Genomes and Genes
Gene Symbol: Wnt1
Description: wingless-type MMTV integration site family, member 1
Alias: Int-1, Wnt-1, swaying, proto-oncogene Wnt-1, proto-oncogene Int-1, proto-oncogene protein Wnt-1, wingless-related MMTV integration site 1
- Zhao H, Cui Y, Dupont J, Sun H, Hennighausen L, Yakar S. Overexpression of the tumor suppressor gene phosphatase and tensin homologue partially inhibits wnt-1-induced mammary tumorigenesis. Cancer Res. 2005;65:6864-73 pubmed..This study identifies the PTEN as a therapeutic target for the treatment of mammary cancer and presumably other types of cancer. ..
- Smits S, Burbach J, Smidt M. Developmental origin and fate of meso-diencephalic dopamine neurons. Prog Neurobiol. 2006;78:1-16 pubmed..The data indicate that these specific subsets may explain the specific response of these neurons to toxins and genetic ablation. ..
- Dietrich P, Shanmugasundaram R, Shuyu E, Dragatsis I. Congenital hydrocephalus associated with abnormal subcommissural organ in mice lacking huntingtin in Wnt1 cell lineages. Hum Mol Genet. 2009;18:142-50 pubmed publisher..To further investigate the role of htt in these processes, we have inactivated the Hdh gene in Wnt1 cell lineages using the Cre-loxP system of recombination...
- Acampora D, Avantaggiato V, Tuorto F, Simeone A. Genetic control of brain morphogenesis through Otx gene dosage requirement. Development. 1997;124:3639-50 pubmed
- Teissedre B, PINDERHUGHES A, Incassati A, Hatsell S, Hiremath M, Cowin P. MMTV-Wnt1 and -DeltaN89beta-catenin induce canonical signaling in distinct progenitors and differentially activate Hedgehog signaling within mammary tumors. PLoS ONE. 2009;4:e4537 pubmed publisher..proportion of human breast cancer is associated with loss of secreted Wnt antagonists and mice expressing MMTV-Wnt1 and MMTV-DeltaN89beta-catenin develop mammary adenocarcinomas...
- Nichols D, Bruce L. Migratory routes and fates of cells transcribing the Wnt-1 gene in the murine hindbrain. Dev Dyn. 2006;235:285-300 pubmed..The present results will permit analyses of the effects of genetic manipulations on Wnt-1 lineage cells. ..
- Kato M, Patel M, Levasseur R, Lobov I, Chang B, Glass D, et al. Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor. J Cell Biol. 2002;157:303-14 pubmed..Moreover, these features recapitulate human osteoporosis-pseudoglioma syndrome, caused by LRP5 inactivation. ..
- Echelard Y, Vassileva G, McMahon A. Cis-acting regulatory sequences governing Wnt-1 expression in the developing mouse CNS. Development. 1994;120:2213-24 pubmed..In addition, transgene expression provides a new tool for the analysis of neural crest development in normal and mutant mouse embryos. ..
- Yang J, Brown A, Ellisor D, Paul E, Hagan N, Zervas M. Dynamic temporal requirement of Wnt1 in midbrain dopamine neuron development. Development. 2013;140:1342-52 pubmed publisherb>Wnt1-expressing progenitors generate midbrain dopamine (MbDA) and cerebellum (Cb) neurons in distinct temporal windows and from spatially discrete progenitor domains...
- Verani R, Cappuccio I, Spinsanti P, Gradini R, Caruso A, Magnotti M, et al. Expression of the Wnt inhibitor Dickkopf-1 is required for the induction of neural markers in mouse embryonic stem cells differentiating in response to retinoic acid. J Neurochem. 2007;100:242-50 pubmed..These data suggest that induction of Dkk-1 and the ensuing inhibition of the canonical Wnt pathway is required for neural differentiation of ES cells. ..
- Oshima H, Matsunaga A, Fujimura T, Tsukamoto T, Taketo M, Oshima M. Carcinogenesis in mouse stomach by simultaneous activation of the Wnt signaling and prostaglandin E2 pathway. Gastroenterology. 2006;131:1086-95 pubmed..We constructed K19-Wnt1 transgenic mice expressing Wnt1 in the gastric mucosa using the keratin 19 promoter...
- Nakajima M, Matsuda K, Miyauchi N, Fukunaga Y, Watanabe S, Okuyama S, et al. Hydrocephalus and abnormal subcommissural organ in mice lacking presenilin-1 in Wnt1 cell lineages. Brain Res. 2011;1382:275-81 pubmed publisher..To further investigate the role of PS1 in the brain, we inactivated the PS1 gene in Wnt1 cell lineages using the Cre-loxP recombination system...
- Brown A, Machan J, Hayes L, Zervas M. Molecular organization and timing of Wnt1 expression define cohorts of midbrain dopamine neuron progenitors in vivo. J Comp Neurol. 2011;519:2978-3000 pubmed publisher..MbDA neurons are generated from Wnt1-expressing progenitors located in the ventral mesencephalon (vMes) during embryogenesis...
- Barrott J, Cash G, Smith A, Barrow J, Murtaugh L. Deletion of mouse Porcn blocks Wnt ligand secretion and reveals an ectodermal etiology of human focal dermal hypoplasia/Goltz syndrome. Proc Natl Acad Sci U S A. 2011;108:12752-7 pubmed publisher..Conditional deletion of Porcn thus provides an experimental model of FDH, as well as a valuable tool to probe Wnt ligand function in vivo...
- Freyer L, Aggarwal V, Morrow B. Dual embryonic origin of the mammalian otic vesicle forming the inner ear. Development. 2011;138:5403-14 pubmed publisher..Using Wnt1-Cre, Pax3(Cre/+) and Hoxb1(Cre/+) mice to label and fate map cranial NEC lineages, we have demonstrated that cells ..
- Donehower L, Godley L, Aldaz C, Pyle R, Shi Y, Pinkel D, et al. Deficiency of p53 accelerates mammary tumorigenesis in Wnt-1 transgenic mice and promotes chromosomal instability. Genes Dev. 1995;9:882-95 pubmed..These findings favor a model in which p53 deficiency relaxes normal restraints on chromosomal number and organization during tumorigenesis. ..
- Danielian P, Muccino D, Rowitch D, Michael S, McMahon A. Modification of gene activity in mouse embryos in utero by a tamoxifen-inducible form of Cre recombinase. Curr Biol. 1998;8:1323-6 pubmed..Using the enhancer of the Wnt1 gene to restrict the expression of Cre-ERTM to the embryonic neural tube, we found that a single injection of ..
- Ellisor D, Koveal D, Hagan N, Brown A, Zervas M. Comparative analysis of conditional reporter alleles in the developing embryo and embryonic nervous system. Gene Expr Patterns. 2009;9:475-89 pubmed publisher..To assess the recombination/marking potential of the reporters, we utilized CreER(T) under the control of a Wnt1 transgene (Wnt1-CreER(T)) as well as a cumulative, non-inducible En1(Cre) knock-in line in combination with three ..
- Prakash N, Brodski C, Naserke T, Puelles E, Gogoi R, Hall A, et al. A Wnt1-regulated genetic network controls the identity and fate of midbrain-dopaminergic progenitors in vivo. Development. 2006;133:89-98 pubmed..The secreted glycoprotein Wnt1 is expressed in close vicinity to developing midbrain dopaminergic neurons...
- Li Y, Hively W, Varmus H. Use of MMTV-Wnt-1 transgenic mice for studying the genetic basis of breast cancer. Oncogene. 2000;19:1002-9 pubmed
- Mao B, Wu W, Li Y, Hoppe D, Stannek P, Glinka A, et al. LDL-receptor-related protein 6 is a receptor for Dickkopf proteins. Nature. 2001;411:321-5 pubmed..Thus, DKKs inhibit Wnt co-receptor function, exemplifying the modulation of LRP signalling by antagonists. ..
- Holmen S, Zylstra C, Mukherjee A, Sigler R, Faugere M, Bouxsein M, et al. Essential role of beta-catenin in postnatal bone acquisition. J Biol Chem. 2005;280:21162-8 pubmed..These findings suggest that Wnt/beta-catenin signaling in osteoblasts coordinates postnatal bone acquisition by controlling the differentiation and activity of both osteoblasts and osteoclasts. ..
- Chung S, Leung A, Han B, Chang M, Moon J, Kim C, et al. Wnt1-lmx1a forms a novel autoregulatory loop and controls midbrain dopaminergic differentiation synergistically with the SHH-FoxA2 pathway. Cell Stem Cell. 2009;5:646-58 pubmed publisher..In this study, we identified a novel Wnt1-Lmx1a autoregulatory loop during mDA differentiation of ESCs and confirmed its in vivo presence during embryonic ..
- Shimogori T, VanSant J, Paik E, Grove E. Members of the Wnt, Fz, and Frp gene families expressed in postnatal mouse cerebral cortex. J Comp Neurol. 2004;473:496-510 pubmed..Thus, canonical Wnt signaling could be utilized in a major cortical input by Fz- and Lef1-expressing thalamic cells that innervate the Wnt-expressing cortex. ..
- González Sancho J, Brennan K, Castelo Soccio L, Brown A. Wnt proteins induce dishevelled phosphorylation via an LRP5/6- independent mechanism, irrespective of their ability to stabilize beta-catenin. Mol Cell Biol. 2004;24:4757-68 pubmedWnt glycoproteins play essential roles in the development of metazoan organisms. Many Wnt proteins, such as Wnt1, activate the well-conserved canonical Wnt signaling pathway, which results in accumulation of beta-catenin in the cytosol ..
- Tang M, Villaescusa J, Luo S, Guitarte C, Lei S, Miyamoto Y, et al. Interactions of Wnt/beta-catenin signaling and sonic hedgehog regulate the neurogenesis of ventral midbrain dopamine neurons. J Neurosci. 2010;30:9280-91 pubmed publisher..Persistent activation of beta-catenin in early progenitors perturbs their cell cycle progression and antagonizes Shh expression, whereas activation of beta-catenin in midline progenitors promotes the generation of dopamine neurons. ..
- Zhang Y, Goss A, Cohen E, Kadzik R, Lepore J, Muthukumaraswamy K, et al. A Gata6-Wnt pathway required for epithelial stem cell development and airway regeneration. Nat Genet. 2008;40:862-70 pubmed publisher..Together, these data demonstrate that Gata6-regulated Wnt signaling controls the balance between progenitor expansion and epithelial differentiation required for both lung development and regeneration. ..
- Andl T, Reddy S, Gaddapara T, Millar S. WNT signals are required for the initiation of hair follicle development. Dev Cell. 2002;2:643-53 pubmed..This phenotype indicates that activation of WNT signaling in the skin precedes, and is required for, localized expression of regulatory genes and initiation of hair follicle placode formation. ..
- Chilov D, Sinjushina N, Saarimäki Vire J, Taketo M, Partanen J. beta-Catenin regulates intercellular signalling networks and cell-type specific transcription in the developing mouse midbrain-rhombomere 1 region. PLoS ONE. 2010;5:e10881 pubmed publisher..Interestingly, stabilization of beta-catenin rapidly caused down-regulation of the expression of Wnt1 itself, suggesting a negative feedback loop...
- Castelo Branco G, Wagner J, Rodriguez F, Kele J, Sousa K, Rawal N, et al. Differential regulation of midbrain dopaminergic neuron development by Wnt-1, Wnt-3a, and Wnt-5a. Proc Natl Acad Sci U S A. 2003;100:12747-52 pubmed..These findings indicate that Wnts are key regulators of proliferation and differentiation of DA precursors during VM neurogenesis and that different Wnts have specific and unique activity profiles. ..
- Perez Balaguer A, Puelles E, Wurst W, Martinez S. Shh dependent and independent maintenance of basal midbrain. Mech Dev. 2009;126:301-13 pubmed publisher..Based on our results and recently published data, we suggest the existence of a specific genetic pathway for the specification of the mesencephalic red nucleus. Foxa2 could be the candidate gene that might control this genetic pathway. ..
- Backman M, Machon O, Mygland L, van den Bout C, Zhong W, Taketo M, et al. Effects of canonical Wnt signaling on dorso-ventral specification of the mouse telencephalon. Dev Biol. 2005;279:155-68 pubmed..Thus, our data suggest that canonical Wnt signals are involved in maintaining the identity of the pallium by controlling expression of dorsal markers and by suppressing ventral programs from being activated in pallial progenitor cells. ..
- Bennett C, Longo K, Wright W, Suva L, Lane T, Hankenson K, et al. Regulation of osteoblastogenesis and bone mass by Wnt10b. Proc Natl Acad Sci U S A. 2005;102:3324-9 pubmed..Finally, Wnt10b-/- mice have decreased trabecular bone and serum osteocalcin, confirming that Wnt10b is an endogenous regulator of bone formation. ..
- Fischer T, Guimera J, Wurst W, Prakash N. Distinct but redundant expression of the Frizzled Wnt receptor genes at signaling centers of the developing mouse brain. Neuroscience. 2007;147:693-711 pubmed..b>Wnt1 secreted from the boundary between the mid- and hindbrain, for instance, controls the development of this brain ..
- Machon O, Backman M, Machonova O, Kozmik Z, Vacik T, Andersen L, et al. A dynamic gradient of Wnt signaling controls initiation of neurogenesis in the mammalian cortex and cellular specification in the hippocampus. Dev Biol. 2007;311:223-37 pubmed..This suggests that the dose of canonical Wnt signaling determines cellular fate in the developing cortex and hippocampus, and that recession of Wnt signaling acts as a morphogenetic gradient regulating neurogenesis in the cortex. ..
- Tanaka K, Okabayashi K, Asashima M, Perrimon N, Kadowaki T. The evolutionarily conserved porcupine gene family is involved in the processing of the Wnt family. Eur J Biochem. 2000;267:4300-11 pubmed..In transfected mammalian cells, all Mporc types affect the processing of mouse Wnt 1, 3A, 4, 6, and 7B but not 5A. Furthermore, all Mporc types are co-immunoprecipitated with various Wnt proteins...
- Wassarman K, Lewandoski M, Campbell K, Joyner A, Rubenstein J, Martinez S, et al. Specification of the anterior hindbrain and establishment of a normal mid/hindbrain organizer is dependent on Gbx2 gene function. Development. 1997;124:2923-34 pubmed..It is also required to maintain normal patterns of expression at the mid/hindbrain boundary of Fgf8 and Wnt1, genes that encode signaling molecules thought to be key components of the mid/hindbrain (isthmic) organizer...
- Andersson E, Salto C, Villaescusa J, Cajanek L, Yang S, Bryjova L, et al. Wnt5a cooperates with canonical Wnts to generate midbrain dopaminergic neurons in vivo and in stem cells. Proc Natl Acad Sci U S A. 2013;110:E602-10 pubmed publisher..Two of them, Wnt1 and Wnt5a, activate distinct branches of Wnt signaling and individually regulate different aspects of midbrain ..
- Bradbury J, Niemeyer C, Dale T, Edwards P. Alterations of the growth characteristics of the fibroblast cell line C3H 10T1/2 by members of the Wnt gene family. Oncogene. 1994;9:2597-603 pubmed..We conclude that at least some mesenchymal cells can respond to Wnt gene products. Our results are also the first report of biological effects of Wnt-6 and Wnt-7b. ..
- Tice D, Szeto W, Soloviev I, Rubinfeld B, Fong S, Dugger D, et al. Synergistic induction of tumor antigens by Wnt-1 signaling and retinoic acid revealed by gene expression profiling. J Biol Chem. 2002;277:14329-35 pubmed..In principal, the therapeutic index of antibodies directed against these antigens should be enhanced by co-administration of retinoic acid. ..
- Chi C, Martinez S, Wurst W, Martin G. The isthmic organizer signal FGF8 is required for cell survival in the prospective midbrain and cerebellum. Development. 2003;130:2633-44 pubmed..FGF8 and WNT1 have been implicated as key components of IsO signaling activity, and previous studies have shown that in Wnt1(-/-) ..
- Li J, Joyner A. Otx2 and Gbx2 are required for refinement and not induction of mid-hindbrain gene expression. Development. 2001;128:4979-91 pubmed..Furthermore, Otx2 and Gbx2 are required to suppress hindbrain and midbrain development, respectively, and thus allow establishment of the normal spatial domains of Fgf8 and other genes. ..
- Reddy S, Andl T, Bagasra A, Lu M, Epstein D, Morrisey E, et al. Characterization of Wnt gene expression in developing and postnatal hair follicles and identification of Wnt5a as a target of Sonic hedgehog in hair follicle morphogenesis. Mech Dev. 2001;107:69-82 pubmed..These results identify candidates for several key follicular signals and suggest that WNT and SHH signaling pathways interact to regulate hair follicle morphogenesis. ..
- van Noort M, Meeldijk J, van der Zee R, Destree O, Clevers H. Wnt signaling controls the phosphorylation status of beta-catenin. J Biol Chem. 2002;277:17901-5 pubmed..Immunohistochemical analysis of mouse embryos utilizing the antibody visualizes sites that transduce Wnt signals through the canonical Wnt cascade. ..
- Parr B, Shea M, Vassileva G, McMahon A. Mouse Wnt genes exhibit discrete domains of expression in the early embryonic CNS and limb buds. Development. 1993;119:247-61 pubmed..We discuss the significance of these patterns of restricted and partially overlapping domains of expression with respect to the putative function of Wnt signalling in early CNS and limb development. ..
- Mao J, Wang J, Liu B, Pan W, Farr G, Flynn C, et al. Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway. Mol Cell. 2001;7:801-9 pubmed..In addition, the LRP-5 sequences involved in interactions with Axin are required for LEF-1 activation. Thus, we conclude that the binding of Axin to LRP-5 is an important part of the Wnt signal transduction pathway. ..
- Tamai K, Semenov M, Kato Y, Spokony R, Liu C, Katsuyama Y, et al. LDL-receptor-related proteins in Wnt signal transduction. Nature. 2000;407:530-5 pubmed..The extracellular domain of LRP6 bound Wnt-1 and associated with Fz in a Wnt-dependent manner. Our results indicate that LRP6 may be a component of the Wnt receptor complex. ..
- Alvarez Medina R, Cayuso J, Okubo T, Takada S, Marti E. Wnt canonical pathway restricts graded Shh/Gli patterning activity through the regulation of Gli3 expression. Development. 2008;135:237-47 pubmed..Here, we show that Wnt1/Wnt3a, by signalling through the canonical beta-catenin/Tcf pathway, control expression of dorsal genes and ..
- Omodei D, Acampora D, Mancuso P, Prakash N, Di Giovannantonio L, Wurst W, et al. Anterior-posterior graded response to Otx2 controls proliferation and differentiation of dopaminergic progenitors in the ventral mesencephalon. Development. 2008;135:3459-70 pubmed publisher..Thus, our data provide new insights into the mechanism of mesDA neuron specification and suggest Otx2 as a potential target for cell replacement-based therapeutic approaches in PD. ..
- Hu H, Hilton M, Tu X, Yu K, Ornitz D, Long F. Sequential roles of Hedgehog and Wnt signaling in osteoblast development. Development. 2005;132:49-60 pubmed..Finally Wnt7b is identified as a potential endogenous ligand regulating osteogenesis. These data support a model that integrates Hh and Wnt signaling in the regulation of osteoblast development. ..
- Agalliu D, Takada S, Agalliu I, McMahon A, Jessell T. Motor neurons with axial muscle projections specified by Wnt4/5 signaling. Neuron. 2009;61:708-20 pubmed publisher..Thus, two dorsoventral signaling pathways, mediated by Shh and Wnt4/5, are required to establish an early binary divergence in motor neuron columnar identity. ..
- Pinson K, Brennan J, Monkley S, Avery B, Skarnes W. An LDL-receptor-related protein mediates Wnt signalling in mice. Nature. 2000;407:535-8 pubmed..Furthermore, we show a genetic enhancement of a Wnt mutant phenotype in mice lacking one functional copy of LRP6. Together, our results support a broad role for LRP6 in the transduction of several Wnt signals in mammals. ..
- Liu A, Losos K, Joyner A. FGF8 can activate Gbx2 and transform regions of the rostral mouse brain into a hindbrain fate. Development. 1999;126:4827-38 pubmed..In contrast, ectopic expression of Fgf8a in the mouse midbrain and caudal forebrain using a Wnt1 regulatory element produced no apparent patterning defects in the embryos examined (Lee, S. M., Danielian, P. S...
- Cajanek L, Ribeiro D, Liste I, Parish C, Bryja V, Arenas E. Wnt/beta-catenin signaling blockade promotes neuronal induction and dopaminergic differentiation in embryonic stem cells. Stem Cells. 2009;27:2917-27 pubmed publisher..One of the main regulators of DA neuron development is Wnt signaling. Here we used mouse ESCs (mESCs) lacking Wnt1 or the low-density lipoprotein receptor-related protein 6 (LRP6) to decipher the action of Wnt/beta-catenin ..
- Li Y, Welm B, Podsypanina K, Huang S, Chamorro M, Zhang X, et al. Evidence that transgenes encoding components of the Wnt signaling pathway preferentially induce mammary cancers from progenitor cells. Proc Natl Acad Sci U S A. 2003;100:15853-8 pubmed..Thus, the developmental heterogeneity of different breast cancers is in part a consequence of differential effects of oncogenes on distinct cell types in the breast...
- Bach A, Lallemand Y, Nicola M, Ramos C, Mathis L, Maufras M, et al. Msx1 is required for dorsal diencephalon patterning. Development. 2003;130:4025-36 pubmed..b>Wnt1 is essential for dorsoventral patterning of the neural tube...
- Lindvall C, Evans N, Zylstra C, Li Y, Alexander C, Williams B. The Wnt signaling receptor Lrp5 is required for mammary ductal stem cell activity and Wnt1-induced tumorigenesis. J Biol Chem. 2006;281:35081-7 pubmed..Here we have shown that mice deficient for the Wnt co-receptor Lrp5 are resistant to Wnt1-induced mammary tumors, which have been shown to be derived from the mammary stem/progenitor cell population...
- Bally Cuif L, Cholley B, Wassef M. Involvement of Wnt-1 in the formation of the mes/metencephalic boundary. Mech Dev. 1995;53:23-34 pubmed
- Brisken C, Heineman A, Chavarria T, Elenbaas B, Tan J, Dey S, et al. Essential function of Wnt-4 in mammary gland development downstream of progesterone signaling. Genes Dev. 2000;14:650-4 pubmed..Progesterone induces Wnt-4 in mammary epithelial cells and is required for increased Wnt-4 expression during pregnancy. Thus, Wnt signaling is essential in mediating progesterone function during mammary gland morphogenesis. ..
- Semenov M, Tamai K, Brott B, Kuhl M, Sokol S, He X. Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6. Curr Biol. 2001;11:951-61 pubmed..Our findings suggest that Wnt-Fz-LRP6 complex formation, but not Wnt-Fz interaction, triggers Wnt/beta-catenin signaling. ..
- Falk S, Wurdak H, Ittner L, Ille F, Sumara G, Schmid M, et al. Brain area-specific effect of TGF-beta signaling on Wnt-dependent neural stem cell expansion. Cell Stem Cell. 2008;2:472-83 pubmed publisher..In the midbrain, but not in the forebrain, Tgfbr2 ablation results in ectopic expression of Wnt1/beta-catenin and FGF8, activation of Wnt target genes, and increased proliferation and horizontal expansion of ..
- Cadigan K, Nusse R. Wnt signaling: a common theme in animal development. Genes Dev. 1997;11:3286-305 pubmed
- Ikeya M, Lee S, Johnson J, McMahon A, Takada S. Wnt signalling required for expansion of neural crest and CNS progenitors. Nature. 1997;389:966-70 pubmed..Given the widespread expression of different Wnt genes in discrete areas of the mammalian neural tube, this may represent a general model for the action of Wnt signalling in the developing CNS. ..
- Li J, Lao Z, Joyner A. Changing requirements for Gbx2 in development of the cerebellum and maintenance of the mid/hindbrain organizer. Neuron. 2002;36:31-43 pubmed..Our work has uncovered distinct requirements for Gbx2 during cerebellum formation and provided a model for how a transcription factor can play multiple roles during development. ..
- Blaess S, Corrales J, Joyner A. Sonic hedgehog regulates Gli activator and repressor functions with spatial and temporal precision in the mid/hindbrain region. Development. 2006;133:1799-809 pubmed..Thus, the precise spatial and temporal regulation of Gli2A and Gli3R by Shh is instrumental in coordinating mid/hindbrain development in three dimensions. ..