. Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem 280: 19883- 19887.
123. Li J, Sarosi I, Cattley RC, Pretorius J, Asuncion F, Grisanti M, Morony S, Adamu S, Geng Z, Qiu W, et al. 2006. Dkk1-mediated inhibition of Wnt signaling in bone results in osteopenia. Bone 39: 754-766.
124. Li X, Ominsky MS, Niu QT, Sun N, Daugherty B, D'Agostin D, Kurahara C, Gao Y, Cao J, Gong J, et al. 2008a. Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res 23: 860-869.
125. Li Y, Rankin SA, Sinner D, Kenny AP, Krieg PA, Zorn AM. 2008b. Sfrp5 coordinates foregut specification and morphogenesis by antagonizing both canonical and noncanonical Wnt11 signaling. Genes Dev 22: 3050-3063.
126. Li Y, Pawlik B, Elcioglu N, Aglan M, Kayserili H, Yigit G, Percin F, Goodman F, Nurnberg G, Cenani A, et al. 2010. LRP4 mutations alter Wnt/β-catenin signaling and cause limb and kidney malformations in Cenani-Lenz syndrome. Am J Hum Genet 86: 696-706.
127. Li S, Esterberg R, Lachance V, Ren D, Radde-Gallwitz K, Chi F, Parent JL, Fritz A, Chen P. 2011. Rack1 is required for Vangl2 membrane localization and planar cell polarity signaling while attenuating canonical Wnt activity. Proc Natl Acad Sci 108: 2264-2269.
128. Lin K, Wang S, Julius MA, Kitajewski J, Moos MJ, Luyten FP. 1997. The cysteine-rich frizzled domain of Frzb-1 is required and sufficient for modulation of Wnt signaling. Proc Natl Acad Sci 94: 11196-11200.
129. Lintern KB, Guidato S, Rowe A, Saldanha JW, Itasaki N. 2009. Characterization of Wise protein and its molecular mechanism to interact with both Wnt and BMP signals. J Biol Chem 284: 23159-23168.
130. Little RD, Carulli JP, Del Mastro RG, Dupuis J, Osborne M, Folz C, Manning SP, Swain PM, Zhao SC, Eustace B, et al. 2002. A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait. Am J Hum Genet 70: 11-19.
131. Lopez-Rios J, Esteve P, Ruiz JM, Bovolenta P. 2008. The Netrin-related domain of Sfrp1 interacts with Wnt ligands and antagonizes their activity in the anterior neural plate. Neural Dev 3: 19.
132. Lowther W, Wiley K, Smith GH, Callahan R. 2005. A new common integration site, Int7, for the mouse mammary tumor virus in mouse mammary tumors identifies a gene whose product has furin-like and thrombospondin-like sequences. J Virol 79: 10093-10096.
133. Luhmann UF, Lin J, Acar N, Lammel S, Feil S, Grimm C, Seeliger MW, Hammes HP, Berger W. 2005a. Role of the Norrie disease pseudoglioma gene in sprouting angiogenesis during development of the retinal vasculature. Invest Ophthalmol Vis Sci 46: 3372-3382.
134. Luhmann UF, Meunier D, Shi W, Luttges A, Pfarrer C, Fundele R, Berger W. 2005b. Fetal loss in homozygous mutant Norrie disease mice: A new role of Norrin in reproduction. Genesis 42: 253-262.
135. Luke GN, Castro LF, McLay K, Bird C, Coulson A, Holland PW. 2003. Dispersal of NK homeobox gene clusters in amphioxus and humans. Proc Natl Acad Sci 100: 5292-5295.
136. MacDonald BT, Adamska M, Meisler MH. 2004. Hypomorphic expression of Dkk1 in the doubleridge mouse: Dose dependence and compensatory interactions with Lrp6. Development 131: 2543-2552.
137. MacDonald BT, Joiner DM, Oyserman SM, Sharma P, Goldstein SA, He X, Hauschka PV. 2007. Bone mass is inversely proportional to Dkk1 levels in mice. Bone 41: 331-339.
138. Mao B, Niehrs C. 2003. Kremen2 modulates Dickkopf2 activity during Wnt/LRP6 signaling. Gene 302: 179-183.
139. Mao B, Wu W, Li Y, Hoppe D, Stannek P, Glinka A, Niehrs C. 2001. LDL-receptor-related protein 6 is a receptor for Dickkopf proteins. Nature 411: 321-325.
140. Mao B, Wu W, Davidson G, Marhold J, Li M, Mechler B, Delius H, Hoppe D, Stannek P, et al. 2002. Kremens are novel Dickkopf receptors that regulate Wnt/β-catenin signalling. Nature 417: 664-667.
141. Marques S, Borges AC, Silva AC, Freitas S, Cordenonsi M, Belo JA. 2004. The activity of the Nodal antagonist Cerl-2 in the mouse node is required for correct L/R body axis. Genes Dev 18: 2342-2347.
142. Matsuyama M, Aizawa S, Shimono A. 2009. Sfrp controls apicobasal polarity and oriented cell division in developing gut epithelium. PLoS Genet 5: e1000427.
143. Meindl A, Berger W, Meitinger T, van de Pol D, Achatz H, Dorner C, Haasemann M, Hellebrand H, Gal A, Cremers F, et al. 1992. Norrie disease is caused by mutations in an extracellular protein resembling C-terminal globular domain of mucins. Nat Genet 2: 139-143.
144. Meitinger T, Meindl A, Bork P, Rost B, Sander C, Haasemann M, Murken J. 1993. Molecular modelling of the Norrie disease protein predicts a cystine knot growth factor tertiary structure. Nat Genet 5: 376-380.
145. Melkonyan HS, Chang WC, Shapiro JP, Mahadevappa M, Fitzpatrick PA, Kiefer MC, Tomei LD, Umansky SR. 1997. SARPs: A family of secreted apoptosis-related proteins. Proc Natl Acad Sci 94: 13636-13641.
146. Mii Y, Taira M. 2009. Secreted Frizzled-related proteins enhance the diffusion of Wnt ligands and expand their signalling range. Development 136: 4083-4088.
147. Monaghan AP, Kioschis P, Wu W, Zuniga A, Bock D, Poustka A, Delius H, Niehrs C. 1999. Dickkopf genes are co-ordinately expressed in mesodermal lineages. Mech Dev 87: 45-56.
148. Morvan F, Boulukos K, Clement-Lacroix P, Roman Roman S, Suc-Royer I, Vayssiere B, Ammann P, Martin P, Pinho S, Pognonec P, et al. 2006. Deletion of a single allele of the Dkk1 gene leads to an increase in bone formation and bone mass. J Bone Miner Res 21: 934-945.
149. Mukhopadhyay M, Shtrom S, Rodriguez-Esteban C, Chen L, Tsukui T, Gomer L, Dorward DW, Glinka A, Grinberg A, Huang SP, et al. 2001. Dickkopf1 is required for embryonic head induction and limb morphogenesis in the mouse. Dev Cell 1: 423-434.
150. Mukhopadhyay M, Gorivodsky M, Shtrom S, Grinberg A, Niehrs C, Morasso MI, Westphal H. 2006. Dkk2 plays an essential role in the corneal fate of the ocular surface epithelium. Development 133: 2149-2154.
151. Nagano T, Takehara S, Takahashi M, Aizawa S, Yamamoto A. 2006. Shisa2 promotes the maturation of somitic precur sors and transition to the segmental fate in Xenopus embryos. Development 133: 4643-4654.
152. Naganuma H, Kono K, Mori Y, Takayoshi S, Stern PL, Tasaka K, Matsumoto Y. 2002. Oncofetal antigen 5T4 expression as a prognostic factor in patients with gastric cancer. Anticancer Res 22: 1033-1038.
153. Nam JS, Turcotte TJ, Smith PF, Choi S, Yoon JK. 2006. Mouse cristin/R-spondin family proteins are novel ligands for the Frizzled 8 and LRP6 receptors and activate β-catenin-dependent gene expression. J Biol Chem 281: 13247-13257.
154. Nam JS, Park E, Turcotte TJ, Palencia S, Zhan X, Lee J, Yun K, Funk WD, Yoon JK. 2007a. Mouse R-spondin2 is required for apical ectodermal ridge maintenance in the hindlimb. Dev Biol 311: 124-135.
155. Nam JS, Turcotte TJ, Yoon JK. 2007b. Dynamic expression of R-spondin family genes in mouse development. Gene Expr Patterns 7: 306-312.
156. Nie X. 2005. Dkk1, -2, and -3 expression in mouse craniofacial development. J Mol Histol 36: 367-372.
157. Nie X, Luukko K, Fjeld K, Kvinnsland IH, Kettunen P. 2005. Developmental expression of Dkk1-3 and Mmp9 and apoptosis in cranial base of mice. J Mol Histol 36: 419-426.
158. Niehrs C. 2004. Regionally specific induction by the Spemann-Mangold organizer. Nat Rev Genet 5: 425-434.
159. Niehrs C. 2006. Function and biological roles of the Dickkopf family of Wnt modulators. Oncogene 25: 7469- 7481.
160. Niehrs C. 2010. On growth and form: A Cartesian coordinate system of Wnt and BMP signaling specifies bilaterian body axes. Development 137: 845-857.
161. Ning Y, Schuller AG, Bradshaw S, Rotwein P, Ludwig T, Frystyk J, Pintar JE. 2006. Diminished growth and enhanced glucose metabolism in triple knockout mice containing mutations of insulin-like growth factor binding protein-3, -4, and -5. Mol Endocrinol 20: 2173-2186.
162. Ohazama A, Johnson EB, Ota MS, Choi HY, Porntaveetus T, Oommen S, Itoh N, Eto K, Gritli-Linde A, Herz J, et al. 2008. Lrp4 modulates extracellular integration of cell signaling pathways in development. PLoS ONE 3: e4092.
163. Ohkawara B, Glinka A, Niehrs C. 2011. Rspo3 binds syndecan 4 and induces Wnt/PCP signaling via clathrin-mediated endocytosis to promote morphogenesis. Dev Cell 20: 303-314.
164. Ootani A, Li X, Sangiorgi E, Ho QT, Ueno H, Toda S, Sugihara H, Fujimoto K, Weissman IL, Capecchi MR, et al. 2009. Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell niche. Nat Med 15: 701-706.
165. O'Shaughnessy RF, Yeo W, Gautier J, Jahoda CA, Christiano AM. 2004. The WNT signalling modulator, Wise, is expressed in an interaction-dependent manner during hair-follicle cycling. J Invest Dermatol 123: 613-621.
166. Padhi D, Jang G, Stouch B, Fang L, Posvar E. 2011. Singledose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res 26: 19-26.
167. Parma P, Radi O, Vidal V, Chaboissier MC, Dellambra E, Valentini S, Guerra L, Schedl A, Camerino G. 2006. R- Spondin1 is essential in sex determination, skin differentiation and malignancy. Nat Genet 38: 1304-1309.
168. Pei J, Grishin NV. 2012. Unexpected diversity in Shisa-like proteins suggests the importance of their roles as transmembrane adaptors. Cell Signal 24: 758-769.
169. Pera EM, De Robertis EM. 2000. A direct screen for secreted proteins in Xenopus embryos identifies distinct activities for the Wnt antagonists Crescent and Frzb-1. Mech Dev 96: 183-195.
170. Pfeffer PL, De Robertis EM, Izpisua-Belmonte JC. 1997. Crescent, a novel chick gene encoding a Frizzled-like cysteine-rich domain, is expressed in anterior regions during early embryogenesis. Int J Dev Biol 41: 449-458.
171. Piccolo S, Agius E, Leyns L, Bhattacharyya S, Grunz H, Bouwmeester T, De Robertis EM. 1999. The head inducer Cerberus is a multifunctional antagonist of Nodal, BMP and Wnt signals. Nature 397: 707-710.
172. Pinho S, Niehrs C. 2007. Dkk3 is required for TGF-β signaling during Xenopus mesoderm induction. Differentiation 75: 957-967.
173. Pollard SL, Holland PW. 2000. Evidence for 14 homeobox gene clusters in human genome ancestry. Curr Biol 10: 1059-1062.
174. Rattner A, Hsieh J-C, Smallwood PM, Gilbert D, Copeland NG, Jenkins NA, Nathans J. 1997. A family of secreted proteins contains homology to the cysteine-rich ligand binding domain of frizzled receptors. Proc Natl Acad Sci 94: 2859-2863.
175. Rehm HL, Zhang DS, Brown MC, Burgess B, Halpin C, Berger W, Morton CC, Corey DP, Chen ZY. 2002. Vascular defects and sensorineural deafness in a mouse model of Norrie disease. J Neurosci 22: 4286-4292.
176. Rehn M, Pihlajaniemi T, Hofmann K, Bucher P. 1998. The frizzled motif: In how many different protein families does it occur? Trends Biochem Sci 23: 415-417.
177. Richter M, Gottanka J, May CA, Welge-Lussen U, Berger W, Lutjen-Drecoll E. 1998. Retinal vasculature changes in Norrie disease mice. Invest Ophthalmol Vis Sci 39: 2450-2457.
178. Robitaille J, MacDonald ML, Kaykas A, Sheldahl LC, Zeisler J, Dube MP, Zhang LH, Singaraja RR, Guernsey DL, Zheng B, et al. 2002. Mutant frizzled-4 disrupts retinal angiogenesis in familial exudative vitreoretinopathy. Nat Genet 32: 326-330.
179. Rodriguez Esteban C, Capdevila J, Economides AN, Pascual J, Ortiz A, Izpisua Belmonte JC. 1999. The novel Cer-like protein Caronte mediates the establishment of embryonic left-right asymmetry. Nature 401: 243-251.
180. Rodriguez J, Esteve P, Weinl C, Ruiz JM, Fermin Y, Trousse F, Dwivedy A, Holt C, Bovolenta P. 2005. SFRP1 regulates the growth of retinal ganglion cell axons through the Fz2 receptor. Nat Neurosci 8: 1301-1309.
181. Salic AN, Kroll KL, Evans LM, Kirschner MW. 1997. Sizzled: A secreted Xwnt8 antagonist expressed in the ventral marginal zone of Xenopus embryos. Development 124: 4739-4748.
182. Sato H, Suzuki H, Toyota M, Nojima M, Maruyama R, Sasaki S, Takagi H, Sogabe Y, Sasaki Y, Idogawa M, et al. 2007. Frequent epigenetic inactivation of DICKKOPF family genes in human gastrointestinal tumors. Carcinogenesis 28: 2459-2466.
183. Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, van Es JH, Abo A, Kujala P, Peters PJ, et al. 2009. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459: 262-265.
184. Satoh W, Gotoh T, Tsunematsu Y, Aizawa S, Shimono A. 2006. Sfrp1 and Sfrp2 regulate anteroposterior axis elongation and somite segmentation during mouse embryogenesis. Development 133: 989-999.
185. Satoh W, Matsuyama M, Takemura H, Aizawa S, Shimono A. 2008. Sfrp1, Sfrp2, and Sfrp5 regulate the Wnt/β-catenin and the planar cell polarity pathways during early trunk formation in mouse. Genesis 46: 92-103.
186. Schneider VA, Mercola M. 2001. Wnt antagonism initiates cardiogenesis in Xenopus laevis. Genes Dev 15: 304-315.
187. Schwarz-Romond T, Asbrand C, Bakkers J, Kuhl M, Schaeffer HJ, Huelsken J, Behrens J, Hammerschmidt M, Birchmeier W. 2002. The ankyrin repeat protein Diversin recruits Casein kinase Iε to the β-catenin degradation complex and acts in both canonical Wnt and Wnt/JNK signaling. Genes Dev 16: 2073-2084.
188. Semenov MV, He X. 2006. LRP5 mutations linked to high bone mass diseases cause reduced LRP5 binding and inhibition by SOST. J Biol Chem 281: 38276-38284.
189. Semenov MV, Tamai K, Brott BK, Kuhl M, Sokol S, He X. 2001. Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6. Curr Biol 11: 951-961.
190. Semenov M, Tamai K, He X. 2005. SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor. J Biol Chem 280: 26770-26775.
191. Semenov MV, Zhang X, He X. 2008. DKK1 antagonizes Wnt signaling without promotion of LRP6 internalization and degradation. J Biol Chem 283: 21427-21432.
192. Shawlot W, Min Deng J, Wakamiya M, Behringer RR. 2000. The cerberus-related gene, Cerr1, is not essential for mouse head formation. Genesis 26: 253-258.
193. Shimomura Y, Agalliu D, Vonica A, Luria V, Wajid M, Baumer A, Belli S, Petukhova L, Schinzel A, Brivanlou AH, et al. 2010. APCDD1 is a novel Wnt inhibitor mutated in hereditary hypotrichosis simplex. Nature 464: 1043-1047.
194. Shinya M, Eschbach C, Clark M, Lehrach H, Furutani- Seiki M. 2000. Zebrafish Dkk1, induced by the pre-MBT Wnt signaling, is secreted from the prechordal plate and patterns the anterior neural plate. Mech Dev 98: 3-17.
195. Silva AC, Filipe M, Kuerner KM, Steinbeisser H, Belo JA. 2003. Endogenous Cerberus activity is required for anterior head specification in Xenopus. Development 130: 4943-4953.
196. Silva AC, Filipe M, Vitorino M, Steinbeisser H, Belo JA. 2006. Developmental expression of Shisa-2 in Xenopus laevis. Int J Dev Biol 50: 575-579.
197. Simons M, Gloy J, Ganner A, Bullerkotte A, Bashkurov M, Kronig C, Schermer B, Benzing T, Cabello OA, Jenny A, et al. 2005. Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways. Nat Genet 37: 537-543.
198. Simpson EH, Johnson DK, Hunsicker P, Suffolk R, Jordan SA, Jackson IJ. 1999. The mouse Cer1 (Cerberus related or homologue) gene is not required for anterior pattern formation. Dev Biol 213: 202-206.
199. Smallwood PM, Williams J, Xu Q, Leahy DJ, Nathans J. 2007. Mutational analysis of Norrin-Frizzled4 recognition. J Biol Chem 282: 4057-4068.
200. Soshnikova N, Zechner D, Huelsken J, Mishina Y, Behringer RR, Taketo MM, Crenshaw EB III, Birchmeier W. 2003. Genetic interaction between Wnt/β-catenin and BMP receptor signaling during formation of the AER and the dorsal-ventral axis in the limb. Genes Dev 17: 1963-1968.
201. Southgate TD, McGinn OJ, Castro FV, Rutkowski AJ, Al-Muftah M, Marinov G, Smethurst GJ, Shaw D, Ward CM, Miller CJ, et al. 2010. CXCR4 mediated chemotaxis is regulated by 5T4 oncofetal glycoprotein in mouse embryonic cells. PLoS ONE 5: e9982.
202. Staehling-Hampton K, Proll S, Paeper BW, Zhao L, Charmley P, Brown A, Gardner JC, Galas D, Schatzman RC, Beighton P, et al. 2002. A 52-kb deletion in the SOST-MEOX1 intergenic region on 17q12-q21 is associated with van Buchem disease in the Dutch population. Am J Med Genet 110: 144-152.
203. Stanley EG, Biben C, Allison J, Hartley L, Wicks IP, Campbell IK, McKinley M, Barnett L, Koentgen F, Robb L, et al. 2000. Targeted insertion of a lacZ reporter gene into the mouse Cer1 locus reveals complex and dynamic expression during embryogenesis. Genesis 26: 259-264.
204. Starr TK, Allaei R, Silverstein KA, Staggs RA, Sarver AL, Bergemann TL, Gupta M, O'Sullivan MG, Matise I, Dupuy AJ, et al. 2009. A transposon-based genetic screen in mice identifies genes altered in colorectal cancer. Science 323: 1747-1750.
205. Starzynska T, Marsh PJ, Schofield PF, Roberts SA, Myers KA, Stern PL. 1994. Prognostic significance of 5T4 oncofetal antigen expression in colorectal carcinoma. Br J Cancer 69: 899-902.
206. Sugiyama Y, Stump RJ, Nguyen A, Wen L, Chen Y, Wang Y, Murdoch JN, Lovicu FJ, McAvoy JW. 2010. Secreted frizzled-related protein disrupts PCP in eye lens fiber cells that have polarised primary cilia. Dev Biol 338: 193-201.
207. Surmann-Schmitt C, Widmann N, Dietz U, Saeger B, Eitzinger N, Nakamura Y, Rattel M, Latham R, Hartmann C, von der Mark H, et al. 2009. Wif-1 is expressed at cartilage-mesenchyme interfaces and impedes Wnt3a-mediated inhibition of chondrogenesis. J Cell Sci 122: 3627-3637.
208. Swain RK, Katoh M, Medina A, Steinbeisser H. 2005. Xenopus frizzled-4S, a splicing variant of Xfz4 is a contextdependent activator and inhibitor of Wnt/β-catenin signaling. Cell Commun Signal 3: 12.
209. Takahashi M, Fujita M, Furukawa Y, Hamamoto R, Shimokawa T, Miwa N, Ogawa M, Nakamura Y. 2002. Isolation of a novel human gene, APCDD1, as a direct target of the β-catenin/T-cell factor 4 complex with probable involvement in colorectal carcinogenesis. Cancer Res 62: 5651-5656.
210. Tavares AT, Andrade S, Silva AC, Belo JA. 2007. Cerberus is a feedback inhibitor of Nodal asymmetric signaling in the chick embryo. Development 134: 2051-2060.
211. Theodorou V, Kimm MA, Boer M, Wessels L, Theelen W, Jonkers J, Hilkens J. 2007. MMTV insertional mutagen esis identifies genes, gene families and pathways involved in mammary cancer. Nat Genet 39: 759-769.
212. Tomaselli S, Megiorni F, De Bernardo C, Felici A, Marrocco G, Maggiulli G, Grammatico B, Remotti D, Saccucci P, Valentini F, et al. 2008. Syndromic true hermaphroditism due to an R-spondin1 (RSPO1) homozygous mutation. Hum Mutat 29: 220-226.
213. Tomizuka K, Horikoshi K, Kitada R, Sugawara Y, Iba Y, Kojima A, Yoshitome A, Yamawaki K, Amagai M, Inoue A, et al. 2008. R-Spondin1 plays an essential role in ovarian development through positively regulating Wnt-4 signaling. Hum Mol Genet 17: 1278-1291.
214. Toomes C, Bottomley HM, Jackson RM, Towns KV, Scott S, Mackey DA, Craig JE, Jiang L, Yang Z, Trembath R, et al. 2004a. Mutations in LRP5 or FZD4 underlie the common familial exudative vitreoretinopathy locus on chromosome 11q. Am J Hum Genet 74: 721-730.
215. Toomes C, Bottomley HM, Scott S, Mackey DA, Craig JE, Appukuttan B, Stout JT, Flaxel CJ, Zhang K, Black GC, et al. 2004b. Spectrum and frequency of FZD4 mutations in familial exudative vitreoretinopathy. Invest Ophthalmol Vis Sci 45: 2083-2090.
216. Uren A, Reichsman F, Anest V, Taylor WG, Muraiso K, Bottaro DP, Cumberledge S, Rubin JS. 2000. Secreted frizzled-related protein-1 binds directly to Wingless and is a biphasic modulator of Wnt signaling. J Biol Chem 275: 4374-4382.
217. Vainio S, Heikkila M, Kispert A, Chin N, McMahon AP. 1999. Female development in mammals is regulated by Wnt-4 signalling. Nature 397: 405-409.
218. Vonica A, Brivanlou AH. 2007. The left-right axis is regulated by the interplay of Coco, Xnr1 and derrière in Xenopus embryos. Dev Biol 303: 281-294.
219. Wang S, Krinks M, Lin K, Luyten FP, Moos M Jr. 1997. Frzb, a secreted protein expressed in the Spemann organizer, binds and inhibits Wnt-8. Cell 88: 757-766.
220. Wang K, Zhang Y, Li X, Chen L, Wang H, Wu J, Zheng J, Wu D. 2008. Characterization of the Kremen-binding site on Dkk1 and elucidation of the role of Kremen in Dkk-mediated Wnt antagonism. J Biol Chem 283: 23371-23375.
221. Warden SM, Andreoli CM, Mukai S. 2007. The Wnt signaling pathway in familial exudative vitreoretinopathy and Norrie disease. Semin Ophthalmol 22: 211-217.
222. Warr N, Siggers P, Bogani D, Brixey R, Pastorelli L, Yates L, Dean CH, Wells S, Satoh W, Shimono A, et al. 2009. Sfrp1 and Sfrp2 are required for normal male sexual development in mice. Dev Biol 326: 273-284.
223. Wawrzak D, Metioui M, Willems E, Hendrickx M, de Genst E, Leyns L. 2007. Wnt3a binds to several sFRPs in the nanomolar range. Biochem Biophys Res Commun 357: 1119-1123.
224. Wei Q, Yokota C, Semenov MV, Doble B, Woodgett J, He X. 2007. R-Spondin1 is a high affinity ligand for LRP6 and induces LRP6 phosphorylation and β-catenin signaling. J Biol Chem 282: 15903-15911.
225. Winkler DG, Sutherland MK, Geoghegan JC, Yu C, Hayes T, Skonier JE, Shpektor D, Jonas M, Kovacevich BR, Staehling-Hampton K, et al. 2003. Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. EMBO J 22: 6267-6276.
226. Wu W, Glinka A, Delius H, Niehrs C. 2000. Mutual antagonism between dickkopf1 and dickkopf2 regulates Wnt/βcatenin signalling. Curr Biol 10: 1611-1614.
227. Xia CH, Liu H, Cheung D, Wang M, Cheng C, Du X, Chang B, Beutler B, Gong X. 2008. A model for familial exudative vitreoretinopathy caused by LPR5 mutations. Hum Mol Genet 17: 1605-1612.
228. Xu Q, Wang Y, Dabdoub A, Smallwood PM, Williams J, Woods C, Kelley MW, Jiang L, Tasman W, Zhang K, et al. 2004. Vascular development in the retina and inner ear: Control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair. Cell 116: 883-895.
229. Yamada W, Nagao K, Horikoshi K, Fujikura A, Ikeda E, Inagaki Y, Kakitani M, Tomizuka K, Miyazaki H, Suda T, et al. 2009. Craniofacial malformation in R-spondin2 knockout mice. Biochem Biophys Res Commun 381: 453-458.
230. Yamamoto A, Nagano T, Takehara S, Hibi M, Aizawa S. 2005. Shisa promotes head formation through the inhibition of receptor protein maturation for the caudalizing factors, Wnt and FGF. Cell 120: 223-235.
231. Yan D, Wallingford JB, Sun TQ, Nelson AM, Sakanaka C, Reinhard C, Harland RM, Fantl WJ, Williams LT. 2001. Cell autonomous regulation of multiple Dishevelled-dependent pathways by mammalian Nkd. Proc Natl Acad Sci 98: 3802-3807.
232. Yanagita M, Oka M, Watabe T, Iguchi H, Niida A, Takahashi S, Akiyama T, Miyazono K, Yanagisawa M, Sakurai T. 2004. USAG-1: A bone morphogenetic protein antagonist abundantly expressed in the kidney. Biochem Biophys Res Commun 316: 490-500.
233. Yanagita M, Okuda T, Endo S, Tanaka M, Takahashi K, Sugiyama F, Kunita S, Takahashi S, Fukatsu A, Yanagisawa M, et al. 2006. Uterine sensitization-associated gene-1 (USAG-1), a novel BMP antagonist expressed in the kidney, accelerates tubular injury. J Clin Invest 116: 70-79.
234. Ye X, Smallwood P, Nathans J. 2011. Expression of the Norrie disease gene (Ndp) in developing and adult mouse eye, ear, and brain. Gene Expr Patterns 11: 151-155.
235. Yokouchi Y, Vogan KJ, Pearse RV II, Tabin CJ. 1999. Antagonistic signaling by Caronte, a novel Cerberus-related gene, establishes left-right asymmetric gene expression. Cell 98: 573-583.
236. Yoon JK, Lee JS. 2012. Cellular signaling and biological functions of R-spondins. Cell Signal 24: 369-377.
237. Zhang X, Abreu JG, Yokota C, Macdonald BT, Singh S, Coburn KL, Cheong SM, Zhang MM, Ye QZ, Hang HC, et al. 2012. tiki1 is required for head formation via Wnt cleavage-oxidation and inactivation. Cell 149: 1565-1577.
238. Zhu L, Marvin MJ, Gardiner A, Lassar AB, Mercola M, Stern CD, Levin M. 1999. Cerberus regulates left-right asymmetry of the embryonic head and heart. Curr Biol 9: 931-938.
239. Zhu W, Shiojima I, Ito Y, Li Z, Ikeda H, Yoshida M, Naito AT, Nishi J, Ueno H, Umezawa A, et al. 2008a. IGFBP-4 is an inhibitor of canonical Wnt signalling required for cardiogenesis. Nature 454: 345-349.
240. Zhu Y, Tsuchida A, Yamamoto A, Furukawa K, Tajima O, Tokuda N, Aizawa S, Urano T, Kadomatsu K. 2008b. Expression and roles of a Xenopus head-forming gene homologue in human cancer cell lines. Nagoya J Med Sci 70: 73-82.