WNT and β-catenin signalling: diseases and therapies (original) (raw)

• Wodarz, A. & Nusse, R. Mechanisms of Wnt signaling in development. Annu. Rev. Cell Dev. Biol. 14, 59–88 (1998).
  Article CAS PubMed Google Scholar
• Huelsken, J. & Birchmeier, W. New aspects of Wnt signaling pathways in higher vertebrates. Curr. Opin. Genet. Dev. 11, 547–553 (2001).
  CAS PubMed Google Scholar
• Veeman, M. T., Axelrod, J. D. & Moon, R. T. A second canon. Functions and mechanisms of β-catenin-independent Wnt signaling. Dev. Cell 5, 367–377 (2003).
  CAS PubMed Google Scholar
• Tolwinski, N. S. & Wieschaus, E. Rethinking WNT signaling. Trends Genet. 20, 177–181 (2004).
  CAS PubMed Google Scholar
• Nelson, W. J. & Nusse, R. Convergence of Wnt, β-catenin, and cadherin pathways. Science 303, 1483–1487 (2004).
  CAS PubMed PubMed Central Google Scholar
• He, X., Semenov, M., Tamai, K. & Zeng, X. LDL receptor-related proteins 5 and 6 in Wnt/β-catenin signaling: arrows point the way. Development 131, 1663–1677 (2004).
  CAS PubMed Google Scholar
• Tan, C. et al. Inhibition of integrin linked kinase (ILK) suppresses β-catenin-Lef/Tcf-dependent transcription and expression of the E-cadherin repressor, snail, in APC−/− human colon carcinoma cells. Oncogene 20, 133–140 (2001).
  CAS PubMed Google Scholar
• Levina, E., Oren, M. & Ben-Ze'ev, A. Downregulation of β-catenin by p53 involves changes in the rate of β-catenin phosphorylation and Axin dynamics. Oncogene 23, 4444–4453 (2004).
  CAS PubMed Google Scholar
• Doble, B. W. & Woodgett, J. R. GSK-3: tricks of the trade for a multi-tasking kinase. J. Cell Sci. 116, 1175–1186 (2003).
  CAS PubMed Google Scholar
• Moon, R. T., Bowerman, B., Boutros, M. & Perrimon, N. The promise and perils of Wnt signaling through β-catenin. Science 296, 1644–1646 (2002).
  CAS PubMed Google Scholar
• Westfall, T. A. et al. Wnt-5/pipetail functions in vertebrate axis formation as a negative regulator of Wnt/β-catenin activity. J. Cell Biol. 162, 889–898 (2003).
  CAS PubMed PubMed Central Google Scholar
• Topol, L. et al. Wnt-5a inhibits the canonical Wnt pathway by promoting GSK-3-independent β-catenin degradation. J. Cell Biol. 162, 899–908 (2003).
  CAS PubMed PubMed Central Google Scholar
• Niemann, S. et al. Homozygous WNT3 mutation causes tetra-amelia in a large consanguineous family. Am. J. Hum. Genet. 74, 558–563 (2004).
  CAS PubMed PubMed Central Google Scholar
• Jordan, B. K., Shen, J. H., Olaso, R., Ingraham, H. A. & Vilain, E. Wnt4 overexpression disrupts normal testicular vasculature and inhibits testosterone synthesis by repressing steroidogenic factor 1/β-catenin synergy. Proc. Natl Acad. Sci. USA 100, 10866–10871 (2003).
  CAS PubMed PubMed Central Google Scholar
• Perantoni, A. O. Renal development: perspectives on a Wnt-dependent process. Semin. Cell Dev. Biol. 14, 201–208 (2003).
  CAS PubMed Google Scholar
• Terada, Y. et al. Expression and function of the developmental gene Wnt-4 during experimental acute renal failure in rats. J. Am. Soc. Nephrol. 14, 1223–1233 (2003).
  CAS PubMed Google Scholar
• Surendran, K. & Simon, T. C. CNP gene expression is activated by Wnt signaling and correlates with Wnt4 expression during renal injury. Am. J. Physiol. Renal Physiol. 284, F653–F562 (2003).
  CAS PubMed Google Scholar
• Rodova, M., Islam, M. R., Maser, R. L. & Calvet, J. P. The polycystic kidney disease-1 promoter is a target of the β-catenin/T-cell factor pathway. J. Biol. Chem. 277, 29577–29583 (2002).
  CAS PubMed Google Scholar
• Olson, D. J. & Gibo, D. M. Antisense wnt-5a mimics wnt-1-mediated C57MG mammary epithelial cell transformation. Exp. Cell Res. 241, 134–141 (1998).
  CAS PubMed Google Scholar
• Olson, D. J., Gibo, D. M., Saggers, G., Debinski, W. & Kumar, R. Reversion of uroepithelial cell tumorigenesis by the ectopic expression of human wnt-5a. Cell Growth Differ. 8, 417–423 (1997).
  CAS PubMed Google Scholar
• Liang, H. et al. Wnt5a inhibits B cell proliferation and functions as a tumor suppressor in hematopoietic tissue. Cancer Cell 4, 349–360 (2003). Strong evidence that WNT/calcium signalling is a tumour-suppressor pathway.
  CAS PubMed Google Scholar
• Weeraratna, A. T. et al. Wnt5a signaling directly affects cell motility and invasion of metastatic melanoma. Cancer Cell 1, 279–288 (2002). Solid evidence that WNT/calcium signalling is involved in metastasis.
  CAS PubMed Google Scholar
• Ouko, L., Ziegler, T. R., Gu, L. H., Eisenberg, L. M. & Yang, V. W. Wnt11 signaling promotes proliferation, transformation and migration of IEC6 intestinal epithelial cells. J. Biol. Chem. 279, 26707–26715 (2004).
  CAS PubMed Google Scholar
• Miyaoka, T., Seno, H. & Ishino, H. Increased expression of Wnt-1 in schizophrenic brains. Schizophr. Res. 38, 1–6 (1999).
  CAS PubMed Google Scholar
• Katsu, T. et al. The human frizzled-3 (FZD3) gene on chromosome 8p21, a receptor gene for Wnt ligands, is associated with the susceptibility to schizophrenia. Neurosci. Lett. 353, 53–56 (2003).
  CAS PubMed Google Scholar
• Kozlovsky, N., Belmaker, R. H. & Agam, G. GSK-3 and the neurodevelopmental hypothesis of schizophrenia. Eur. Neuropsychopharmacol. 12, 13–25 (2002).
  CAS PubMed Google Scholar
• Lijam, N. et al. Social interaction and sensorimotor gating abnormalities in mice lacking Dvl1. Cell 90, 895–905 (1997).
  CAS PubMed Google Scholar
• Loughlin, J. et al. Functional variants within the secreted frizzled-related protein 3 gene are associated with hip osteoarthritis in females. Proc. Natl Acad. Sci. USA 101, 9757–9762 (2004).
  CAS PubMed PubMed Central Google Scholar
• Easwaran, V. et al. β-catenin regulates vascular endothelial growth factor expression in colon cancer. Cancer Res. 63, 3145–3153 (2003).
  CAS PubMed Google Scholar
• Robitaille, J. et al. Mutant frizzled-4 disrupts retinal angiogenesis in familial exudative vitreoretinopathy. Nature Genet. 32, 326–330 (2002).
  CAS PubMed Google Scholar
• Toomes, C. et al. Mutations in LRP5 or FZD4 underlie the common familial exudative vitreoretinopathy locus on chromosome 11q. Am. J. Hum. Genet. 74, 721–730 (2004).
  CAS PubMed PubMed Central Google Scholar
• Kondo, H., Hayashi, H., Oshima, K., Tahira, T. & Hayashi, K. Frizzled 4 gene (FZD4) mutations in patients with familial exudative vitreoretinopathy with variable expressivity. Br. J. Ophthalmol. 87, 1291–1295 (2003).
  CAS PubMed PubMed Central Google Scholar
• Xu, Q. et al. Vascular development in the retina and inner ear: control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair. Cell 116, 883–895 (2004).
  CAS PubMed Google Scholar
• Kaykas, A. et al. Mutant Frizzled 4 associated with vitreoretinopathy traps wild-type Frizzled in the endoplasmic reticulum by oligomerization. Nature Cell Biol. 6, 52–58 (2004).
  CAS PubMed Google Scholar
• Harada, S. & Rodan, G. A. Control of osteoblast function and regulation of bone mass. Nature 423, 349–355 (2003).
  CAS PubMed Google Scholar
• Johnson, M. L. et al. Linkage of a gene causing high bone mass to human chromosome 11 (11q12-13). Am. J. Hum. Genet. 60, 1326–1332 (1997).
  CAS PubMed PubMed Central Google Scholar
• Little, R. D. et al. 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 (2002).
  CAS PubMed Google Scholar
• Boyden, L. M. et al. High bone density due to a mutation in LDL-receptor-related protein 5. N. Engl. J. Med. 346, 1513–1521 (2002).
  CAS PubMed Google Scholar
• Zhang, Y. et al. The LRP5 high-bone-mass G171V mutation disrupts LRP5 interaction with Mesd. Mol. Cell Biol. 24, 4677–4684 (2004).
  CAS PubMed PubMed Central Google Scholar
• Gong, Y. et al. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 107, 513–523 (2001). Evidence of LRP5 involvement in bone and eye formation.
  CAS PubMed Google Scholar
• Bodine, P. V. et al. The Wnt antagonist secreted frizzled-related protein-1 is a negative regulator of trabecular bone formation in adult mice. Mol. Endocrinol. 18, 1222–1237 (2004).
  CAS PubMed Google Scholar
• Kahler, R. A. & Westendorf, J. J. Lymphoid enhancer factor-1 and β-catenin inhibit Runx2-dependent transcriptional activation of the osteocalcin promoter. J. Biol. Chem. 278, 11937–11944 (2003).
  CAS PubMed Google Scholar
• Morin, P. J. & Weeraratna, A. T. Wnt signaling in human cancer. Cancer Treat. Res. 115, 169–187 (2003).
  CAS PubMed Google Scholar
• Taketo, M. M. Shutting down Wnt signal-activated cancer. Nature Genet. 36, 320–322 (2004).
  CAS PubMed Google Scholar
• Giles, R. H., van Es, J. H. & Clevers, H. Caught up in a Wnt storm: Wnt signaling in cancer. Biochim. Biophys. Acta 1653, 1–24 (2003).
  CAS PubMed Google Scholar
• van de Wetering, M. et al. The β-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell 111, 241–250 (2002).
  CAS PubMed Google Scholar
• Uematsu, K. et al. Activation of the Wnt pathway in non small cell lung cancer: evidence of dishevelled overexpression. Oncogene 22, 7218–7221 (2003).
  CAS PubMed Google Scholar
• Kim, J. S., Crooks, H., Foxworth, A. & Waldman, T. Proof-of-principle: oncogenic β-catenin is a valid molecular target for the development of pharmacological inhibitors. Mol. Cancer Ther. 1, 1355–1359 (2002).
  CAS PubMed Google Scholar
• Gunther, E. J. et al. Impact of p53 loss on reversal and recurrence of conditional Wnt-induced tumorigenesis. Genes Dev. 17, 488–501 (2003).
  CAS PubMed PubMed Central Google Scholar
• Derksen, P. W. et al. Illegitimate WNT signaling promotes proliferation of multiple myeloma cells. Proc. Natl Acad. Sci. USA 101, 6122–6127 (2004).
  CAS PubMed PubMed Central Google Scholar
• Suzuki, H. et al. Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer. Nature Genet. 36, 417–422 (2004).
  CAS PubMed Google Scholar
• Kratochwil, K., Galceran, J., Tontsch, S., Roth, W. & Grosschedl, R. FGF4, a direct target of LEF1 and Wnt signaling, can rescue the arrest of tooth organogenesis in Lef1 −/− mice. Genes Dev. 16, 3173–3185 (2002).
  CAS PubMed PubMed Central Google Scholar
• Lammi, L. et al. Mutations in AXIN2 cause familial tooth agenesis and predispose to colorectal cancer. Am. J. Hum. Genet. 74, 1043–1050 (2004).
  CAS PubMed PubMed Central Google Scholar
• Mak, B. C., Takemaru, K., Kenerson, H. L., Moon, R. T. & Yeung, R. S. The tuberin-hamartin complex negatively regulates β-catenin signaling activity. J. Biol. Chem. 278, 5947–5951 (2003).
  CAS PubMed Google Scholar
• Fuchs, E., Tumbar, T. & Guasch, G. Socializing with the neighbors: stem cells and their niche. Cell 116, 769–778 (2004).
  CAS PubMed Google Scholar
• Chang, C. H. et al. Distinct Wnt members regulate the hierarchical morphogenesis of skin regions (spinal tract) and individual feathers. Mech. Dev. 121, 157–171 (2004).
  CAS PubMed PubMed Central Google Scholar
• Zhu, A. J. & Watt, F. M. β-catenin signalling modulates proliferative potential of human epidermal keratinocytes independently of intercellular adhesion. Development 126, 2285–2298 (1999).
  CAS PubMed Google Scholar
• Chan, E. F., Gat, U., McNiff, J. M. & Fuchs, E. A common human skin tumour is caused by activating mutations in β-catenin. Nature Genet. 21, 410–413 (1999).
  CAS PubMed Google Scholar
• Guo, N., Hawkins, C. & Nathans, J. From the cover: Frizzled6 controls hair patterning in mice. Proc. Natl Acad. Sci. USA 101, 9277–9281 (2004).
  CAS PubMed PubMed Central Google Scholar
• Cheon, S. S. et al. β-catenin stabilization dysregulates mesenchymal cell proliferation, motility, and invasiveness and causes aggressive fibromatosis and hyperplastic cutaneous wounds. Proc. Natl Acad. Sci. USA 99, 6973–6978 (2002).
  CAS PubMed PubMed Central Google Scholar
• Cheon, S. S., Nadesan, P., Poon, R. & Alman, B. A. Growth factors regulate β-catenin-mediated TCF-dependent transcriptional activation in fibroblasts during the proliferative phase of wound healing. Exp. Cell Res. 293, 267–274 (2004).
  CAS PubMed Google Scholar
• Varallo, V. M. et al. β-catenin expression in Dupuytren's disease: potential role for cell-matrix interactions in modulating β-catenin levels in vivo and in vitro. Oncogene 22, 3680–3684 (2003).
  CAS PubMed Google Scholar
• Morrisey, E. E. Wnt signaling and pulmonary fibrosis. Am. J. Pathol. 162, 1393–1397 (2003).
  CAS PubMed PubMed Central Google Scholar
• Mucenski, M. L. et al. β-catenin is required for specification of proximal/distal cell fate during lung morphogenesis. J. Biol. Chem. 278, 40231–40238 (2003).
  CAS PubMed Google Scholar
• Chilosi, M. et al. Aberrant Wnt/β-catenin pathway activation in idiopathic pulmonary fibrosis. Am. J. Pathol. 162, 1495–1502 (2003).
  CAS PubMed PubMed Central Google Scholar
• Okubo, T. & Hogan, B. L. Hyperactive Wnt signaling changes the developmental potential of embryonic lung endoderm. J. Biol. 3, 11 (2004).
  PubMed PubMed Central Google Scholar
• Hardy, J. & Selkoe, D. J. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297, 353–356 (2002).
  CAS PubMed Google Scholar
• Terry, A. V. & Buccafusco, J. J. The cholinergic hypothesis of age and Alzheimer's disease-related cognitive deficits: recent challenges and their implications for novel drug development. J. Pharmacol. Exp. Ther. 306, 821–827 (2003).
  CAS PubMed Google Scholar
• Zhang, Z. et al. Destabilization of β-catenin by mutations in presenilin-1 potentiates neuronal apoptosis. Nature 395, 698–702 (1998).
  CAS PubMed Google Scholar
• Nishimura, M. et al. Presenilin mutations associated with Alzheimer disease cause defective intracellular trafficking of β-catenin, a component of the presenilin protein complex. Nature Med. 5, 164–169 (1999).
  CAS PubMed Google Scholar
• Takashima, A. et al. Presenilin 1 associates with glycogen synthase kinase-3β and its substrate tau. Proc. Natl Acad. Sci. USA 95, 9637–9641 (1998).
  CAS PubMed PubMed Central Google Scholar
• De Ferrari, G. V. & Inestrosa, N. C. Wnt signaling function in Alzheimer's disease. Brain Res. Brain Res. Rev. 33, 1–12 (2000).
  CAS PubMed Google Scholar
• Kang, D. E. et al. Presenilin couples the paired phosphorylation of β-catenin independent of axin: implications for β-catenin activation in tumorigenesis. Cell 110, 751–762 (2002).
  CAS PubMed Google Scholar
• Mudher, A. & Lovestone, S. Alzheimer's disease — do tauists and baptists finally shake hands? Trends Neurosci. 25, 22–26 (2002).
  CAS PubMed Google Scholar
• Caricasole, A. et al. The Wnt pathway, cell-cycle activation and β-amyloid: novel therapeutic strategies in Alzheimer's disease? Trends Pharmacol. Sci. 24, 233–238 (2003).
  CAS PubMed Google Scholar
• Mudher, A. et al. Dishevelled regulates the metabolism of amyloid precursor protein via protein kinase C/mitogen-activated protein kinase and c-Jun terminal kinase. J. Neurosci. 21, 4987–4995 (2001).
  CAS PubMed PubMed Central Google Scholar
• Alvarez, G. et al. Lithium protects cultured neurons against β-amyloid-induced neurodegeneration. FEBS Lett. 453, 260–264 (1999).
  CAS PubMed Google Scholar
• De Ferrari, G. V. et al. Activation of Wnt signaling rescues neurodegeneration and behavioral impairments induced by β-amyloid fibrils. Mol. Psychiatry 8, 195–208 (2003). Evidence that activating WNT/β-catenin signalling is neuroprotective in vitro and in vivo.
  CAS PubMed Google Scholar
• Phiel, C. J., Wilson, C. A., Lee, V. M. & Klein, P. S. GSK-3α regulates production of Alzheimer's disease amyloid-β peptides. Nature 423, 435–439 (2003).
  CAS PubMed Google Scholar
• Sun, X. et al. Lithium inhibits amyloid secretion in COS7 cells transfected with amyloid precursor protein C100. Neurosci. Lett. 321, 61–64 (2002).
  CAS PubMed Google Scholar
• Olson, E. N. & Schneider, M. D. Sizing up the heart: development redux in disease. Genes Dev. 17, 1937–1956 (2003).
  CAS PubMed Google Scholar
• Nakamura, T., Sano, M., Songyang, Z. & Schneider, M. D. A Wnt- and β-catenin-dependent pathway for mammalian cardiac myogenesis. Proc. Natl Acad. Sci. USA 100, 5834–5839 (2003).
  CAS PubMed PubMed Central Google Scholar
• Pandur, P., Lasche, M., Eisenberg, L. M. & Kuhl, M. Wnt-11 activation of a non-canonical Wnt signalling pathway is required for cardiogenesis. Nature 418, 636–641 (2002).
  CAS PubMed Google Scholar
• van Gijn, M. E., Daemen, M. J., Smits, J. F. & Blankesteijn, W. M. The wnt-frizzled cascade in cardiovascular disease. Cardiovasc. Res. 55, 16–24 (2002).
  CAS PubMed Google Scholar
• Barandon, L. et al. Reduction of infarct size and prevention of cardiac rupture in transgenic mice overexpressing FrzA. Circulation 108, 2282–2289 (2003).
  CAS PubMed Google Scholar
• Lepourcelet, M. et al. Small-molecule antagonists of the oncogenic Tcf/β-catenin protein complex. Cancer Cell 5, 91–102 (2004).
  CAS PubMed Google Scholar
• Emami, K. H. et al. A small molecule inhibitor of β-catenin/CBP transcription. Proc. Natl Acad. Sci. USA (in the press). New lead anti-cancer compound that blocks the WNT/β-catenin pathway.
• He, B. et al. A monoclonal antibody against Wnt-1 induces apoptosis in human cancer cells. Neoplasia 6, 7–14 (2004).
  CAS PubMed PubMed Central Google Scholar
• You, L. et al. Inhibition of Wnt-2-mediated signaling induces programmed cell death in non-small-cell lung cancer cells. Oncogene 21 June 2004 [epub ahead of print].
• Chakrabarty, S., Radjendirane, V., Appelman, H. & Varani, J. Extracellular calcium and calcium sensing receptor function in human colon carcinomas: promotion of E-cadherin expression and suppression of β-catenin/TCF activation. Cancer Res. 63, 67–71 (2003).
  CAS PubMed Google Scholar
• Boon, E. M. et al. Sulindac targets nuclear β-catenin accumulation and Wnt signalling in adenomas of patients with familial adenomatous polyposis and in human colorectal cancer cell lines. Br. J. Cancer 90, 224–229 (2004).
  CAS PubMed PubMed Central Google Scholar
• Dihlmann, S., Klein, S. & Doeberitz, M. K. Reduction of β-catenin/T-cell transcription factor signaling by aspirin and indomethacin is caused by an increased stabilization of phosphorylated β-catenin. Mol. Cancer Ther. 2, 509–516 (2003).
  CAS PubMed Google Scholar
• Nath, N., Kashfi, K., Chen, J. & Rigas, B. Nitric oxide-donating aspirin inhibits β-catenin/T cell factor (TCF) signaling in SW480 colon cancer cells by disrupting the nuclear β-catenin-TCF association. Proc. Natl Acad. Sci. USA 100, 12584–12589 (2003).
  CAS PubMed PubMed Central Google Scholar
• Lu, D. et al. Activation of the Wnt signaling pathway in chronic lymphocytic leukemia. Proc. Natl Acad. Sci. USA 101, 3118–3123 (2004).
  CAS PubMed PubMed Central Google Scholar
• Thompson, W. J. et al. Exisulind induction of apoptosis involves guanosine 3′,5′-cyclic monophosphate phosphodiesterase inhibition, protein kinase G activation, and attenuated β-catenin. Cancer Res. 60, 3338–3342 (2000).
  CAS PubMed Google Scholar
• Zhou, L. et al. Tyrosine kinase inhibitor STI-571/Gleevec downregulates the β-catenin signaling activity. Cancer Lett. 193, 161–170 (2003).
  CAS PubMed PubMed Central Google Scholar
• Suksaweang, S. et al. Morphogenesis of chicken liver: identification of localized growth zones and the role of β-catenin/Wnt in size regulation. Dev. Biol. 266, 109–122 (2004).
  CAS PubMed PubMed Central Google Scholar
• Chenn, A. & Walsh, C. A. Regulation of cerebral cortical size by control of cell cycle exit in neural precursors. Science 297, 365–369 (2002).
  CAS PubMed Google Scholar
• Ross, S. E. et al. Inhibition of adipogenesis by Wnt signaling. Science 289, 950–953 (2000).
  CAS PubMed Google Scholar
• Kielman, M. F. et al. Apc modulates embryonic stem-cell differentiation by controlling the dosage of β-catenin signaling. Nature Genet. 32, 594–605 (2002).
  CAS PubMed Google Scholar
• Kubo, F., Takeichi, M. & Nakagawa, S. Wnt2b controls retinal cell differentiation at the ciliary marginal zone. Development 130, 587–598 (2003).
  CAS PubMed Google Scholar
• Sato, N., Meijer, L., Skaltsounis, L., Greengard, P. & Brivanlou, A. H. Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor. Nature Med. 10, 55–63 (2004).
  CAS PubMed Google Scholar
• Eaves, C. J. Manipulating hematopoietic stem cell amplification with Wnt. Nature Immunol. 4, 511–512 (2003).
  CAS Google Scholar
• Lee, H. Y. et al. Instructive role of Wnt/β-catenin in sensory fate specification in neural crest stem cells. Science 303, 1020–1023 (2004).
  CAS PubMed Google Scholar
• Liu, B. Y., McDermott, S. P., Khwaja, S. S. & Alexander, C. M. The transforming activity of Wnt effectors correlates with their ability to induce the accumulation of mammary progenitor cells. Proc. Natl Acad. Sci. USA 101, 4158–4163 (2004).
  CAS PubMed PubMed Central Google Scholar
• Polesskaya, A., Seale, P. & Rudnicki, M. A. Wnt signaling induces the myogenic specification of resident CD45+ adult stem cells during muscle regeneration. Cell 113, 841–852 (2003).
  CAS PubMed Google Scholar
• Reya, T. et al. A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature 423, 409–414 (2003).
  CAS PubMed Google Scholar
• Willert, K. et al. Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature 423, 448–452 (2003). Purification of WNTs and demonstration of their potential effects on stem cells.
  CAS PubMed Google Scholar
• Murdoch, B. et al. Wnt-5A augments repopulating capacity and primitive hematopoietic development of human blood stem cells in vivo. Proc. Natl Acad. Sci. USA 100, 3422–3427 (2003).
  CAS PubMed PubMed Central Google Scholar
• Castelo-Branco, G. et al. Differential regulation of midbrain dopaminergic neuron development by Wnt-1, Wnt-3a, and Wnt-5a. Proc. Natl Acad. Sci. USA 100, 12747–12752 (2003).
  CAS PubMed PubMed Central Google Scholar
• Korinek, V. et al. Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4. Nature Genet. 19, 379–383 (1998).
  CAS PubMed Google Scholar
• Kuhnert, F. et al. Essential requirement for Wnt signaling in proliferation of adult small intestine and colon revealed by adenoviral expression of Dickkopf-1. Proc. Natl Acad. Sci. USA 101, 266–271 (2004).
  CAS PubMed Google Scholar
• Kim, J. H. et al. Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease. Nature 418, 50–56 (2002).
  CAS PubMed Google Scholar
• Hori, Y. et al. Growth inhibitors promote differentiation of insulin-producing tissue from embryonic stem cells. Proc. Natl Acad. Sci. USA 99, 16105–16110 (2002).
  CAS PubMed PubMed Central Google Scholar