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Cell and Tissue Research

, Volume 331, Issue 1, pp 193–210 | Cite as

Wnt signaling and neural stem cells: caught in the Wnt web

  • Theologos M. Michaelidis
  • D. Chichung LieEmail author
Review

Abstract

Wnt proteins have now been identified as major physiological regulators of multiple aspects of stem cell biology, from self-renewal and pluripotency to precursor cell competence and terminal differentiation. Neural stem cells are the cellular building blocks of the developing nervous system and provide the basis for continued neurogenesis in the adult mammalian central nervous system. Here, we outline the most recent advances in the field about the critical factors and regulatory networks involved in Wnt signaling and discuss recent findings on how this increasingly intricate pathway contributes to the shaping of the developing and adult nervous system on the level of the neural stem cell.

Keywords

Signaling Wnt Stem cell Neurogenesis Development 

References

  1. Arce L, Yokoyama NN, Waterman ML (2006) Diversity of LEF/TCF action in development and disease. Oncogene 25:7492–7504PubMedGoogle Scholar
  2. Arvidsson A, Kokaia Z, Lindvall O (2001) N-methyl-D-aspartate receptor-mediated increase of neurogenesis in adult rat dentate gyrus following stroke. Eur J Neurosci 14:10–18PubMedGoogle Scholar
  3. Atcha FA, Munguia JE, Li TW, Hovanes K, Waterman ML (2003) A new beta-catenin-dependent activation domain in T cell factor. J Biol Chem 278:16169–16175PubMedGoogle Scholar
  4. Backman M, Machon O, Mygland L, van den Bout CJ, Zhong W, Taketo MM, Krauss S (2005) Effects of canonical Wnt signaling on dorso-ventral specification of the mouse telencephalon. Dev Biol 279:155–168PubMedGoogle Scholar
  5. Ballas N, Mandel G (2005) The many faces of REST oversee epigenetic programming of neuronal genes. Curr Opin Neurobiol 15:500–506PubMedGoogle Scholar
  6. Banziger C, Soldini D, Schutt C, Zipperlen P, Hausmann G, Basler K (2006) Wntless, a conserved membrane protein dedicated to the secretion of Wnt proteins from signaling cells. Cell 125:509–522PubMedGoogle Scholar
  7. Barolo S, Posakony JW (2002) Three habits of highly effective signaling pathways: principles of transcriptional control by developmental cell signaling. Genes Dev 16:1167–1181PubMedGoogle Scholar
  8. Bartscherer K, Pelte N, Ingelfinger D, Boutros M (2006) Secretion of Wnt ligands requires Evi, a conserved transmembrane protein. Cell 125:523–533PubMedGoogle Scholar
  9. Bejsovec A (2005) Wnt pathway activation: new relations and locations. Cell 120:11–14PubMedGoogle Scholar
  10. Beland M, Pilon N, Houle M, Oh K, Sylvestre JR, Prinos P, Lohnes D (2004) Cdx1 autoregulation is governed by a novel Cdx1-LEF1 transcription complex. Mol Cell Biol 24:5028–5038PubMedGoogle Scholar
  11. Bienz M (2002) The subcellular destinations of APC proteins. Nat Rev Mol Cell Biol 3:328–338PubMedGoogle Scholar
  12. Boras K, Hamel PA (2002) Alx4 binding to LEF-1 regulates N-CAM promoter activity. J Biol Chem 277:1120–1127PubMedGoogle Scholar
  13. Brembeck FH, Schwarz-Romond T, Bakkers J, Wilhelm S, Hammerschmidt M, Birchmeier W (2004) Essential role of BCL9-2 in the switch between beta-catenin’s adhesive and transcriptional functions. Genes Dev 18:2225–2230PubMedGoogle Scholar
  14. Briata P, Ilengo C, Corte G, Moroni C, Rosenfeld MG, Chen CY, Gherzi R (2003) The Wnt/beta-catenin-->Pitx2 pathway controls the turnover of Pitx2 and other unstable mRNAs. Mol Cell 12:1201–1211Google Scholar
  15. Brott BK, Sokol SY (2005) Frodo proteins: modulators of Wnt signaling in vertebrate development. Differentiation 73:323–329PubMedGoogle Scholar
  16. Calegari F, Haubensak W, Haffner C, Huttner WB (2005) Selective lengthening of the cell cycle in the neurogenic subpopulation of neural progenitor cells during mouse brain development. J Neurosci 25:6533–6538PubMedGoogle Scholar
  17. Cameron HA, McEwen BS, Gould E (1995) Regulation of adult neurogenesis by excitatory input and NMDA receptor activation in the dentate gyrus. J Neurosci 15:4687–4692PubMedGoogle Scholar
  18. Castelo-Branco G, Wagner J, Rodriguez FJ, Kele J, Sousa K, Rawal N, Pasolli HA, Fuchs E, Kitajewski J, Arenas E (2003) Differential regulation of midbrain dopaminergic neuron development by Wnt-1, Wnt-3a, and Wnt-5a. Proc Natl Acad Sci USA 100:12747–12752PubMedGoogle Scholar
  19. Castelo-Branco G, Sousa KM, Bryja V, Pinto L, Wagner J, Arenas E (2006) Ventral midbrain glia express region-specific transcription factors and regulate dopaminergic neurogenesis through Wnt-5a secretion. Mol Cell Neurosci 31:251–262PubMedGoogle Scholar
  20. Chen F, Rebay I (2000) split ends, a new component of the Drosophila EGF receptor pathway, regulates development of midline glial cells. Curr Biol 10:943–946PubMedGoogle Scholar
  21. Chen ZF, Paquette AJ, Anderson DJ (1998) NRSF/REST is required in vivo for repression of multiple neuronal target genes during embryogenesis. Nat Genet 20:136–142PubMedGoogle Scholar
  22. Chen J, Park CS, Tang SJ (2006) Activity-dependent synaptic WNT release regulates hippocampal long-term potentiation. J Biol ChemGoogle Scholar
  23. Chenn A, Walsh CA (2002) Regulation of cerebral cortical size by control of cell cycle exit in neural precursors. Science 297:365–369PubMedGoogle Scholar
  24. Cheyette BN (2004) Ryk: another heretical Wnt receptor defies the canon. Sci STKE 2004:pe54Google Scholar
  25. Chinnadurai G (2002) CtBP, an unconventional transcriptional corepressor in development and oncogenesis. Mol Cell 9:213–224PubMedGoogle Scholar
  26. Chizhikov VV, Millen KJ (2005) Roof plate-dependent patterning of the vertebrate dorsal central nervous system. Dev Biol 277:287–295PubMedGoogle Scholar
  27. Ciani L, Salinas PC (2005) WNTs in the vertebrate nervous system: from patterning to neuronal connectivity. Nat Rev Neurosci 6:351–362PubMedGoogle Scholar
  28. Clevers H (2006) Wnt/beta-catenin signaling in development and disease. Cell 127:469–480PubMedGoogle Scholar
  29. Coudreuse D, Korswagen HC (2007) The making of Wnt: new insights into Wnt maturation, sorting and secretion. Development 134:3–12PubMedGoogle Scholar
  30. Coudreuse DY, Roel G, Betist MC, Destree O, Korswagen HC (2006) Wnt gradient formation requires retromer function in Wnt-producing cells. Science 312:921–924PubMedGoogle Scholar
  31. Daniels DL, Weis WI (2005) Beta-catenin directly displaces Groucho/TLE repressors from Tcf/Lef in Wnt-mediated transcription activation. Nat Struct Mol Biol 12:364–371PubMedGoogle Scholar
  32. Das AV, Zhao X, James J, Kim M, Cowan KH, Ahmad I (2006) Neural stem cells in the adult ciliary epithelium express GFAP and are regulated by Wnt signaling. Biochem Biophys Res Commun 339:708–716PubMedGoogle Scholar
  33. DasGupta R, Fuchs E (1999) Multiple roles for activated LEF/TCF transcription complexes during hair follicle development and differentiation. Development 126:4557–4568PubMedGoogle Scholar
  34. Davidson G, Wu W, Shen J, Bilic J, Fenger U, Stannek P, Glinka A, Niehrs C (2005) Casein kinase 1 gamma couples Wnt receptor activation to cytoplasmic signal transduction. Nature 438:867–872PubMedGoogle Scholar
  35. Dorsky RI, Sheldahl LC, Moon RT (2002) A transgenic Lef1/beta-catenin-dependent reporter is expressed in spatially restricted domains throughout zebrafish development. Dev Biol 241:229–237PubMedGoogle Scholar
  36. Duncan AW, Rattis FM, DiMascio LN, Congdon KL, Pazianos G, Zhao C, Yoon K, Cook JM, Willert K, Gaiano N, Reya T (2005) Integration of Notch and Wnt signaling in hematopoietic stem cell maintenance. Nat Immunol 6:314–322PubMedGoogle Scholar
  37. Fan G, Martinowich K, Chin MH, He F, Fouse SD, Hutnick L, Hattori D, Ge W, Shen Y, Wu H, ten Hoeve J, Shuai K, Sun YE (2005) DNA methylation controls the timing of astrogliogenesis through regulation of JAK-STAT signaling. Development 132:3345–3356PubMedGoogle Scholar
  38. Fang M, Li J, Blauwkamp T, Bhambhani C, Campbell N, Cadigan KM (2006) C-terminal-binding protein directly activates and represses Wnt transcriptional targets in Drosophila. EMBO J 25:2735–2745PubMedGoogle Scholar
  39. Feng Y, Bommer GT, Zhai Y, Akyol A, Hinoi T, Winer I, Lin HV, Cadigan KM, Cho KR, Fearon ER (2007) Drosophila split ends homologue SHARP functions as a positive regulator of Wnt/beta-catenin/T-cell factor signaling in neoplastic transformation. Cancer Res 67:482–491PubMedGoogle Scholar
  40. Ferkey DM, Kimelman D (2002) Glycogen synthase kinase-3 beta mutagenesis identifies a common binding domain for GBP and Axin. J Biol Chem 277:16147–16152PubMedGoogle Scholar
  41. 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 USA 94:6770–6775PubMedGoogle Scholar
  42. Galceran J, Farinas I, Depew MJ, Clevers H, Grosschedl R (1999) Wnt3a-/-like phenotype and limb deficiency in Lef1(−/−)Tcf1(−/−) mice. Genes Dev 13:709–717PubMedGoogle Scholar
  43. Galceran J, Miyashita-Lin EM, Devaney E, Rubenstein JL, Grosschedl R (2000) Hippocampus development and generation of dentate gyrus granule cells is regulated by LEF1. Development 127:469–482PubMedGoogle Scholar
  44. Gay F, Calvo D, Lo MC, Ceron J, Maduro M, Lin R, Shi Y (2003) Acetylation regulates subcellular localization of the Wnt signaling nuclear effector POP-1. Genes Dev 17:717–722PubMedGoogle Scholar
  45. Ge S, Goh EL, Sailor KA, Kitabatake Y, Ming GL, Song H (2006) GABA regulates synaptic integration of newly generated neurons in the adult brain. Nature 439:589–593PubMedGoogle Scholar
  46. Ghogomu SM, van Venrooy S, Ritthaler M, Wedlich D, Gradl D (2006) HIC-5 is a novel repressor of lymphoid enhancer factor/T-cell factor-driven transcription. J Biol Chem 281:1755–1764PubMedGoogle Scholar
  47. 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 391:357–362PubMedGoogle Scholar
  48. Gould E, Cameron HA, McEwen BS (1994) Blockade of NMDA receptors increases cell death and birth in the developing rat dentate gyrus. J Comp Neurol 340:551–565PubMedGoogle Scholar
  49. Gradl D, Konig A, Wedlich D (2002) Functional diversity of Xenopus lymphoid enhancer factor/T-cell factor transcription factors relies on combinations of activating and repressing elements. J Biol Chem 277:14159–14171PubMedGoogle Scholar
  50. Graham V, Khudyakov J, Ellis P, Pevny L (2003) SOX2 functions to maintain neural progenitor identity. Neuron 39:749–765PubMedGoogle Scholar
  51. Gunhaga L, Marklund M, Sjodal M, Hsieh JC, Jessell TM, Edlund T (2003) Specification of dorsal telencephalic character by sequential Wnt and FGF signaling. Nat Neurosci 6:701–707PubMedGoogle Scholar
  52. Habas R, Dawid IB (2005) Dishevelled and Wnt signaling: is the nucleus the final frontier? J Biol 4:2PubMedGoogle Scholar
  53. Habas R, Dawid IB, He X (2003) Coactivation of Rac and Rho by Wnt/Frizzled signaling is required for vertebrate gastrulation. Genes Dev 17:295–309PubMedGoogle Scholar
  54. Hall AC, Lucas FR, Salinas PC (2000) Axonal remodeling and synaptic differentiation in the cerebellum is regulated by WNT-7a signaling. Cell 100:525–535PubMedGoogle Scholar
  55. Hamada F, Bienz M (2004) The APC tumor suppressor binds to C-terminal binding protein to divert nuclear beta-catenin from TCF. Dev Cell 7:677–685PubMedGoogle Scholar
  56. Hammerlein A, Weiske J, Huber O (2005) A second protein kinase CK1-mediated step negatively regulates Wnt signalling by disrupting the lymphocyte enhancer factor-1/beta-catenin complex. Cell Mol Life Sci 62:606–618PubMedGoogle Scholar
  57. Hay E, Faucheu C, Suc-Royer I, Touitou R, Stiot V, Vayssiere B, Baron R, Roman-Roman S, Rawadi G (2005) Interaction between LRP5 and Frat1 mediates the activation of the Wnt canonical pathway. J Biol Chem 280:13616–13623PubMedGoogle Scholar
  58. Hayden MA, Akong K, Peifer M (2007) Novel roles for APC family members and Wingless/Wnt signaling during Drosophila brain development. Dev Biol 305:358–376PubMedGoogle Scholar
  59. He F, Ge W, Martinowich K, Becker-Catania S, Coskun V, Zhu W, Wu H, Castro D, Guillemot F, Fan G, de Vellis J, Sun YE (2005) A positive autoregulatory loop of Jak-STAT signaling controls the onset of astrogliogenesis. Nat Neurosci 8:616–625PubMedGoogle Scholar
  60. He X, Axelrod JD (2006) A WNTer wonderland in Snowbird. Development 133:2597–2603PubMedGoogle Scholar
  61. He XC, Zhang J, Tong WG, Tawfik O, Ross J, Scoville DH, Tian Q, Zeng X, He X, Wiedemann LM, Mishina Y, Li L (2004) BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-beta-catenin signaling. Nat Genet 36:1117–1121PubMedGoogle Scholar
  62. Hecht A, Stemmler MP (2003) Identification of a promoter-specific transcriptional activation domain at the C terminus of the Wnt effector protein T-cell factor 4. J Biol Chem 278:3776–3785PubMedGoogle Scholar
  63. Hikasa H, Sokol SY (2004) The involvement of Frodo in TCF-dependent signaling and neural tissue development. Development 131:4725–4734PubMedGoogle Scholar
  64. Hildebrand JD, Soriano P (2002) Overlapping and unique roles for C-terminal binding protein 1 (CtBP1) and CtBP2 during mouse development. Mol Cell Biol 22:5296–5307PubMedGoogle Scholar
  65. Hirabayashi Y, Gotoh Y (2005) Stage-dependent fate determination of neural precursor cells in mouse forebrain. Neurosci Res 51:331–336PubMedGoogle Scholar
  66. Hirabayashi Y, Itoh Y, Tabata H, Nakajima K, Akiyama T, Masuyama N, Gotoh Y (2004) The Wnt/beta-catenin pathway directs neuronal differentiation of cortical neural precursor cells. Development 131:2791–2801PubMedGoogle Scholar
  67. Hiriart E, Gruffat H, Buisson M, Mikaelian I, Keppler S, Meresse P, Mercher T, Bernard OA, Sergeant A, Manet E (2005) Interaction of the Epstein-Barr virus mRNA export factor EB2 with human Spen proteins SHARP, OTT1, and a novel member of the family, OTT3, links Spen proteins with splicing regulation and mRNA export. J Biol Chem 280:36935–36945PubMedGoogle Scholar
  68. Hirsch C, Campano LM, Wohrle S, Hecht A (2007) Canonical Wnt signaling transiently stimulates proliferation and enhances neurogenesis in neonatal neural progenitor cultures. Exp Cell Res 313:572–587PubMedGoogle Scholar
  69. 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 271:26131–26137PubMedGoogle Scholar
  70. Hoffmans R, Basler K (2007) BCL9-2 binds Arm/beta-catenin in a Tyr142-independent manner and requires Pygopus for its function in Wg/Wnt signaling. Mech Dev 124:59–67PubMedGoogle Scholar
  71. Hofmann K (2000) A superfamily of membrane-bound O-acyltransferases with implications for wnt signaling. Trends Biochem Sci 25:111–112PubMedGoogle Scholar
  72. Hollyday M, McMahon JA, McMahon AP (1995) Wnt expression patterns in chick embryo nervous system. Mech Dev 52:9–25PubMedGoogle Scholar
  73. Houston DW, Kofron M, Resnik E, Langland R, Destree O, Wylie C, Heasman J (2002) Repression of organizer genes in dorsal and ventral Xenopus cells mediated by maternal XTcf3. Development 129:4015–4025PubMedGoogle Scholar
  74. Hovanes K, Li TW, Munguia JE, Truong T, Milovanovic T, Lawrence Marsh J, Holcombe RF, Waterman ML (2001) Beta-catenin-sensitive isoforms of lymphoid enhancer factor-1 are selectively expressed in colon cancer. Nat Genet 28:53–57PubMedGoogle Scholar
  75. Hsieh JC (2004) Specificity of WNT-receptor interactions. Front Biosci 9:1333–1338PubMedGoogle Scholar
  76. 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 398:431–436PubMedGoogle Scholar
  77. Hsieh JC, Lee L, Zhang L, Wefer S, Brown K, DeRossi C, Wines ME, Rosenquist T, Holdener BC (2003) Mesd encodes an LRP5/6 chaperone essential for specification of mouse embryonic polarity. Cell 112:355–367PubMedGoogle Scholar
  78. Hu MC, Rosenblum ND (2005) Smad1, beta-catenin and Tcf4 associate in a molecular complex with the Myc promoter in dysplastic renal tissue and cooperate to control Myc transcription. Development 132:215–225PubMedGoogle Scholar
  79. Hurlstone A, Clevers H (2002) T-cell factors: turn-ons and turn-offs. EMBO J 21:2303–2311PubMedGoogle Scholar
  80. Hussein SM, Duff EK, Sirard C (2003) Smad4 and beta-catenin co-activators functionally interact with lymphoid-enhancing factor to regulate graded expression of Msx2. J Biol Chem 278:48805–48814PubMedGoogle Scholar
  81. Ille F, Atanasoski S, Falk S, Ittner LM, Marki D, Buchmann-Moller S, Wurdak H, Suter U, Taketo MM, Sommer L (2007) Wnt/BMP signal integration regulates the balance between proliferation and differentiation of neuroepithelial cells in the dorsal spinal cord. Dev Biol 304:394–408PubMedGoogle Scholar
  82. Ilyas M (2005) Wnt signalling and the mechanistic basis of tumour development. J Pathol 205:130–144PubMedGoogle Scholar
  83. Ishitani T, Ninomiya-Tsuji J, Matsumoto K (2003) Regulation of lymphoid enhancer factor 1/T-cell factor by mitogen-activated protein kinase-related Nemo-like kinase-dependent phosphorylation in Wnt/beta-catenin signaling. Mol Cell Biol 23:1379–1389PubMedGoogle Scholar
  84. Israsena N, Hu M, Fu W, Kan L, Kessler JA (2004) The presence of FGF2 signaling determines whether beta-catenin exerts effects on proliferation or neuronal differentiation of neural stem cells. Dev Biol 268:220–231PubMedGoogle Scholar
  85. Itoh K, Brott BK, Bae GU, Ratcliffe MJ, Sokol SY (2005) Nuclear localization is required for Dishevelled function in Wnt/beta-catenin signaling. J Biol 4:3PubMedGoogle Scholar
  86. Jagasia R, Song H, Gage FH, Lie DC (2006) New regulators in adult neurogenesis and their potential role for repair. Trends Mol Med 12:400–405PubMedGoogle Scholar
  87. Kaphingst K, Kunes S (1994) Pattern formation in the visual centers of the Drosophila brain: wingless acts via decapentaplegic to specify the dorsoventral axis. Cell 78:437–448PubMedGoogle Scholar
  88. Kawano Y, Kypta R (2003) Secreted antagonists of the Wnt signalling pathway. J Cell Sci 116:2627–2634PubMedGoogle Scholar
  89. Kazanskaya O, Glinka A, del Barco Barrantes I, Stannek P, Niehrs C, Wu W (2004) R-Spondin2 is a secreted activator of Wnt/beta-catenin signaling and is required for Xenopus myogenesis. Dev Cell 7:525–534PubMedGoogle Scholar
  90. Kiecker C, Niehrs C (2001) A morphogen gradient of Wnt/beta-catenin signalling regulates anteroposterior neural patterning in Xenopus. Development 128:4189–4201PubMedGoogle Scholar
  91. Kikuchi A, Yamamoto H, Kishida S (2007) Multiplicity of the interactions of Wnt proteins and their receptors. Cell Signal 19:659–671PubMedGoogle Scholar
  92. Kim KA, Kakitani M, Zhao J, Oshima T, Tang T, Binnerts M, Liu Y, Boyle B, Park E, Emtage P, Funk WD, Tomizuka K (2005) Mitogenic influence of human R-spondin1 on the intestinal epithelium. Science 309:1256–1259PubMedGoogle Scholar
  93. Kioussi C, Briata P, Baek SH, Rose DW, Hamblet NS, Herman T, Ohgi KA, Lin C, Gleiberman A, Wang J, Brault V, Ruiz-Lozano P, Nguyen HD, Kemler R, Glass CK, Wynshaw-Boris A, Rosenfeld MG (2002) Identification of a Wnt/Dvl/beta-Catenin −> Pitx2 pathway mediating cell-type-specific proliferation during development. Cell 111:673–685PubMedGoogle Scholar
  94. Kishida M, Hino S, Michiue T, Yamamoto H, Kishida S, Fukui A, Asashima M, Kikuchi A (2001) Synergistic activation of the Wnt signaling pathway by Dvl and casein kinase Iepsilon. J Biol Chem 276:33147–33155PubMedGoogle Scholar
  95. Kleber M, Lee HY, Wurdak H, Buchstaller J, Riccomagno MM, Ittner LM, Suter U, Epstein DJ, Sommer L (2005) Neural crest stem cell maintenance by combinatorial Wnt and BMP signaling. J Cell BiolGoogle Scholar
  96. Klein TJ, Mlodzik M (2005) Planar cell polarization: an emerging model points in the right direction. Annu Rev Cell Dev Biol 21:155–176PubMedGoogle Scholar
  97. Kohn AD, Moon RT (2005) Wnt and calcium signaling: beta-catenin-independent pathways. Cell Calcium 38:439–446PubMedGoogle Scholar
  98. Korinek V, Barker N, Moerer P, van Donselaar E, Huls G, Peters PJ, Clevers H (1998) Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4. Nat Genet 19:379–383PubMedGoogle Scholar
  99. Krupnik VE, Sharp JD, Jiang C, Robison K, Chickering TW, Amaravadi L, Brown DE, Guyot D, Mays G, Leiby K, Chang B, Duong T, Goodearl AD, Gearing DP, Sokol SY, McCarthy SA (1999) Functional and structural diversity of the human Dickkopf gene family. Gene 238:301–313PubMedGoogle Scholar
  100. Krylova O, Herreros J, Cleverley KE, Ehler E, Henriquez JP, Hughes SM, Salinas PC (2002) WNT-3, expressed by motoneurons, regulates terminal arborization of neurotrophin-3-responsive spinal sensory neurons. Neuron 35:1043–1056PubMedGoogle Scholar
  101. Kuang B, Wu SC, Shin Y, Luo L, Kolodziej P (2000) split ends encodes large nuclear proteins that regulate neuronal cell fate and axon extension in the Drosophila embryo. Development 127:1517–1529PubMedGoogle Scholar
  102. Kuhl M (2004) The WNT/calcium pathway: biochemical mediators, tools and future requirements. Front Biosci 9:967–974PubMedGoogle Scholar
  103. Kuwabara T, Hsieh J, Nakashima K, Taira K, Gage FH (2004) A small modulatory dsRNA specifies the fate of adult neural stem cells. Cell 116:779–793PubMedGoogle Scholar
  104. Labbe E, Letamendia A, Attisano L (2000) Association of Smads with lymphoid enhancer binding factor 1/T cell-specific factor mediates cooperative signaling by the transforming growth factor-beta and wnt pathways. Proc Natl Acad Sci USA 97:8358–8363PubMedGoogle Scholar
  105. Lane ME, Elend M, Heidmann D, Herr A, Marzodko S, Herzig A, Lehner CF (2000) A screen for modifiers of cyclin E function in Drosophila melanogaster identifies Cdk2 mutations, revealing the insignificance of putative phosphorylation sites in Cdk2. Genetics 155:233–244Google Scholar
  106. Lee E, Salic A, Kirschner MW (2001) Physiological regulation of [beta]-catenin stability by Tcf3 and CK1epsilon. J Cell Biol 154:983–993PubMedGoogle Scholar
  107. Lee HY, Kleber M, Hari L, Brault V, Suter U, Taketo MM, Kemler R, Sommer L (2004) Instructive role of Wnt/beta-catenin in sensory fate specification in neural crest stem cells. Science 303:1020–1023PubMedGoogle Scholar
  108. Lee SM, Tole S, Grove E, McMahon AP (2000) A local Wnt-3a signal is required for development of the mammalian hippocampus. Development 127:457–467PubMedGoogle Scholar
  109. 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 88:747–756PubMedGoogle Scholar
  110. 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 277:5977–5981PubMedGoogle Scholar
  111. Li L, Yuan H, Weaver CD, Mao J, Farr GH 3rd, Sussman DJ, Jonkers J, Kimelman D, Wu D (1999) Axin and Frat1 interact with dvl and GSK, bridging Dvl to GSK in Wnt-mediated regulation of LEF-1. EMBO J 18:4233–4240PubMedGoogle Scholar
  112. Lie DC, Dziewczapolski G, Willhoite AR, Kaspar BK, Shults CW, Gage FH (2002) The adult substantia nigra contains progenitor cells with neurogenic potential. J Neurosci 22:6639–6649PubMedGoogle Scholar
  113. Lie DC, Colamarino SA, Song HJ, Desire L, Mira H, Consiglio A, Lein ES, Jessberger S, Lansford H, Dearie AR, Gage FH (2005) Wnt signalling regulates adult hippocampal neurogenesis. Nature 437:1370–1375PubMedGoogle Scholar
  114. Lim DA, Alvarez-Buylla A (1999) Interaction between astrocytes and adult subventricular zone precursors stimulates neurogenesis. Proc Natl Acad Sci USA 96:7526–7531PubMedGoogle Scholar
  115. Lin X, Liang YY, Sun B, Liang M, Shi Y, Brunicardi FC, Shi Y, Feng XH (2003) Smad6 recruits transcription corepressor CtBP to repress bone morphogenetic protein-induced transcription. Mol Cell Biol 23:9081–9093PubMedGoogle Scholar
  116. Liu Y, Shi J, Lu CC, Wang ZB, Lyuksyutova AI, Song XJ, Zou Y (2005) Ryk-mediated Wnt repulsion regulates posterior-directed growth of corticospinal tract. Nat Neurosci 8:1151–1159PubMedGoogle Scholar
  117. Lo MC, Gay F, Odom R, Shi Y, Lin R (2004) Phosphorylation by the beta-catenin/MAPK complex promotes 14-3-3-mediated nuclear export of TCF/POP-1 in signal-responsive cells in C. elegans. Cell 117:95–106PubMedGoogle Scholar
  118. Logan CY, Nusse R (2004) The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 20:781–810PubMedGoogle Scholar
  119. Lowry WE, Blanpain C, Nowak JA, Guasch G, Lewis L, Fuchs E (2005) Defining the impact of beta-catenin/Tcf transactivation on epithelial stem cells. Genes Dev 19:1596–1611PubMedGoogle Scholar
  120. Lu W, Yamamoto V, Ortega B, Baltimore D (2004) Mammalian Ryk is a Wnt coreceptor required for stimulation of neurite outgrowth. Cell 119:97–108PubMedGoogle Scholar
  121. Lyuksyutova AI, Lu CC, Milanesio N, King LA, Guo N, Wang Y, Nathans J, Tessier-Lavigne M, Zou Y (2003) Anterior-posterior guidance of commissural axons by Wnt-frizzled signaling. Science 302:1984–1988PubMedGoogle Scholar
  122. Machon O, van den Bout CJ, Backman M, Kemler R, Krauss S (2003) Role of beta-catenin in the developing cortical and hippocampal neuroepithelium. Neuroscience 122:129–143PubMedGoogle Scholar
  123. Malbon CC, Wang HY (2006) Dishevelled: a mobile scaffold catalyzing development. Curr Top Dev Biol 72:153–166PubMedGoogle Scholar
  124. Mansukhani A, Ambrosetti D, Holmes G, Cornivelli L, Basilico C (2005) Sox2 induction by FGF and FGFR2 activating mutations inhibits Wnt signaling and osteoblast differentiation. J Cell Biol 168:1065–1076PubMedGoogle Scholar
  125. Mao J, Wang J, Liu B, Pan W, Farr GH 3rd, Flynn C, Yuan H, Takada S, Kimelman D, Li L, Wu D (2001) Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway. Mol Cell 7:801–809PubMedGoogle Scholar
  126. Mao B, Wu W, Davidson G, Marhold J, Li M, Mechler BM, Delius H, Hoppe D, Stannek P, Walter C, Glinka A, Niehrs C (2002) Kremen proteins are Dickkopf receptors that regulate Wnt/beta-catenin signalling. Nature 417:664–667PubMedGoogle Scholar
  127. Maretto S, Cordenonsi M, Dupont S, Braghetta P, Broccoli V, Hassan AB, Volpin D, Bressan GM, Piccolo S (2003) Mapping Wnt/beta-catenin signaling during mouse development and in colorectal tumors. Proc Natl Acad Sci USA 100:3299–3304PubMedGoogle Scholar
  128. McGrew LL, Lai CJ, Moon RT (1995) Specification of the anteroposterior neural axis through synergistic interaction of the Wnt signaling cascade with noggin and follistatin. Dev Biol 172:337–342PubMedGoogle Scholar
  129. McMahon AP, Bradley A (1990) The Wnt-1 (int-1) proto-oncogene is required for development of a large region of the mouse brain. Cell 62:1073–1085PubMedGoogle Scholar
  130. Megason SG, McMahon AP (2002) A mitogen gradient of dorsal midline Wnts organizes growth in the CNS. Development 129:2087–2098PubMedGoogle Scholar
  131. Merrill BJ, Gat U, DasGupta R, Fuchs E (2001) Tcf3 and Lef1 regulate lineage differentiation of multipotent stem cells in skin. Genes Dev 15:1688–1705PubMedGoogle Scholar
  132. Merrill BJ, Pasolli HA, Polak L, Rendl M, Garcia-Garcia MJ, Anderson KV, Fuchs E (2004) Tcf3: a transcriptional regulator of axis induction in the early embryo. Development 131:263–274PubMedGoogle Scholar
  133. Mikels AJ, Nusse R (2006) Purified Wnt5a protein activates or inhibits beta-catenin-TCF signaling depending on receptor context. PLoS Biol 4:e115PubMedGoogle Scholar
  134. Ming GL, Song H (2005) Adult neurogenesis in the mammalian central nervous system. Annu Rev Neurosci 28:223–250PubMedGoogle Scholar
  135. Miravet S, Piedra J, Miro F, Itarte E, Garcia de Herreros A, Dunach M (2002) The transcriptional factor Tcf-4 contains different binding sites for beta-catenin and plakoglobin. J Biol Chem 277:1884–1891PubMedGoogle Scholar
  136. Miyabayashi T, Teo JL, Yamamoto M, McMillan M, Nguyen C, Kahn M (2007) Wnt/beta-catenin/CBP signaling maintains long-term murine embryonic stem cell pluripotency. Proc Natl Acad Sci USA 104:5668–5673PubMedGoogle Scholar
  137. Moriguchi T, Kawachi K, Kamakura S, Masuyama N, Yamanaka H, Matsumoto K, Kikuchi A, Nishida E (1999) Distinct domains of mouse dishevelled are responsible for the c-Jun N-terminal kinase/stress-activated protein kinase activation and the axis formation in vertebrates. J Biol Chem 274:30957–30962PubMedGoogle Scholar
  138. Muroyama Y, Fujihara M, Ikeya M, Kondoh H, Takada S (2002) Wnt signaling plays an essential role in neuronal specification of the dorsal spinal cord. Genes Dev 16:548–553PubMedGoogle Scholar
  139. Muzio L, Soria JM, Pannese M, Piccolo S, Mallamaci A (2005) A mutually stimulating loop involving emx2 and canonical wnt signalling specifically promotes expansion of occipital cortex and hippocampus. Cereb Cortex 15:2021–2028PubMedGoogle Scholar
  140. Nagel AC, Krejci A, Tenin G, Bravo-Patino A, Bray S, Maier D, Preiss A (2005) Hairless-mediated repression of notch target genes requires the combined activity of Groucho and CtBP corepressors. Mol Cell Biol 25:10433–10441PubMedGoogle Scholar
  141. 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 beta-catenin-dependent gene expression. J Biol Chem 281:13247–13257PubMedGoogle Scholar
  142. Nishihara S, Tsuda L, Ogura T (2003) The canonical Wnt pathway directly regulates NRSF/REST expression in chick spinal cord. Biochem Biophys Res Commun 311:55–63PubMedGoogle Scholar
  143. Nishita M, Hashimoto MK, Ogata S, Laurent MN, Ueno N, Shibuya H, Cho KW (2000) Interaction between Wnt and TGF-beta signalling pathways during formation of Spemann’s organizer. Nature 403:781–785PubMedGoogle Scholar
  144. Nusse R, Varmus HE (1982) Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell 31:99–109PubMedGoogle Scholar
  145. Olson LE, Tollkuhn J, Scafoglio C, Krones A, Zhang J, Ohgi KA, Wu W, Taketo MM, Kemler R, Grosschedl R, Rose D, Li X, Rosenfeld MG (2006) Homeodomain-mediated beta-catenin-dependent switching events dictate cell-lineage determination. Cell 125:593–605PubMedGoogle Scholar
  146. Oswald F, Kostezka U, Astrahantseff K, Bourteele S, Dillinger K, Zechner U, Ludwig L, Wilda M, Hameister H, Knochel W, Liptay S, Schmid RM (2002) SHARP is a novel component of the Notch/RBP-Jkappa signalling pathway. EMBO J 21:5417–5426PubMedGoogle Scholar
  147. Oswald F, Winkler M, Cao Y, Astrahantseff K, Bourteele S, Knochel W, Borggrefe T (2005) RBP-Jkappa/SHARP recruits CtIP/CtBP corepressors to silence Notch target genes. Mol Cell Biol 25:10379–10390PubMedGoogle Scholar
  148. Overstreet-Wadiche LS, Bensen AL, Westbrook GL (2006) Delayed development of adult-generated granule cells in dentate gyrus. J Neurosci 26:2326–2334PubMedGoogle Scholar
  149. Panakova D, Sprong H, Marois E, Thiele C, Eaton S (2005) Lipoprotein particles are required for Hedgehog and Wingless signalling. Nature 435:58–65PubMedGoogle Scholar
  150. Panhuysen M, Vogt Weisenhorn DM, Blanquet V, Brodski C, Heinzmann U, Beisker W, Wurst W (2004) Effects of Wnt1 signaling on proliferation in the developing mid-/hindbrain region. Mol Cell Neurosci 26:101–111PubMedGoogle Scholar
  151. Pereira L, Yi F, Merrill BJ (2006) Repression of Nanog gene transcription by Tcf3 limits embryonic stem cell self-renewal. Mol Cell Biol 26:7479–7491PubMedGoogle Scholar
  152. 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 397:707–710PubMedGoogle Scholar
  153. Pinson KI, Brennan J, Monkley S, Avery BJ, Skarnes WC (2000) An LDL-receptor-related protein mediates Wnt signalling in mice. Nature 407:535–538PubMedGoogle Scholar
  154. Prakash N, Brodski C, Naserke T, Puelles E, Gogoi R, Hall A, Panhuysen M, Echevarria D, Sussel L, Weisenhorn DM, Martinez S, Arenas E, Simeone A, Wurst W (2006) A Wnt1-regulated genetic network controls the identity and fate of midbrain-dopaminergic progenitors in vivo. Development 133:89–98PubMedGoogle Scholar
  155. Prasad BC, Clark SG (2006) Wnt signaling establishes anteroposterior neuronal polarity and requires retromer in C. elegans. Development 133:1757–1766PubMedGoogle Scholar
  156. Riese J, Yu X, Munnerlyn A, Eresh S, Hsu SC, Grosschedl R, Bienz M (1997) LEF-1, a nuclear factor coordinating signaling inputs from wingless and decapentaplegic. Cell 88:777–787PubMedGoogle Scholar
  157. Roose J, Huls G, van Beest M, Moerer P, van der Horn K, Goldschmeding R, Logtenberg T, Clevers H (1999) Synergy between tumor suppressor APC and the beta-catenin-Tcf4 target Tcf1. Science 285:1923–1926PubMedGoogle Scholar
  158. Rosso SB, Sussman D, Wynshaw-Boris A, Salinas PC (2005) Wnt signaling through Dishevelled, Rac and JNK regulates dendritic development. Nat Neurosci 8:34–42PubMedGoogle Scholar
  159. Sachdev S, Bruhn L, Sieber H, Pichler A, Melchior F, Grosschedl R (2001) PIASy, a nuclear matrix-associated SUMO E3 ligase, represses LEF1 activity by sequestration into nuclear bodies. Genes Dev 15:3088–3103PubMedGoogle Scholar
  160. Sato N, Meijer L, Skaltsounis L, Greengard P, Brivanlou AH (2004) Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor. Nat Med 10:55–63PubMedGoogle Scholar
  161. Satoh K, Kasai M, Ishidao T, Tago K, Ohwada S, Hasegawa Y, Senda T, Takada S, Nada S, Nakamura T, Akiyama T (2004) Anteriorization of neural fate by inhibitor of beta-catenin and T cell factor (ICAT), a negative regulator of Wnt signaling. Proc Natl Acad Sci USA 101:8017–8021PubMedGoogle Scholar
  162. Schwarz-Romond T, Merrifield C, Nichols BJ, Bienz M (2005) The Wnt signalling effector Dishevelled forms dynamic protein assemblies rather than stable associations with cytoplasmic vesicles. J Cell Sci 118:5269–5277PubMedGoogle Scholar
  163. Shi Y, Downes M, Xie W, Kao HY, Ordentlich P, Tsai CC, Hon M, Evans RM (2001) Sharp, an inducible cofactor that integrates nuclear receptor repression and activation. Genes Dev 15:1140–1151PubMedGoogle Scholar
  164. Shihabuddin LS, Horner PJ, Ray J, Gage FH (2000) Adult spinal cord stem cells generate neurons after transplantation in the adult dentate gyrus. J Neurosci 20:8727–8735PubMedGoogle Scholar
  165. Shimogori T, VanSant J, Paik E, Grove EA (2004) Members of the Wnt, Fz, and Frp gene families expressed in postnatal mouse cerebral cortex. J Comp Neurol 473:496–510PubMedGoogle Scholar
  166. Sierra OL, Cheng SL, Loewy AP, Charlton-Kachigian N, Towler DA (2004) MINT, the Msx2 interacting nuclear matrix target, enhances Runx2-dependent activation of the osteocalcin fibroblast growth factor response element. J Biol Chem 279:32913–32923Google Scholar
  167. Sierra J, Yoshida T, Joazeiro CA, Jones KA (2006) The APC tumor suppressor counteracts beta-catenin activation and H3K4 methylation at Wnt target genes. Genes Dev 20:586–600PubMedGoogle Scholar
  168. Sinner D, Rankin S, Lee M, Zorn AM (2004) Sox17 and beta-catenin cooperate to regulate the transcription of endodermal genes. Development 131:3069–3080PubMedGoogle Scholar
  169. Snider L, Thirlwell H, Miller JR, Moon RT, Groudine M, Tapscott SJ (2001) Inhibition of Tcf3 binding by I-mfa domain proteins. Mol Cell Biol 21:1866–1873PubMedGoogle Scholar
  170. Song Y, Chung S, Kunes S (2000) Combgap relays wingless signal reception to the determination of cortical cell fate in the Drosophila visual system. Mol Cell 6:1143–1154PubMedGoogle Scholar
  171. Song H, Stevens CF, Gage FH (2002) Astroglia induce neurogenesis from adult neural stem cells. Nature 417:39–44PubMedGoogle Scholar
  172. Stadeli R, Basler K (2005) Dissecting nuclear Wingless signalling: recruitment of the transcriptional co-activator Pygopus by a chain of adaptor proteins. Mech Dev 122:1171–1182PubMedGoogle Scholar
  173. Stadeli R, Hoffmans R, Basler K (2006) Transcription under the control of nuclear Arm/beta-catenin. Curr Biol 16:R378–R385PubMedGoogle Scholar
  174. Standley HJ, Destree O, Kofron M, Wylie C, Heasman J (2006) Maternal XTcf1 and XTcf4 have distinct roles in regulating Wnt target genes. Dev Biol 289:318–328PubMedGoogle Scholar
  175. Suhonen JO, Peterson DA, Ray J, Gage FH (1996) Differentiation of adult hippocampus-derived progenitors into olfactory neurons in vivo. Nature 383:624–627PubMedGoogle Scholar
  176. Tago K, Nakamura T, Nishita M, Hyodo J, Nagai S, Murata Y, Adachi S, Ohwada S, Morishita Y, Shibuya H, Akiyama T (2000) Inhibition of Wnt signaling by ICAT, a novel beta-catenin-interacting protein. Genes Dev 14:1741–1749PubMedGoogle Scholar
  177. Takemaru K, Yamaguchi S, Lee YS, Zhang Y, Carthew RW, Moon RT (2003) Chibby, a nuclear beta-catenin-associated antagonist of the Wnt/Wingless pathway. Nature 422:905–909PubMedGoogle Scholar
  178. Takemoto T, Uchikawa M, Kamachi Y, Kondoh H (2006) Convergence of Wnt and FGF signals in the genesis of posterior neural plate through activation of the Sox2 enhancer N-1. Development 133:297–306PubMedGoogle Scholar
  179. Takizawa T, Nakashima K, Namihira M, Ochiai W, Uemura A, Yanagisawa M, Fujita N, Nakao M, Taga T (2001) DNA methylation is a critical cell-intrinsic determinant of astrocyte differentiation in the fetal brain. Dev Cell 1:749–758PubMedGoogle Scholar
  180. Tamai K, Semenov M, Kato Y, Spokony R, Liu C, Katsuyama Y, Hess F, Saint-Jeannet JP, He X (2000) LDL-receptor-related proteins in Wnt signal transduction. Nature 407:530–535PubMedGoogle Scholar
  181. Tarui T, Takahashi T, Nowakowski RS, Hayes NL, Bhide PG, Caviness VS (2005) Overexpression of p27 Kip 1, probability of cell cycle exit, and laminar destination of neocortical neurons. Cereb Cortex 15:1343–1355PubMedGoogle Scholar
  182. Tashiro A, Sandler VM, Toni N, Zhao C, Gage FH (2006) NMDA-receptor-mediated, cell-specific integration of new neurons in adult dentate gyrus. Nature 442:929–933PubMedGoogle Scholar
  183. Teo JL, Ma H, Nguyen C, Lam C, Kahn M (2005) Specific inhibition of CBP/beta-catenin interaction rescues defects in neuronal differentiation caused by a presenilin-1 mutation. Proc Natl Acad Sci USA 102:12171–12176PubMedGoogle Scholar
  184. Theil T, Aydin S, Koch S, Grotewold L, Ruther U (2002) Wnt and Bmp signalling cooperatively regulate graded Emx2 expression in the dorsal telencephalon. Development 129:3045–3054PubMedGoogle Scholar
  185. Thomas KR, Capecchi MR (1990) Targeted disruption of the murine int-1 proto-oncogene resulting in severe abnormalities in midbrain and cerebellar development. Nature 346:847–850PubMedGoogle Scholar
  186. Tole S, Goudreau G, Assimacopoulos S, Grove EA (2000) Emx2 is required for growth of the hippocampus but not for hippocampal field specification. J Neurosci 20:2618–2625PubMedGoogle Scholar
  187. Topol L, Jiang X, Choi H, Garrett-Beal L, Carolan PJ, Yang Y (2003) Wnt-5a inhibits the canonical Wnt pathway by promoting GSK-3-independent beta-catenin degradation. J Cell Biol 162:899–908PubMedGoogle Scholar
  188. Townsley FM, Cliffe A, Bienz M (2004) Pygopus and Legless target Armadillo/beta-catenin to the nucleus to enable its transcriptional co-activator function. Nat Cell Biol 6:626–633PubMedGoogle Scholar
  189. Tozuka Y, Fukuda S, Namba T, Seki T, Hisatsune T (2005) GABAergic excitation promotes neuronal differentiation in adult hippocampal progenitor cells. Neuron 47:803–815PubMedGoogle Scholar
  190. Vadlamudi U, Espinoza HM, Ganga M, Martin DM, Liu X, Engelhardt JF, Amendt BA (2005) PITX2, beta-catenin and LEF-1 interact to synergistically regulate the LEF-1 promoter. J Cell Sci 118:1129–1137PubMedGoogle Scholar
  191. Valenta T, Lukas J, Korinek V (2003) HMG box transcription factor TCF-4’s interaction with CtBP1 controls the expression of the Wnt target Axin2/Conductin in human embryonic kidney cells. Nucleic Acids Res 31:2369–2380PubMedGoogle Scholar
  192. Valenta T, Lukas J, Doubravska L, Fafilek B, Korinek V (2006) HIC1 attenuates Wnt signaling by recruitment of TCF-4 and beta-catenin to the nuclear bodies. EMBO J 25:2326–2337PubMedGoogle Scholar
  193. Van de Wetering M, Castrop J, Korinek V, Clevers H (1996) Extensive alternative splicing and dual promoter usage generate Tcf-1 protein isoforms with differential transcription control properties. Mol Cell Biol 16:745–752PubMedGoogle Scholar
  194. van Es JH, Barker N, Clevers H (2003) You Wnt some, you lose some: oncogenes in the Wnt signaling pathway. Curr Opin Genet Dev 13:28–33PubMedGoogle Scholar
  195. Van Raay TJ, Moore KB, Iordanova I, Steele M, Jamrich M, Harris WA, Vetter ML (2005) Frizzled 5 signaling governs the neural potential of progenitors in the developing Xenopus retina. Neuron 46:23–36PubMedGoogle Scholar
  196. van Roy FM, McCrea PD (2005) A role for Kaiso-p120ctn complexes in cancer? Nat Rev Cancer 5:956–964PubMedGoogle Scholar
  197. Veeman MT, Axelrod JD, Moon RT (2003) A second canon. Functions and mechanisms of beta-catenin-independent Wnt signaling. Dev Cell 5:367–377PubMedGoogle Scholar
  198. Viti J, Gulacsi A, Lillien L (2003) Wnt regulation of progenitor maturation in the cortex depends on Shh or fibroblast growth factor 2. J Neurosci 23:5919–5927PubMedGoogle Scholar
  199. Wallingford JB, Habas R (2005) The developmental biology of Dishevelled: an enigmatic protein governing cell fate and cell polarity. Development 132:4421–4436PubMedGoogle Scholar
  200. Wang HY, Malbon CC (2003) Wnt signaling, Ca2+, and cyclic GMP: visualizing Frizzled functions. Science 300:1529–1530PubMedGoogle Scholar
  201. Wang LP, Kempermann G, Kettenmann H (2005) A subpopulation of precursor cells in the mouse dentate gyrus receives synaptic GABAergic input. Mol Cell Neurosci 29:181–189PubMedGoogle Scholar
  202. Wayman GA, Impey S, Marks D, Saneyoshi T, Grant WF, Derkach V, Soderling TR (2006) Activity-dependent dendritic arborization mediated by CaM-kinase I activation and enhanced CREB-dependent transcription of Wnt-2. Neuron 50:897–909PubMedGoogle Scholar
  203. Weerkamp F, Baert MR, Naber BA, Koster EE, de Haas EF, Atkuri KR, van Dongen JJ, Herzenberg LA, Staal FJ (2006) Wnt signaling in the thymus is regulated by differential expression of intracellular signaling molecules. Proc Natl Acad Sci USA 103:3322–3326PubMedGoogle Scholar
  204. Wehrli M, Dougan ST, Caldwell K, O’Keefe L, Schwartz S, Vaizel-Ohayon D, Schejter E, Tomlinson A, DiNardo S (2000) arrow encodes an LDL-receptor-related protein essential for Wingless signalling. Nature 407:527–530PubMedGoogle Scholar
  205. Weidinger G, Moon RT (2003) When Wnts antagonize Wnts. J Cell Biol 162:753–755PubMedGoogle Scholar
  206. Weitzman JB (2005) Dishevelled nuclear shuttling. J Biol 4:1PubMedGoogle Scholar
  207. Westfall TA, Brimeyer R, Twedt J, Gladon J, Olberding A, Furutani-Seiki M, Slusarski DC (2003) Wnt-5/pipetail functions in vertebrate axis formation as a negative regulator of Wnt/beta-catenin activity. J Cell Biol 162:889–898PubMedGoogle Scholar
  208. Wharton KA Jr (2003) Runnin’ with the Dvl: proteins that associate with Dsh/Dvl and their significance to Wnt signal transduction. Dev Biol 253:1–17PubMedGoogle Scholar
  209. Willert K, Jones KA (2006) Wnt signaling: is the party in the nucleus? Genes Dev 20:1394–1404PubMedGoogle Scholar
  210. Willert K, Brown JD, Danenberg E, Duncan AW, Weissman IL, Reya T, Yates JR 3rd, Nusse R (2003) Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature 423:448–452PubMedGoogle Scholar
  211. Willinger T, Freeman T, Herbert M, Hasegawa H, McMichael AJ, Callan MF (2006) Human naive CD8 T cells down-regulate expression of the WNT pathway transcription factors lymphoid enhancer binding factor 1 and transcription factor 7 (T cell factor-1) following antigen encounter in vitro and in vivo. J Immunol 176:1439–1446PubMedGoogle Scholar
  212. Woodhead GJ, Mutch CA, Olson EC, Chenn A (2006) Cell-autonomous beta-catenin signaling regulates cortical precursor proliferation. J Neurosci 26:12620–12630PubMedGoogle Scholar
  213. Xu Q, Wang Y, Dabdoub A, Smallwood PM, Williams J, Woods C, Kelley MW, Jiang L, Tasman W, Zhang K, Nathans J (2004) Vascular development in the retina and inner ear: control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair. Cell 116:883–895PubMedGoogle Scholar
  214. Yabe D, Fukuda H, Aoki M, Yamada S, Takebayashi S, Shinkura R, Yamamoto N, Honjo T (2007) Generation of a conditional knockout allele for mammalian Spen protein Mint/SHARP. Genesis 45:300–306PubMedGoogle Scholar
  215. Yu JM, Kim JH, Song GS, Jung JS (2006) Increase in proliferation and differentiation of neural progenitor cells isolated from postnatal and adult mice brain by Wnt-3a and Wnt-5a. Mol Cell Biochem 288:17–28PubMedGoogle Scholar
  216. Zeng X, Tamai K, Doble B, Li S, Huang H, Habas R, Okamura H, Woodgett J, He X (2005) A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation. Nature 438:873–877PubMedGoogle Scholar
  217. Zhai L, Chaturvedi D, Cumberledge S (2004) Drosophila wnt-1 undergoes a hydrophobic modification and is targeted to lipid rafts, a process that requires porcupine. J Biol Chem 279:33220–33227PubMedGoogle Scholar
  218. Zhou CJ, Zhao C, Pleasure SJ (2004) Wnt signaling mutants have decreased dentate granule cell production and radial glial scaffolding abnormalities. J Neurosci 24:121–126PubMedGoogle Scholar
  219. Zhou CJ, Borello U, Rubenstein JL, Pleasure SJ (2006) Neuronal production and precursor proliferation defects in the neocortex of mice with loss of function in the canonical Wnt signaling pathway. Neuroscience 142:1119–1131PubMedGoogle Scholar
  220. Zorn AM, Barish GD, Williams BO, Lavender P, Klymkowsky MW, Varmus HE (1999) Regulation of Wnt signaling by Sox proteins: XSox17 alpha/beta and XSox3 physically interact with beta-catenin. Mol Cell 4:487–498PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  1. 1.GSF-National Research Center for Environment and Health, Institute of Developmental GeneticsMunich-NeuherbergGermany
  2. 2.Foundation for Research & Technology-Hellas, Biomedical Research InstituteUniversity of Ioannina, Science and Technology SchoolIoanninaGreece
  3. 3.Department of Biological Applications & TechnologyUniversity of Ioannina, Science and Technology SchoolIoanninaGreece

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