To see the other types of publications on this topic, follow the link: Wnt genes.
Journal articles on the topic 'Wnt genes'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Wnt genes.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Nusse, Roel, and Harold E. Varmus. "Wnt genes." Cell 69, no. 7 (June 1992): 1073–87. http://dx.doi.org/10.1016/0092-8674(92)90630-u.
Full text
2
Parr, Brian A., and Andrew P. McMahon. "Wnt genes and vertebrate development." Current Opinion in Genetics & Development 4, no. 4 (August 1994): 523–28. http://dx.doi.org/10.1016/0959-437x(94)90067-d.
Full text
3
Brueggmann, Doerthe, Jenny M. Jaque, Celeste Leigh Pearce, and Claire Templeman. "Expression of Wnt-Signaling Pathway Genes and Wnt-Target Genes in Human Endometriosis Tissue [25]." Obstetrics & Gynecology 125 (May 2015): 18S. http://dx.doi.org/10.1097/01.aog.0000465314.25702.ef.
Full text
4
Girich, A. S., and A. V. Boyko. "Wnt and Frizzled Genes in Echinoderms." Russian Journal of Marine Biology 45, no. 4 (July 2019): 302–12. http://dx.doi.org/10.1134/s1063074019040072.
Full text
5
Hogvall, Mattias, Bruno C. Vellutini, José M. Martín-Durán, Andreas Hejnol, Graham E. Budd, and Ralf Janssen. "Embryonic expression of priapulid Wnt genes." Development Genes and Evolution 229, no. 4 (July 2019): 125–35. http://dx.doi.org/10.1007/s00427-019-00636-6.
Full text
6
Krauss, S., V. Korzh, A. Fjose, and T. Johansen. "Expression of four zebrafish wnt-related genes during embryogenesis." Development 116, no. 1 (September 1, 1992): 249–59. http://dx.doi.org/10.1242/dev.116.1.249.
Full textAbstract:
The wnt gene family codes for a group of cysteine-rich, secreted proteins, which are differentially expressed in the developing embryo and are possibly involved in cellular communication. Here, we describe the polymerase chain reaction based cloning and embryonic expression patterns of four zebrafish wnt-related sequences; wnt[a], wnt[b], wnt[c] and wnt[d]. One of these genes, wnt[a], is a potential homologue of murine Wnt-3, while the other three genes most likely represent new members of the vertebrate wnt gene family. In zebrafish embryos, transcripts of wnt[a] are confined to the dorsal diencephalon, the dorsal midbrain, the rhombic lips and the dorsal portions of the spinal cord. wnt[b] is expressed in the tail bud and at considerably lower levels in the mesoderm of the head. wnt[c] transcripts are present within the diencephalon and the posterior midbrain whereas wnt[d] shows a surprisingly similar expression pattern to zebrafish wnt-1. By analogy to wnt-1, it is likely that the members of the zebrafish wnt gene family play an important role in cell-to-cell signalling during pattern formation in the neural tube and the tail bud.
7
Wong, G. T., B. J. Gavin, and A. P. McMahon. "Differential transformation of mammary epithelial cells by Wnt genes." Molecular and Cellular Biology 14, no. 9 (September 1994): 6278–86. http://dx.doi.org/10.1128/mcb.14.9.6278.
Full textAbstract:
The mouse Wnt family includes at least 10 genes that encode structurally related secreted glycoproteins. Wnt-1 and Wnt-3 were originally identified as oncogenes activated by the insertion of mouse mammary tumor virus in virus-induced mammary adenocarcinomas, although they are not expressed in the normal mammary gland. However, five other Wnt genes are differentially expressed during development of adult mammary tissue, suggesting that they may play distinct roles in various phases of mammary gland growth and development. Induction of transformation by Wnt-1 and Wnt-3 may be due to interference with these normal regulatory events; however, there is no direct evidence for this hypothesis. We have tested Wnt family members for the ability to induce transformation of cultured mammary cells. The results demonstrate that the Wnt gene family can be divided into three groups depending on their ability to induce morphological transformation and altered growth characteristics of the C57MG mammary epithelial cell line. Wnt-1, Wnt-3A, and Wnt-7A were highly transforming and induced colonies which formed and shed balls of cells. Wnt-2, Wnt-5B, and Wnt-7B also induced transformation but with a lower frequency and an apparent decrease in saturation density. In contrast, Wnt-6 and two other family members which are normally expressed in C57MG cells, Wnt-4 and Wnt-5A, failed to induce transformation. These data demonstrate that the Wnt genes have distinct effects on cell growth and should not be regarded as functionally equivalent.
8
Wong, G. T., B. J. Gavin, and A. P. McMahon. "Differential transformation of mammary epithelial cells by Wnt genes." Molecular and Cellular Biology 14, no. 9 (September 1994): 6278–86. http://dx.doi.org/10.1128/mcb.14.9.6278-6286.1994.
Full textAbstract:
The mouse Wnt family includes at least 10 genes that encode structurally related secreted glycoproteins. Wnt-1 and Wnt-3 were originally identified as oncogenes activated by the insertion of mouse mammary tumor virus in virus-induced mammary adenocarcinomas, although they are not expressed in the normal mammary gland. However, five other Wnt genes are differentially expressed during development of adult mammary tissue, suggesting that they may play distinct roles in various phases of mammary gland growth and development. Induction of transformation by Wnt-1 and Wnt-3 may be due to interference with these normal regulatory events; however, there is no direct evidence for this hypothesis. We have tested Wnt family members for the ability to induce transformation of cultured mammary cells. The results demonstrate that the Wnt gene family can be divided into three groups depending on their ability to induce morphological transformation and altered growth characteristics of the C57MG mammary epithelial cell line. Wnt-1, Wnt-3A, and Wnt-7A were highly transforming and induced colonies which formed and shed balls of cells. Wnt-2, Wnt-5B, and Wnt-7B also induced transformation but with a lower frequency and an apparent decrease in saturation density. In contrast, Wnt-6 and two other family members which are normally expressed in C57MG cells, Wnt-4 and Wnt-5A, failed to induce transformation. These data demonstrate that the Wnt genes have distinct effects on cell growth and should not be regarded as functionally equivalent.
9
Jackstadt, Rene, Michael Charles Hodder, and Owen James Sansom. "WNT and β-Catenin in Cancer: Genes and Therapy." Annual Review of Cancer Biology 4, no. 1 (March 9, 2020): 177–96. http://dx.doi.org/10.1146/annurev-cancerbio-030419-033628.
Full textAbstract:
The WNT pathway is a pleiotropic signaling pathway that controls developmental processes, tissue homeostasis, and cancer. The WNT pathway is commonly mutated in many cancers, leading to widespread research into the role of WNT signaling in carcinogenesis. Understanding which cancers are reliant upon WNT activation and which components of the WNT signaling pathway are mutated is paramount to advancing therapeutic strategies. In addition, building holistic insights into the role of WNT signaling in not only tumor cells but also the tumor microenvironment is a vital area of research and may be a promising therapeutic strategy in multiple immunologically inert cancers. Novel compounds aimed at modulating the WNT signaling pathway using diverse mechanisms are currently under investigation in preclinical/early clinical studies. Here, we review how the WNT pathway is activated in multiple cancers and discuss current strategies to target aberrant WNT signaling.
10
Ding, Xin, Junxia Liu, Lu Zheng, Jiangbo Song, Niannian Li, Hai Hu, Xiaoling Tong, and Fangyin Dai. "Genome-Wide Identification and Expression Profiling of Wnt Family Genes in the Silkworm, Bombyx mori." International Journal of Molecular Sciences 20, no. 5 (March 11, 2019): 1221. http://dx.doi.org/10.3390/ijms20051221.
Full textAbstract:
Wnt is a family of conserved glycoproteins that participate in a variety of important biological processes including embryo development, cell proliferation and differentiation, and tissue regeneration. The Wnt family is a metazoan novelty found in all animal phyla. Studies have revealed that the number of Wnt genes varies among species, presumably due to reproduction and loss of genes during evolution. However, a comprehensive inventory of Wnt genes in Lepidoptera is lacking. In this study, we identified the repertoire of Wnt genes in the silkworm and seven other species of Lepidoptera and obtained eight Wnt genes (Wnt1, Wnt5–Wnt7, Wnt9–Wnt11, and WntA) in each species. Four of these Wnt genes are clustered in two orientations (5′-Wnt9-Wnt1-Wnt6-Wnt10-3′ and 5′-Wnt10-Wnt6-Wnt1-Wnt9-3′) in both moths and butterflies. Transcript analysis of Wnt in silkworm embryonic stages showed that each BmWnt gene had a unique expression pattern during embryological development. Analysis of a larval stage revealed differential expression of Wnt family members in diverse tissues. Our study provides an overview of the Wnt family in Lepidoptera and will inspire further functional study of the Wnt genes in the silkworm.
11
Ramakrishnan, Aravinda-Bharathi, and Ken M. Cadigan. "Wnt target genes and where to find them." F1000Research 6 (May 24, 2017): 746. http://dx.doi.org/10.12688/f1000research.11034.1.
Full textAbstract:
Wnt/β-catenin signaling is highly conserved throughout metazoans, is required for numerous essential events in development, and serves as a stem cell niche signal in many contexts. Misregulation of the pathway is linked to several human pathologies, most notably cancer. Wnt stimulation results in stabilization and nuclear import of β-catenin, which then acts as a transcriptional co-activator. Transcription factors of the T-cell family (TCF) are the best-characterized nuclear binding partners of β-catenin and mediators of Wnt gene regulation. This review provides an update on what is known about the transcriptional activation of Wnt target genes, highlighting recent work that modifies the conventional model. Wnt/β-catenin signaling regulates genes in a highly context-dependent manner, and the role of other signaling pathways and TCF co-factors in this process will be discussed. Understanding Wnt gene regulation has served to elucidate many biological roles of the pathway, and we will use examples from stem cell biology, metabolism, and evolution to illustrate some of the rich Wnt biology that has been uncovered.
12
Khan, Naveed I., Kenneth Francis Bradstock, and Linda J. Bendall. "The Wnt Pathway Modulates Expression of Growth and Survival Genes in Acute Lymphoblastic Leukemia Cells." Blood 108, no. 11 (November 16, 2006): 1850. http://dx.doi.org/10.1182/blood.v108.11.1850.1850.
Full textAbstract:
Abstract Wnt proteins are important bone marrow-derived growth factors known to support normal hematopoietic progenitor and stem cell development. Here we report that B cell progenitor acute lymphoblastic leukemia (pre-B ALL) cells express Wnt proteins, including Wnt-2b in 33%, Wnt-5a in 42%, Wnt-10b in 58% and Wnt-16b in 25% of cases. The Wnt receptors, Frizzled (Fz)-7 and -8 were also expressed in most cases while Fz-3, -4 and -9 were occasionally detected. Stimulation of pre-B ALL cells with Wnt-3a activated canonical Wnt signaling with increased expression and nuclear translocation of β-catenin. This resulted in a 1.7 to 5.3-fold increase in cell proliferation, which was associated with enhanced cell cycle entry. Wnt-3a also significantly increased the survival of pre-B ALL cells under conditions of serum deprivation. To determine the mechanisms involved we examined the effects of Wnt-3a on gene expression using the leukemic pre-B ALL cell line NALM6 and a cancer specific microarray (GEArray® OHS-802), which contains 440 known cancer genes. Expression of 83 genes (19%) could be detected on the array. Exposure to Wnt-3a for 24 hours resulted in increased (>1.5 fold) expression of 29 genes and reduced (<50% of control) expression of 3 genes. The most highly regulated genes in response to Wnt-3a were MYBL2, E2F1, CD10, VDAC1, CDC25B (upregulated) and TRAIL-R2 (downregulated). Using qRT-PCR, we confirmed regulation of these genes in NALM6 cells and/or in another leukemic cell line LK63. These genes play important roles in the control of cell cycle (MYBL2, E2F1 and CDC25B), apoptosis (VDAC1 and TRAIL-R2) and motility (CD10) in cancer cells. Our results suggest that Wnt signalling regulates cell growth and proliferation in leukemic cells by modulating the expression of a number of genes. To our knowledge this is the first study examining the gene expression profile following Wnt stimulation in leukemic cells and potentially identifies new therapeutic targets for treatment.
13
Ambrosetti, Davide, Greg Holmes, Alka Mansukhani, and Claudio Basilico. "Fibroblast Growth Factor Signaling Uses Multiple Mechanisms To Inhibit Wnt-Induced Transcription in Osteoblasts." Molecular and Cellular Biology 28, no. 15 (May 22, 2008): 4759–71. http://dx.doi.org/10.1128/mcb.01849-07.
Full textAbstract:
ABSTRACT Fibroblast growth factor (FGF) and Wnt signals are both critical for proper bone development. We previously reported that the expression of activating FGF receptor mutations in osteoblasts downregulated the expression of many genes reported as targets of Wnt signaling, suggesting an antagonistic effect between Wnt signaling, which promotes osteoblast differentiation and function, and FGF signaling, which inhibits these processes. To analyze the effect of FGF on Wnt signaling in osteoblasts, we created reporter cell lines where a Wnt-responsive promoter drives luciferase expression and showed that Wnt3a-induced luciferase expression was specifically inhibited by FGF treatment. FGF specifically prevented the formation of a Wnt-induced transcriptional complex of TCF1 and -4 with β-catenin on DNA. FGF did not significantly affect the activation of β-catenin, although it reduced both the expression of TCF/LEF factors and their induction by Wnt. Microarray analysis using osteoblasts treated with Wnt3a and FGF alone or in combination showed that about 70% of the genes induced by Wnt3a were downregulated by combined FGF treatment. These included novel and previously identified Wnt target genes and genes involved in osteoblast differentiation. Furthermore, FGF alone could downregulate the expression of four Fzd Wnt receptor genes. Our results show that FGF antagonizes Wnt signaling by inhibiting Wnt-induced transcription and suggest that multiple mechanisms, including downregulation of TCFs and Wnt receptors, contribute to this effect.
14
Caspi, Elanite, and Rina Rosin-Arbesfeld. "A Novel Functional Screen in Human Cells Identifies MOCA as a Negative Regulator of Wnt Signaling." Molecular Biology of the Cell 19, no. 11 (November 2008): 4660–74. http://dx.doi.org/10.1091/mbc.e07-10-1046.
Full textAbstract:
Aberrant Wnt signal transduction is involved in many human diseases such as cancer and neurodegenerative disorders. The key effector protein of the canonical Wnt pathway is β-catenin, which functions with T-cell factor/lymphoid enhancer factor (TCF/LEF) to activate gene transcription that leads to expression of Wnt target genes. In this study we provide results obtained from a novel functional screen of a human brain cDNA library used to identify 63 genes that are putative negative Wnt regulators. These genes were divided into eight functional groups that include known canonical and noncanonical Wnt pathway components and genes that had not yet been assigned to the Wnt pathway. One of the groups, the presenilin-binding proteins, contains the modifier of cell adhesion (MOCA) gene. We show that MOCA is a novel inhibitor of Wnt/β-catenin signaling. MOCA forms a complex with β-catenin and inhibits transcription of known Wnt target genes. Epistasis experiments indicate that MOCA acts to reduce the levels of nuclear β-catenin, increase the levels of membrane-bound β-catenin, and enhances cell–cell adhesion. Therefore, our data indicate that MOCA is a novel Wnt negative regulator and demonstrate that this screening approach can be a rapid means for isolation of new Wnt regulators.
15
Chim, C. S., R. Pang, and R. Liang. "Epigenetic dysregulation of the Wnt signalling pathway in chronic lymphocytic leukaemia." Journal of Clinical Pathology 61, no. 11 (September 2, 2008): 1214–19. http://dx.doi.org/10.1136/jcp.2008.060152.
Full textAbstract:
Background:Wnt signalling has recently been implicated in the pathogenesis of cancer.Methods:This study investigated the activity of Wnt signalling in peripheral blood chronic lymphocytic leukaemia (CLL) lymphocytes, and the methylation status of seven soluble Wnt antagonist genes, including WIF1, DKK3, APC, SFRP1, SFRP2, SFRP4 and SFRP5, by using methylation-specific PCR in the peripheral blood CLL lymphocytes and bone marrow samples of patients with CLL at diagnosis.Results:In the peripheral blood CLL lymphocytes, constitutive activation of Wnt signalling was detected, associated with hypermethylation of the soluble Wnt inhibitor genes. In the diagnostic CLL marrow samples, methylation of the seven genes was detected in up to 36.4% of samples. Moreover, 23 (52.3%) patients had methylation of at least one of the seven genes, of whom 14 (60.8%) had methylation of two or more Wnt inhibitor genes. Apart from an association of advanced age with DKK3 methylation, there was no association of gene hypermethylation with either clinical characteristics (including age, gender, lymphocyte count at diagnosis, Rai stage and poor-risk karyotype) or survival.Conclusion:Wnt signalling is constitutively activated in CLL B lymphocytes in association with methylation of multiple soluble Wnt antagonist genes. Methylation of these soluble Wnt antagonist genes, occasionally multiple genes, in primary CLL marrow samples suggests an important role in CLL pathogenesis. Moreover, this study underscored the importance of studying methylation of a panel of, but not individual, genes regulating a cellular pathway.
16
Van Den Berg, David J., Arun K. Sharma, Edward Bruno, and Ron Hoffman. "Role of Members of the Wnt Gene Family in Human Hematopoiesis." Blood 92, no. 9 (November 1, 1998): 3189–202. http://dx.doi.org/10.1182/blood.v92.9.3189.
Full textAbstract:
Abstract The hematopoietic system is derived from ventral mesoderm. A number of genes that are important in mesoderm development have been identified including members of the transforming growth factor-β (TGF-β) superfamily, the fibroblast growth factor (FGF) family, and the Wnt gene family. Because TGF-β plays a pleiotropic role in hematopoiesis, we wished to determine if other genes that are important in mesoderm development, specifically members of theWnt gene family, may play a role in hematopoiesis. Three members of the Wnt gene family (Wnt-5A, Wnt-2B, and Wnt-10B) were identified and cloned from human fetal bone stromal cells. These genes are expressed to varying levels in hematopoietic cell lines derived from T cells, B cells, myeloid cells, and erythroid cells; however, only Wnt-5A was expressed in CD34+Lin− primitive progenitor cells. The in vitro biological activity of these Wnt genes on CD34+Lin− hematopoietic progenitors was determined in a feeder cell coculture system and assayed by quantitating progenitor cell numbers, CD34+ cell numbers, and numbers of differentiated cell types. The number of hematopoietic progenitor cells was markedly affected by exposure to stromal cell layers expressing Wnt genes with 10- to 20-fold higher numbers of mixed colony-forming units (CFU-MIX), 1.5- to 2.6-fold higher numbers of CFU-granulocyte macrophage (CFU-GM), and greater than 10-fold higher numbers of burst-forming units-erythroid (BFU-E) in the Wnt-expressing cocultures compared with the controls. Colony formation by cells expanded on theWnt-expressing cocultures was similar for each of the three genes, indicating similar action on primitive progenitor cells; however, Wnt-10B showed differential activity on erythroid progenitors (BFU-E) compared with Wnt-5A and Wnt-2B. Cocultures containing Wnt-10B alone or in combination with all three Wnt genes had threefold to fourfold lower BFU-E colony numbers than the Wnt-5A– or Wnt-2B–expressing cocultures. The frequency of CD34+ cells was higher inWnt-expressing cocultures and cellular morphology indicated that coculture in the presence of Wnt genes resulted in higher numbers of less differentiated hematopoietic cells and fewer mature cells than controls. These data indicate that the gene products of theWnt family function as hematopoietic growth factors, and that they may exhibit higher specificity for earlier progenitor cells. © 1998 by The American Society of Hematology.
17
Van Den Berg, David J., Arun K. Sharma, Edward Bruno, and Ron Hoffman. "Role of Members of the Wnt Gene Family in Human Hematopoiesis." Blood 92, no. 9 (November 1, 1998): 3189–202. http://dx.doi.org/10.1182/blood.v92.9.3189.421k45_3189_3202.
Full textAbstract:
The hematopoietic system is derived from ventral mesoderm. A number of genes that are important in mesoderm development have been identified including members of the transforming growth factor-β (TGF-β) superfamily, the fibroblast growth factor (FGF) family, and the Wnt gene family. Because TGF-β plays a pleiotropic role in hematopoiesis, we wished to determine if other genes that are important in mesoderm development, specifically members of theWnt gene family, may play a role in hematopoiesis. Three members of the Wnt gene family (Wnt-5A, Wnt-2B, and Wnt-10B) were identified and cloned from human fetal bone stromal cells. These genes are expressed to varying levels in hematopoietic cell lines derived from T cells, B cells, myeloid cells, and erythroid cells; however, only Wnt-5A was expressed in CD34+Lin− primitive progenitor cells. The in vitro biological activity of these Wnt genes on CD34+Lin− hematopoietic progenitors was determined in a feeder cell coculture system and assayed by quantitating progenitor cell numbers, CD34+ cell numbers, and numbers of differentiated cell types. The number of hematopoietic progenitor cells was markedly affected by exposure to stromal cell layers expressing Wnt genes with 10- to 20-fold higher numbers of mixed colony-forming units (CFU-MIX), 1.5- to 2.6-fold higher numbers of CFU-granulocyte macrophage (CFU-GM), and greater than 10-fold higher numbers of burst-forming units-erythroid (BFU-E) in the Wnt-expressing cocultures compared with the controls. Colony formation by cells expanded on theWnt-expressing cocultures was similar for each of the three genes, indicating similar action on primitive progenitor cells; however, Wnt-10B showed differential activity on erythroid progenitors (BFU-E) compared with Wnt-5A and Wnt-2B. Cocultures containing Wnt-10B alone or in combination with all three Wnt genes had threefold to fourfold lower BFU-E colony numbers than the Wnt-5A– or Wnt-2B–expressing cocultures. The frequency of CD34+ cells was higher inWnt-expressing cocultures and cellular morphology indicated that coculture in the presence of Wnt genes resulted in higher numbers of less differentiated hematopoietic cells and fewer mature cells than controls. These data indicate that the gene products of theWnt family function as hematopoietic growth factors, and that they may exhibit higher specificity for earlier progenitor cells. © 1998 by The American Society of Hematology.
18
Lu, C., D. Shah, A. Wijnands, B. Oldenburg, W. C. Yeh, G. Vanhove, and Y. Li. "P085 Expression profiling of Wnt pathway genes in colon biopsies of patients with Ulcerative Colitis." Journal of Crohn's and Colitis 15, Supplement_1 (May 1, 2021): S186. http://dx.doi.org/10.1093/ecco-jcc/jjab076.214.
Full textAbstract:
Abstract Background There is an increasing demand of agents that can promote mucosal healing in Inflammatory Bowel Disease (IBD). Wnt/β-catenin signaling plays a critical role in epithelial regeneration and repair, and stimulating regeneration in the damaged epithelium by modulating Wnt signaling has been suggested as a potential treatment option for IBD. To guide development of Wnt modulating therapeutic molecules for IBD, an understanding of how Wnt signaling may be altered in IBD tissues is required. While earlier work showed altered Wnt pathway gene expression in UC tissues, these studies failed to consider disease conditions (moderate vs severe) and patient treatment history on expression of the Wnt family genes. These previous studies utilized RT-qPCR or microarray and did not reveal how Wnt pathway gene expression might be affected specifically in the epithelium and in the adjacent stromal stem cell niche. Here we report our work investigating expression patterns of Wnt pathway genes in UC biopsies from 12 patients with moderate and severe disease. Patients had either received no anti-TNF treatment or had gone through anti-TNF treatment and partially responded to the treatment. Methods Expression of a set of Wnt pathway genes was assessed in UC colon and rectum biopsies by RNAscope in situ hybridization and compared to expression patterns in normal control colon. The genes included the Wnt target genes AXIN2, LGR5 and RNF43, Wnt ligands and the FZD5 and LRP6 receptors enriched in the intestinal epithelium as well as key Wnt signal modulators RSPO1-4. Results Expression of Wnt target genes were mildly reduced in the UC colon epithelium, while their expression in some crypts appeared much lower. Overall expression levels of Wnt pathway genes did not differ between moderate and severe UC colon and Wnt target gene expression was more affected in the anti-TNF treated colons, which may reflect more refractory disease. Expression of FZD5, LRP6 and the key niche factor RSPO2, was reduced in the UC colon. RSPOs are normally expressed in the stromal cells next to the crypt bottom stem cell compartment but this expression pattern was disrupted in the UC colon as a result of immune cell infiltration. Although expression of Wnts was induced in the UC colon tissues, the location of expression was altered due to tissue damage, potentially making the Wnts less accessible to the intestinal stem cells. Conclusion Reduced expression of Wnt receptors, RSPOs and Wnt target genes indicate insufficient Wnt signal induction in the damaged colon epithelium of UC patients. This suggests that repair of the damaged epithelium by Wnt agonist treatment may constitute a new mechanism of action and benefit patients with UC.
19
Parr, B. A., M. J. Shea, G. Vassileva, and A. P. McMahon. "Mouse Wnt genes exhibit discrete domains of expression in the early embryonic CNS and limb buds." Development 119, no. 1 (September 1, 1993): 247–61. http://dx.doi.org/10.1242/dev.119.1.247.
Full textAbstract:
Mutation and expression studies have implicated the Wnt gene family in early developmental decision making in vertebrates and flies. In a detailed comparative analysis, we have used in situ hybridization of 8.0- to 9.5-day mouse embryos to characterize expression of all ten published Wnt genes in the central nervous system (CNS) and limb buds. Seven of the family members show restricted expression patterns in the brain. At least three genes (Wnt-3, Wnt-3a, and Wnt-7b) exhibit sharp boundaries of expression in the forebrain that may predict subdivisions of the region later in development. In the spinal cord, Wnt-1, Wnt-3, and Wnt-3a are expressed dorsally, Wnt-5a, Wnt-7a, and Wnt-7b more ventrally, and Wnt-4 both dorsally and in the floor plate. In the forelimb primordia, Wnt-3, Wnt-4, Wnt-6 and Wnt-7b are expressed fairly uniformly throughout the limb ectoderm. Wnt-5a RNA is distributed in a proximal to distal gradient through the limb mesenchyme and ectoderm. Along the limb's dorsal-ventral axis, Wnt-5a is expressed in the ventral ectoderm and Wnt-7a in the dorsal ectoderm. 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.
20
Dickinson, Mary E., and Andrew P. McMahon. "The role of Wnt genes in vertebrate development." Current Opinion in Genetics & Development 2, no. 4 (January 1992): 562–66. http://dx.doi.org/10.1016/s0959-437x(05)80172-8.
Full text
21
Lloyd, Susan, Tom P. Fleming, and Jane E. Collins. "Expression of Wnt genes during mouse preimplantation development." Gene Expression Patterns 3, no. 3 (June 2003): 309–12. http://dx.doi.org/10.1016/s1567-133x(03)00046-2.
Full text
22
Dimitriadis, Anna, Elizabeth Vincan, Idris M. Mohammed, Nandor Roczo, Wayne A. Phillips, and Swati Baindur-Hudson. "Expression of Wnt genes in human colon cancers." Cancer Letters 166, no. 2 (May 2001): 185–91. http://dx.doi.org/10.1016/s0304-3835(01)00428-1.
Full text
23
Saitoh, A., S. Shimada, and M. C. Udey. "184 Expression of wnt genes in murine epidermis." Journal of Dermatological Science 15, no. 2 (August 1997): 133. http://dx.doi.org/10.1016/s0923-1811(97)81887-7.
Full text
24
Labus, Marie B., Christina M. Stirk, W. Douglas Thompson, and William T. Melvin. "Expression of Wnt genes in early wound healing." Wound Repair and Regeneration 6, no. 1 (January 1998): 58–64. http://dx.doi.org/10.1046/j.1524-475x.1998.60109.x.
Full text
25
Masliah-Planchon, Julien, Emmanuelle Lechapt-Zalcman, Jean-Baptiste Aillaud, Olivier Ayrault, Célio Pouponnot, Francois Doz, Olivier Delattre, and Franck Bourdeaut. "MBRS-37. RECURRENT ACTIVATING MUTATIONS OF AKT GENES IN WNT-ACTIVATED MEDULLOBLASTOMAS." Neuro-Oncology 22, Supplement_3 (December 1, 2020): iii404. http://dx.doi.org/10.1093/neuonc/noaa222.548.
Full textAbstract:
Abstract Medulloblastoma (MB) can be classified into four distinct molecular subgroups (WNT group, SHH group, group 3, and group 4). Medulloblastoma of the WNT subgroup (WNT-MB) are commonly associated with favorable prognosis. Prospective molecular analysis based on a combination of CGH-array, targeted NGS and Nanostring-based subgrouping on 272 MB was conducted. Our custom targeted NGS panel of 75 genes includes genes recurrently affected in MB together with actionable genes with therapeutic purpose including some involved in the PIK3/AKT signaling pathway. Among the 272 MB analyzed, 26 cases (9.6%) belonged to the WNT subgroup based on CTNNB1 mutations, monosomy of chromosome 6 and Nanostring-based molecular subgrouping. Our targeted NGS revealed three hotspot activating mutations in AKT3 in WNT-MB and only one cases in another MB subgroup (in a group 4 MB; among the 33 cases of confirmed group 4 MB in our cohort). We subsequently performed Sanger sequencing of the hotspot Glu17 codon of AKT1, AKT2, and AKT3 in 42 additional WNT-MB. This analysis revealed six additional activating mutations of AKT genes (four AKT3 and two AKT1 hotspots mutations) in WNT-MB. Altogether, we report 9/68 (13.2%) cases of WNT-MB with AKT genes mutations (two mutations in AKT1 and seven mutations in AKT3). Our molecular analysis revealed AKT hotspot mutations that presumably activate the PIK3/AKT signaling pathway in WNT-MB. Even though WNT-MB is the subgroup of MB with the most favorable prognosis, this result emphasizes a possibility of targeted therapy that need to be further explored in vitro and in vivo.
26
Kim, Soyoung, Gahyeon Song, Taebok Lee, Minseong Kim, Jeongrae Kim, Hyeryun Kwon, Jiyoung Kim, et al. "PARsylated transcription factor EB (TFEB) regulates the expression of a subset of Wnt target genes by forming a complex with β-catenin-TCF/LEF1." Cell Death & Differentiation 28, no. 9 (March 22, 2021): 2555–70. http://dx.doi.org/10.1038/s41418-021-00770-7.
Full textAbstract:
AbstractWnt signaling is mainly transduced by β-catenin via regulation of the β-catenin destruction complex containing Axin, APC, and GSK3β. Transcription factor EB (TFEB) is a well-known master regulator of autophagy and lysosomal biogenesis processes. TFEB’s nuclear localization and transcriptional activity are also regulated by various upstream signals. In this study, we found that Wnt signaling induces the nuclear localization of TFEB and the expression of Wnt target genes is regulated by TFEB-β-catenin-TCF/LEF1 as well as β-catenin-TCF/LEF1 complexes. Our biochemical data revealed that TFEB is a part of the β-catenin destruction complex, and destabilization of the destruction complex by knockdown of either Axin or APC causes nuclear localization of TFEB. Interestingly, RNA-sequencing analysis revealed that about 27% of Wnt3a-induced genes were TFEB dependent. However, these “TFEB mediated Wnt target genes” were different from TFEB target genes involved in autophagy and lysosomal biogenesis processes. Mechanistically, we found that Tankyrase (TNKS) PARsylates TFEB with Wnt ON signaling, and the nuclear localized PARsylated TFEB forms a complex with β-catenin-TCF/LEF1 to induce the “TFEB mediated Wnt target genes”. Finally, we found that in various types of cancer, the levels of TFEB mediated Wnt target genes exhibit strong correlations with the level of Axin2, which represents the activity of Wnt signaling. Overall, our data suggest that Wnt signaling induces the expression of a subset of genes that are distinct from previously known genes regulated by the β-catenin-TCF/LEF1 complex or TFEB, by forming a transcription factor complex consisting of PARsylated TFEB and β-catenin-TCF/LEF1.
27
Rhen, Turk, Zachary Even, Alaina Brenner, Alexandra Lodewyk, Debojyoti Das, Sunil Singh, and Rebecca Simmons. "Evolutionary Turnover in Wnt Gene Expression but Conservation of Wnt Signaling during Ovary Determination in a TSD Reptile." Sexual Development 15, no. 1-3 (2021): 47–68. http://dx.doi.org/10.1159/000516973.
Full textAbstract:
Temperature-dependent sex determination (TSD) is a well-known characteristic of many reptilian species. However, the molecular processes linking ambient temperature to determination of gonad fate remain hazy. Here, we test the hypothesis that Wnt expression and signaling differ between female- and male-producing temperatures in the snapping turtle <i>Chelydra serpentina</i>. Canonical Wnt signaling involves secretion of glycoproteins called WNTs, which bind to and activate membrane bound receptors that trigger β-catenin stabilization and translocation to the nucleus where β-catenin interacts with TCF/LEF transcription factors to regulate expression of Wnt targets. Non-canonical Wnt signaling occurs via 2 pathways that are independent of β-catenin: one involves intracellular calcium release (the Wnt/Ca<sup>2+</sup> pathway), while the other involves activation of RAC1, JNK, and RHOA (the Wnt/planar cell polarity pathway). We screened 20 Wnt genes for differential expression between female- and male-producing temperatures during sex determination in the snapping turtle. Exposure of embryos to the female-producing temperature decreased expression of 7 Wnt genes but increased expression of 2 Wnt genes and <i>Rspo1</i> relative to embryos at the male-producing temperature. Temperature also regulated expression of putative Wnt target genes in vivo and a canonical Wnt reporter (6x TCF/LEF sites drive H2B-GFP expression) in embryonic gonadal cells in vitro. Results indicate that Wnt signaling was higher at the female- than at the male-producing temperature. Evolutionary analyses of all 20 Wnt genes revealed that thermosensitive Wnts, as opposed to insensitive Wnts, were less likely to show evidence of positive selection and experienced stronger purifying selection within TSD species.
28
Heijink, Irene H., Harold G. de Bruin, Robin Dennebos, Marnix R. Jonker, Jacobien A. Noordhoek, Corry-Anke Brandsma, Maarten van den Berge, and Dirkje S. Postma. "Cigarette smoke-induced epithelial expression of WNT-5B: implications for COPD." European Respiratory Journal 48, no. 2 (April 28, 2016): 504–15. http://dx.doi.org/10.1183/13993003.01541-2015.
Full textAbstract:
Wingless/integrase-1 (WNT) signalling is associated with lung inflammation and repair, but its role in chronic obstructive pulmonary disease (COPD) pathogenesis is unclear. We investigated whether cigarette smoke-induced dysregulation of WNT-5B contributes to airway remodelling in COPD.We analysed WNT-5B protein expression in the lung tissue of COPD patients and (non)smoking controls, and investigated the effects of cigarette smoke exposure on WNT-5B expression in COPD and control-derived primary bronchial epithelial cells (PBECs). Additionally, we studied downstream effects of WNT-5B on remodelling related genes fibronectin, matrix metalloproteinase (MMP)-2, MMP-9 and SnaiI in BEAS-2B and air–liquid interface (ALI)-cultured PBECs.We observed that airway epithelial WNT-5B expression is significantly higher in lung tissue from COPD patients than controls. Cigarette smoke extract significantly increased mRNA expression of WNT-5B in COPD, but not control-derived PBECs. Exogenously added WNT-5B augmented the expression of remodelling related genes in BEAS-2B cells, which was mediated by transforming growth factor (TGF)-β/Smad3 signalling. In addition, WNT-5B upregulated the expression of these genes in ALI-cultured PBECs, particularly PBECs from COPD patients.Together, our results provide evidence that exaggerated WNT-5B expression upon cigarette smoke exposure in the bronchial epithelium of COPD patients leads to TGF-β/Smad3-dependent expression of genes related to airway remodelling.
29
Salinas, P. C., C. Fletcher, N. G. Copeland, N. A. Jenkins, and R. Nusse. "Maintenance of Wnt-3 expression in Purkinje cells of the mouse cerebellum depends on interactions with granule cells." Development 120, no. 5 (May 1, 1994): 1277–86. http://dx.doi.org/10.1242/dev.120.5.1277.
Full textAbstract:
Wnt genes encode secreted proteins implicated in cell fate changes during development. To define specific cell populations in which Wnt genes act, we have examined Wnt expression in the cerebellum. This part of the brain has a relatively simple structure and contains well-characterized cell populations. We found that Wnt-3 is expressed during development of the cerebellum and that expression is restricted to the Purkinje cell layer in the adult. Wnt-3 expression in Purkinje cells increases postnatally as granule cells start to make contacts with Purkinje cells. To investigate whether interactions with granule cells influence Wnt-3 expression in Purkinje cells, we examined gene expression in several mouse mutants, using the expression of En-2 to follow the fate of granule cells. In the weaver mutant, in which granule cells fail to migrate and subsequently die in the external granular layer, Wnt-3 expression was normal at postnatal day 15 (P15). At that time, some granule cells are still present in the external granular layer. At P28, however, when granule cells could no longer be detected, Wnt-3 expression was almost absent. In the meander tail mutant, in which the anterior cerebellar lobes lack granule cells, Wnt-3 expression was only detected in the normal posterior lobes. Since En genes are implicated in cell-cell interactions mediated by Wnt genes, we examined En-2/En-2 mutant mice, finding normal Wnt-3 expression, indicating that the effect of granule cells on the maintenance of Wnt-3 is not mediated by En-2. Our results show that Wnt-3 expression in Purkinje cells is modulated by their presynaptic granule cells at the time of neuronal maturation.
30
Ho, Li-Lun, Amit Sinha, Michael Verzi, Kathrin M. Bernt, Scott A. Armstrong, and Ramesh A. Shivdasani. "DOT1L-Mediated H3K79 Methylation in Chromatin Is Dispensable for Wnt Pathway-Specific and Other Intestinal Epithelial Functions." Molecular and Cellular Biology 33, no. 9 (February 19, 2013): 1735–45. http://dx.doi.org/10.1128/mcb.01463-12.
Full textAbstract:
Methylation of H3K79 is associated with chromatin at expressed genes, though it is unclear if this histone modification is required for transcription of all genes. Recent studies suggest that Wnt-responsive genes depend particularly on H3K79 methylation, which is catalyzed by the methyltransferase DOT1L. Human leukemias carrying MLL gene rearrangements show DOT1L-mediated H3K79 methylation and aberrant expression of leukemogenic genes. DOT1L inhibitors reverse these effects, but their clinical use is potentially limited by toxicity in Wnt-dependent tissues such as intestinal epithelium. Genome-wide positioning of the H3K79me2 mark in Lgr5 + mouse intestinal stem cells and mature intestinal villus epithelium correlated with expression levels of all transcripts and not with Wnt-responsive genes per se . Selective Dot1l disruption in Lgr5 + stem cells or in whole intestinal epithelium eliminated H3K79me2 from the respective compartments, allowing genetic evaluation of DOT1L requirements. The absence of methylated H3K79 did not impair health, intestinal homeostasis, or expression of Wnt target genes in crypt epithelium for up to 4 months, despite increased crypt cell apoptosis. Global transcript profiles in Dot1l -null cells were barely altered. Thus, H3K79 methylation is not essential for transcription of Wnt-responsive or other intestinal genes, and intestinal toxicity is not imperative when DOT1L is rendered inactive in vivo .
31
Isani, Mubina A., Kristin Gee, Kathy Schall, Christopher R. Schlieve, Alexa Fode, Kathryn L. Fowler, and Tracy C. Grikscheit. "Wnt signaling inhibition by monensin results in a period of Hippo pathway activation during intestinal adaptation in zebrafish." American Journal of Physiology-Gastrointestinal and Liver Physiology 316, no. 6 (June 1, 2019): G679—G691. http://dx.doi.org/10.1152/ajpgi.00343.2018.
Full textAbstract:
Intestinal adaptation (IA) is a critical response to increase epithelial surface area after intestinal loss. Short bowel syndrome (SBS) may follow massive intestinal resection in human patients, particularly without adequate IA. We previously validated a model in zebrafish (ZF) that recapitulates key SBS pathophysiological features. Previous RNA sequencing in this model identified upregulation of genes in the Wnt and Hippo pathways. We therefore sought to identify the timeline of increasing cell proliferation and considered the signaling that might underpin the epithelial remodeling of IA in SBS. SBS was created in a ZF model as previously reported and compared with sham fish with and without exposure to monensin, an ionophore known to inhibit canonical Wnt signaling. Rescue of the monensin effects was attempted with a glycogen synthase kinase 3 inhibitor that activates wnt signaling, CHIR-99021. A timeline was constructed to identify peak cellular proliferation, and the Wnt and Hippo pathways were evaluated. Peak stem cell proliferation and morphological changes of adaptation were identified at 7 days. Wnt inhibition diminished IA at 2 wk and resulted in activation of genes of the Wnt/β-catenin and Yes-associated protein (YAP)/Hippo pathway. Increased cytoplasmic YAP was observed in monensin-treated SBS fish. Genes of the WASP-interacting protein (WIP) pathway were elevated during Wnt blockade. In conclusion, cellular proliferation and morphological changes accompany SBS even in attempted Wnt blockade. Wnt/β-catenin, YAP/Hippo pathway, and WIP pathway genes increase during early Wnt blockade. Further understanding of the effects of Wnt and YAP pathway signaling in proliferating stem cells might enrich our knowledge of targets to assist IA. NEW & NOTEWORTHY Intestinal adaptation is a critical response to increase epithelial surface area after large intestinal losses. Inhibition of Wnt/β-catenin signaling impairs intestinal adaptation in a zebrafish model of short bowel syndrome. There is a subsequent upregulation in genes of the Yes-associated protein/Hippo and WIP pathway. These may be targets for future human therapies, as patients are salvaged by the compensation of increased intestinal epithelial surface area through successful intestinal adaptation.
32
Ziegler, Slava, Sonja Röhrs, Lara Tickenbrock, Tarik Möröy, Ludger Klein-Hitpass, Ingrid R. Vetter, and Oliver Müller. "Novel target genes of the Wnt pathway and statistical insights into Wnt target promoter regulation." FEBS Journal 272, no. 7 (March 9, 2005): 1600–1615. http://dx.doi.org/10.1111/j.1742-4658.2005.04581.x.
Full text
33
Caracci, Mario O., Miguel E. Ávila, and Giancarlo V. De Ferrari. "Synaptic Wnt/GSK3βSignaling Hub in Autism." Neural Plasticity 2016 (2016): 1–10. http://dx.doi.org/10.1155/2016/9603751.
Full textAbstract:
Hundreds of genes have been associated with autism spectrum disorders (ASDs) and the interaction of weak andde novovariants derive from distinct autistic phenotypes thus making up the “spectrum.” The convergence of these variants in networks of genes associated with synaptic function warrants the study of cell signaling pathways involved in the regulation of the synapse. The Wnt/β-catenin signaling pathway plays a central role in the development and regulation of the central nervous system and several genes belonging to the cascade have been genetically associated with ASDs. In the present paper, we review basic information regarding the role of Wnt/β-catenin signaling in excitatory/inhibitory balance (E/I balance) through the regulation of pre- and postsynaptic compartments. Furthermore, we integrate information supporting the role of the glycogen synthase kinase 3β(GSK3β) in the onset/development of ASDs through direct modulation of Wnt/β-catenin signaling. Finally, given GSK3βactivity as key modulator of synaptic plasticity, we explore the potential of this kinase as a therapeutic target for ASD.
34
CHTARBOVA, Slava, Inko NIMMRICH, Silke ERDMANN, Peter HERTER, Matthias RENNER, Jan KITAJEWSKI, and Oliver MÜLLER. "Murine Nr4a1 and Herpud1 are up-regulated by Wnt-1, but the homologous human genes are independent from β-catenin activation." Biochemical Journal 367, no. 3 (November 1, 2002): 723–28. http://dx.doi.org/10.1042/bj20020699.
Full textAbstract:
The Wnt signal transduction pathway regulates morphogenesis and mitogenesis of cells in multicellular organisms. A major downstream consequence of Wnt-1 signalling is the activation of β-catenin/T-cell factor (TCF)-mediated transcription. We compared Wnt-1-transformed murine mammary epithelial cells with control cells by subtractive hybridization. We found the two genes Nr4a1 and Herpud1 to be overexpressed in Wnt-1-transformed cells. Remarkably, the transcription levels of the two homologous human genes NR4A1 and HERPUD1 are neither activated in cells with activated β-catenin/TCF-mediated transcription nor can be induced by β-catenin transfection. These results indicate different regulation mechanisms of the two genes in murine and human cells.
35
Cheng, Xiping, Sun Y. Kim, Haruka Okamoto, Yurong Xin, George D. Yancopoulos, Andrew J. Murphy, and Jesper Gromada. "Glucagon contributes to liver zonation." Proceedings of the National Academy of Sciences 115, no. 17 (March 19, 2018): E4111—E4119. http://dx.doi.org/10.1073/pnas.1721403115.
Full textAbstract:
Liver zonation characterizes the separation of metabolic pathways along the lobules and is required for optimal function. Wnt/β-catenin signaling controls metabolic zonation by activating genes in the perivenous hepatocytes, while suppressing genes in the periportal counterparts. We now demonstrate that glucagon opposes the actions of Wnt/β-catenin signaling on gene expression and metabolic zonation pattern. The effects were more pronounced in the periportal hepatocytes where 28% of all genes were activated by glucagon and inhibited by Wnt/β-catenin. The glucagon and Wnt/β-catenin receptors and their signaling pathways are uniformly distributed in periportal and perivenous hepatocytes and the expression is not regulated by the opposing signal. Collectively, our results show that glucagon controls gene expression and metabolic zonation in the liver through a counterplay with the Wnt/β-catenin signaling pathway.
36
Halene, Stephanie, Ee-chun Cheng, Vincent Schulz, David Tuck, and Diane Krause. "OTT-MKL1 and MKL1 Inhibit Wnt Signaling." Blood 112, no. 11 (November 16, 2008): 2250. http://dx.doi.org/10.1182/blood.v112.11.2250.2250.
Full textAbstract:
Abstract The OTT-MKL1 fusion gene product is generated as a result of t(1;22) in a subset of acute megakaryoblastic leukemia predominantly encountered in young children. Due to myelofibrosis and the age at presentation, patient samples are scarce. We generated Human Erythroid Leukemia (HEL) cell derived cell lines with tet-inducible OTT, MKL1 and OTT-MKL1 to further elucidate the function of the respective proteins. HEL cells can be induced to differentiate down the megakaryocyte lineage by TPA. Induction with doxycycline resulted in transcription and translation of the respective genes within hours. While overexpression of MKL1 led to enhancement of megakaryocytic differentiation, both OTT and OTT-MKL1 overexpression led to cell death over the course of several days by apoptosis as evident by staining for Annexin V and morphology. The apoptotic cell death was greatly enhanced by concomitant induction of differentiation by TPA. We performed microarray analysis comparing uninduced and 8-hour tet-induced samples in the presence or absence of TPA. While overexpression of OTT had only a minimal effect on the transcriptome of the HEL cells, both MKL1 and OTT-MKL1 significantly affected the gene expression of many genes. Using a false discovery rate cut-off of p < 0.05, and assessing only those genes whose expression changed by greater than 2-fold, OTT-MKL1 and MKL1 induced the upregulation of 157 and 168 genes, respectively, and the downregulation of 56 and 62 genes, respectively. Only 20 genes were upregulated by both OTT-MKL1 and MKL1, and 12 genes were downregulated greater than 2-fold by both OTT-MKL1 and MKL1. GeneGo analysis comparing OTT-MKL1 over-expressing versus non-expressing cells revealed over-representation of the Wnt pathway. Among the differentially expressed genes implicated in the Wnt pathway were Frat1 and Frat2, which have been shown to inhibit GSK3β and lead to β-catenin nuclear accumulation, and thus stimulation of the Wnt pathway. At the same time, inhibitory NLK was upregulated and several down-stream targets of the Wnt pathway were downregulated. Spenito, the homolog of OTT in Drosophila, is known to have promoter-specific activating and inhibiting effects on Wnt target genes. We thus performed reporter assays to study the effects of OTT, MKL1 and OTT-MKL1 on the Wnt pathway. Using the TOP-/FOP-FLASH reporter system in 293T cells, there was a dose-dependent inhibition of β-catenin-mediated activation of the Tcf/Lef binding site promoter by MKL1 and OTT-MKL1. Full length OTT showed a minimal stimulatory effect only at low doses., while N-terminal OTT, lacking the SPOC domain and a dominant negative form of MKL1 lacking the transactivation domain each enhanced β-catenin induced Tcf/Lef mediated transcriptional activation. Studies to define the domains of OTT and MKL1 and the underlying mechanisms in hematopoietic cells are underway. These results suggest that MKL1 and OTT-MKL1 inhibit canonical Wnt signaling by inhibiting β-catenin induced transcription.
37
Lickert, Heiko, Andreas Kispert, Stefanie Kutsch, and Rolf Kemler. "Expression patterns of Wnt genes in mouse gut development." Mechanisms of Development 105, no. 1-2 (July 2001): 181–84. http://dx.doi.org/10.1016/s0925-4773(01)00390-2.
Full text
38
Sarkar, Lena, and Paul T. Sharpe. "Expression of Wnt signalling pathway genes during tooth development." Mechanisms of Development 85, no. 1-2 (July 1999): 197–200. http://dx.doi.org/10.1016/s0925-4773(99)00095-7.
Full text
39
Wang, Zhenkai, Yaqing Ye, Dan Liu, Xiaoqian Yang, and Fangyu Wang. "Hypermethylation of multiple Wnt antagonist genes in gastric neoplasia." Medicine 97, no. 52 (December 2018): e13734. http://dx.doi.org/10.1097/md.0000000000013734.
Full text
40
Murat, Sophie, Corinna Hopfen, and Alistair P. McGregor. "The function and evolution of Wnt genes in arthropods." Arthropod Structure & Development 39, no. 6 (November 2010): 446–52. http://dx.doi.org/10.1016/j.asd.2010.05.007.
Full text
41
Joyner, Alexandra L. "Engrailed, Wnt and Pax genes regulate midbrain-hindbrain development." Trends in Genetics 12, no. 1 (January 1996): 15–20. http://dx.doi.org/10.1016/0168-9525(96)81383-7.
Full text
42
Liu, Jun, Fei Xu, Peng Ji, Li Li, and Guofan Zhang. "Involvement of clustered oyster Wnt genes in gut formation." Journal of Oceanology and Limnology 36, no. 5 (September 2018): 1746–52. http://dx.doi.org/10.1007/s00343-018-7138-1.
Full text
43
Tribulo, Paula, James I. Moss, Manabu Ozawa, Zongliang Jiang, Xiuchun (Cindy) Tian, and Peter J. Hansen. "WNT regulation of embryonic development likely involves pathways independent of nuclear CTNNB1." Reproduction 153, no. 4 (April 2017): 405–19. http://dx.doi.org/10.1530/rep-16-0610.
Full textAbstract:
The bovine was used to examine the potential for WNT signaling to affect the preimplantation embryo. Expression of seven key genes involved in canonical WNT signaling declined to a nadir at the morula or blastocyst stage. Expression of 80 genes associated with WNT signaling in the morula and inner cell mass (ICM) and trophectoderm (TE) of the blastocyst was also evaluated. Many genes associated with WNT signaling were characterized by low transcript abundance. Seven genes were different between ICM and TE, and all of them were overexpressed in TE as compared to ICM, including WNT6, FZD1, FZD7, LRP6, PORCN, APC and SFRP1. Immunoreactive CTNNB1 was localized primarily to the plasma membrane at all stages examined from the 2-cell to blastocyst stages of development. Strikingly, neither CTNNB1 nor non-phospho (i.e., active) CTNNB1 was observed in the nucleus of blastomeres at any stage of development even after the addition of WNT activators to culture. In contrast, CTNNB1 associated with the plasma membrane was increased by activators of WNT signaling. The planar cell polarity pathway (PCP) could be activated in the embryo as indicated by an experiment demonstrating an increase in phospho-JNK in the nucleus of blastocysts treated with the non-canonical WNT11. Furthermore, WNT11 improved development to the blastocyst stage. In conclusion, canonical WNT signaling is attenuated in the preimplantation bovine embryo but WNT can activate the PCP component JNK. Thus, regulation of embryonic development by WNT is likely to involve activation of pathways independent of nuclear actions of CTNNB1.
44
Adjei-Fremah, Sarah, Emmanuel Kwaku Asiamah, Kingsley Ekwemalor, Louis Jackai, Keith Schimmel, and Mulumebet Worku. "Modulation of Bovine Wnt Signaling Pathway Genes by Cowpea Phenolic Extract." Journal of Agricultural Science 8, no. 3 (February 16, 2016): 21. http://dx.doi.org/10.5539/jas.v8n3p21.
Full textAbstract:
<p class="ANMmaintext">The Wingless (Wnt) signaling pathway is a conserved pathway with essential roles in cellular and biological processes in mammals. Wnt signal transduction has been implicated in inflammation, innate immunity and homeostasis via Toll-like receptor and NF-kB pathways. Plant bioactive compounds are capable of modulating the Wnt signalling pathway, which can be either a canonical (B-Catenin dependent) or non-canonical (B-Catenin independent) mechanism. This study evaluated the effect of cowpea phenolic extract (CPE) on the expression and modulation of genes of the Wnt signaling pathway in cow blood. Whole blood collected from six Holstein-Friesian cows was treated with 10 ug/ml of the extract, and evaluated for packed cell volume (PCV), total count and viability of cells, and white blood cell differential count before and after treatment. Cowpea phenolic extract agonist activity in blood was measured using a Bovine toll-like receptor (TLR) 2, and TLR 4 ELISA kit. Total RNA was isolated from the blood cell pellet, reverse transcribed and used for real-time PCR to detect expression of 84 genes on the Cow Wnt signaling pathway array. The total cell-associated B-Catenin level was measured using a commercial ELISA kit. There was no treatment effect on PCV, total cell and viability (P > 0.05). The percentage of mononuclear cells were influenced by treatment, % monocytes (P = 0.0136) decreased and % lymphocytes (P = 0.0114) increased. Treatment with CPE activated cow blood cells, increased TLR2 release and total B-Catenin levels (6 ng/ml, P < 0.05), but TLR4 was not detected. Polyphenols from cowpea modulated the expression of Wnt signalling genes, especially canonical B-Catenin mediated pathway genes. Modulation of Wingless gene expression may be an important mechanism by which polyphenols in cowpea feed impact cellular immune response and homeostasis. Thus, further studies are needed to determine the association of CPE-mediated Wnt gene modulation on blood leucocytes subpopulations and animal health.</p>
45
Zhang, Han, Suping Zhang, Emanuela M. Ghia, Michael Y. Choi, Jieyu Zhang, Liguang Chen, George F. Widhopf II, Laura Z. Rassenti, and Thomas J. Kipps. "Cirmtuzumab Inhibits Non-Canonical Wnt Signaling without Enhancing Canonical Wnt/β-Catenin Signaling in Chronic Lymphocytic Leukemia." Blood 132, Supplement 1 (November 29, 2018): 2652. http://dx.doi.org/10.1182/blood-2018-99-119606.
Full textAbstract:
Abstract ROR1 is a receptor tyrosine kinase-like orphan receptor for Wnt5a that is expressed by cells during embryogenesis and by the neoplastic cells of a variety of cancers, including chronic lymphocytic leukemia (CLL). ROR1 can induce activation of β-catenin-independent non-canonical Wnt-signaling. Studies reveal a cross-talk between the non-canonical Wnt-signaling pathway and the β-catenin-dependent canonical Wnt-signaling pathway, which we previously found was also activated in CLL (Lu D, et al, PNAS 101:31118-3123, 2004). Prior studies indicated that silencing a related Wnt5a receptor, ROR2, could augment canonical Wnt-signaling induced by Wnt3a. In this study, we examined whether genetic silencing of ROR1 or inhibition of ROR1-signaling also could influence canonical Wnt signaling. To inhibit ROR1 signaling we used the humanized anti-ROR1 mAb cirmtuzumab, which is being evaluated in patients with CLL (Choi MY, et al, Cell Stem Cell, 22:951, 2018). Surprisingly, we found that CRISPR/Cas9 deletion of ROR1 in 293T cells also could enhance the capacity of Wnt3a to activate canonical Wnt-signaling, albeit to a lesser extent than CRISPR/Cas9 deletion of ROR2; conversely, re-introduction of ROR1 into ROR1-deleted 293T cells suppressed Wnt3a-induced activation of canonical Wnt-signaling. In contrast, treatment of wildtype 293T cells with cirmtuzumab did not enhance Wnt3a-induced activation of canonical Wnt-signaling, but nonetheless suppressed ROR1-dependent non-canonical signaling induced by Wnt5a. We examined the influence of ROR1 on canonical Wnt-signaling in CLL. First, we examined whether the relative expression of ROR1 influenced the relative levels of genes induced by activation of the canonical Wnt-signaling pathway. Gene set enrichment analysis (GSEA) of gene-expression data on CLL cells of different patients (n=448, GSE13204) revealed that CLL cells with low-level expression of ROR1 (ROR1Low) did not have increased levels of genes induced by activation of canonical Wnt-signaling relative to those noted in CLL cells with high-level expression of ROR1 (ROR1Hi). Nonetheless, ROR1Hi CLL cells did have increased levels of genes induced by activation of non-canonical Wnt signaling compared to ROR1Low CLL cells. As in 293T cells, siRNA-mediated knockdown of ROR1 in ROR1Hi CLL cells could enhance the capacity of Wnt3a to increase the levels of genes induced by canonical Wnt-signaling (e.g. MYC, CCND1). However, treatment of the same CLL cells with cirmtuzumab did not enhance the levels of such genes in response to Wnt3a, even at concentrations that exceeded those required to inhibit Wnt5a-induced ROR1-dependent non-canonical Wnt-signaling. We examined whether these findings also applied to CLL cells treated with cirmtuzumab in vivo. For this, we performed gene-set enrichment analyses on the transcriptomes of CLL cells collected from patients before and after treatment with cirmtuzumab in a recently completed phase I clinical trial (Choi MY, et al, Cell Stem Cell, 22:951, 2018). Although treatment with cirmtuzumab repressed expression of genes induced by activation of non-canonical Wnt signaling, we did not observe changes in the levels of genes induced by activation of the canonical Wnt signaling pathway. Collectively, this study demonstrates that cirmtuzumab can inhibit non-canonical Wnt signaling without enhancing canonical Wnt signaling in CLL, in contrast to what we observed in CLL cells silenced for ROR1. As such, treatment with cirmtuzumab may represent a more selective approach to suppressing non-canonical Wnt5a signaling than strategies aimed at genetic down-modulation or silencing of ROR1. Disclosures Choi: Rigel: Consultancy; Pharmacyclics: Consultancy, Research Funding, Speakers Bureau; Gilead: Speakers Bureau; AbbVie, Inc: Consultancy, Speakers Bureau; Genentech: Speakers Bureau.
46
Wöhrle, Simon, Britta Wallmen, and Andreas Hecht. "Differential Control of Wnt Target Genes Involves Epigenetic Mechanisms and Selective Promoter Occupancy by T-Cell Factors." Molecular and Cellular Biology 27, no. 23 (October 8, 2007): 8164–77. http://dx.doi.org/10.1128/mcb.00555-07.
Full textAbstract:
ABSTRACT Canonical Wnt signaling and its nuclear effectors, β-catenin and the family of T-cell factor (TCF) DNA-binding proteins, belong to the small number of regulatory systems which are repeatedly used for context-dependent control of distinct genetic programs. The apparent ability to elicit a large variety of transcriptional responses necessitates that β-catenin and TCFs distinguish precisely between genes to be activated and genes to remain silent in a specific context. How this is achieved is unclear. Here, we examined patterns of Wnt target gene activation and promoter occupancy by TCFs in different mouse cell culture models. Remarkably, within a given cell type only Wnt-responsive promoters are bound by specific subsets of TCFs, whereas nonresponsive Wnt target promoters remain unoccupied. Wnt-responsive, TCF-bound states correlate with DNA hypomethylation, histone H3 hyperacetylation, and H3K4 trimethylation. Inactive, nonresponsive promoter chromatin shows DNA hypermethylation, is devoid of active histone marks, and additionally can show repressive H3K27 trimethylation. Furthermore, chromatin structural states appear to be independent of Wnt pathway activity. Apparently, cell-type-specific regulation of Wnt target genes comprises multilayered control systems. These involve epigenetic modifications of promoter chromatin and differential promoter occupancy by functionally distinct TCF proteins, which together determine susceptibility to Wnt signaling.
47
Ziemer, Lisa Taneyhill, Diane Pennica, and Arnold J. Levine. "Identification of a Mouse Homolog of the Human BTEB2Transcription Factor as a β-Catenin-Independent Wnt-1-Responsive Gene." Molecular and Cellular Biology 21, no. 2 (January 15, 2001): 562–74. http://dx.doi.org/10.1128/mcb.21.2.562-574.2001.
Full textAbstract:
ABSTRACT The Wnt/Wg signaling pathway functions during development to regulate cell fate determination and patterning in various organisms. Two pathways are reported to lie downstream of Wnt signaling in vertebrates. The canonical pathway relies on the activation of target genes through the β-catenin–Lef/TCF complex, while the noncanonical pathway employs the activation of protein kinase C (PKC) and increases in intracellular calcium to induce target gene expression. cDNA subtractive hybridization between a cell line that overexpresses Wnt-1 (C57MG/Wnt-1) and the parental cell line (C57MG) was performed to identify downstream target genes of Wnt-1 signaling. Among the putative Wnt-1 target genes, we have identified a mouse homolog of the gene encoding human transcription factor basic transcription element binding protein 2 (mBTEB2). ThemBTEB2 transcript is found at high levels in mammary tissue taken from a transgenic mouse overexpressing Wnt-1 (both tissue prior to active proliferation and tumor tissue) but is barely detectable in wild-type mouse mammary glands. The regulation of mBTEB2 by Wnt-1 signaling in tissue culture occurs through a β-catenin–Lef/TCF-independent mechanism, as it is instead partially regulated by PKC. The Wnt-1-induced, PKC-dependent activation of mouse BTEB2 in C57MG cells, as well as the ability of Wnt-1 to stabilize β-catenin in these cells, is consistent with the hypothesis that both the noncanonical and canonical Wnt pathways are activated concomitantly in the same cell. These results suggest that mBTEB2 is a biologically relevant target of Wnt-1 signaling that is activated through a β-catenin-independent, PKC-sensitive pathway in response to Wnt-1.
48
Dharmarajan, A., N. Zeps, and S. McLaren. "003.Expression of secreted frizzled related protein-4 (sFRP-4) and associated Wnt signalling in cancer and apoptosis." Reproduction, Fertility and Development 17, no. 9 (2005): 63. http://dx.doi.org/10.1071/srb05abs003.
Full textAbstract:
We examined the interplay between Wnt and secreted frizzled related protein-4 (sFRP4) in estradiol induced cell growth in breast cancer cells (MCF-7), and also determined the in vivo distribution of sFRP-4 in human breast cancer. MCF-7 cells were treated with estradiol, sFRP-4 conditioned media and a combination of the two. Real-time RT-PCR and Western blot analysis were used to determine the expression of the sFRP-4 and its associated Wnt signalling molecules following treatment. Immunohistochemistry was performed to examine sFRP-4 expression patterns in human breast cancers. Estradiol treatment up-regulated the expression of the Wnt signalling genes Wnt-10b, beta-catenin and fz-4 (P < 0.001 for all genes). This up-regulation was not associated with an increase in the Wnt signalling pathway as measured by the levels of active beta-catenin. sFRP-4 conditioned media reduced MCF-7 cell proliferation, down-regulated the Wnt signalling genes beta-catenin and fz-4 as well as down-regulating wnt signalling activity. sFRP-4 was able to reduce the proliferation of estradiol stimulated MCF-7 cells. Cytoplasmic sFRP-4 protein was expressed in all breast tumours examined, with intense staining evident in the lobular carcinoma in situ and the ductal carcinoma. These data demonstrate that sFRP-4 is a potent inhibitor of the Wnt signalling pathway in MCF-7 cells, acting not only to down-regulate the activity of the wnt signalling pathway, but also down-regulate the transcription of Wnt signalling genes. The results of these in vitro and immunohistochemical experiments warrant further investigation as to whether sFRP-4 expression can be indicative of prognosis in human breast cancer. In addition to breast cancer, we have also examined the role of sFRP-4 in other cancers such as ovarian and prostate.
49
Griffiths, Elizabeth A., Craig M. Hooker, Michael A. McDevitt, Judith E. Karp, James G. Herman, and Hetty E. Carraway. "Acute Myeloid Leukemia Is Characterized by Wnt Pathway Inhibitor Promoter Methylation." Blood 112, no. 11 (November 16, 2008): 2253. http://dx.doi.org/10.1182/blood.v112.11.2253.2253.
Full textAbstract:
Abstract The Wnt pathway contributes to a stem-cell like phenotype in a variety of cancer subtypes. Nuclear localization of non-phosphorylated, active β-catenin is a surrogate marker for Wnt pathway activation and has been associated with adverse outcome in patients with acute myeloid leukemia (AML). Wnt pathway inhibitors including APC, DKK1, DKK3, LKB1/STK11, RASSF1A, RUNX3, SFRP1, SFRP2, SFRP4, SFRP5, SOX17, and WIF1 contain extensive promoter region CpG islands. Wnt pathway inhibitors are silenced by promoter methylation in many malignancies including lung cancer, colon cancer and acute lymphoid leukemias. To determine if methylation of these Wnt pathway inhibitors is present in AML, we evaluated leukemia cell lines (i.e., K562, HNT34, KG1, KG1A, U937, and HL60) for evidence of promoter methylation. Additionally, 188 AML patient (median age 61 years) samples from the Johns Hopkins Hospital leukemia tumor bank were assessed for the presence of Wnt pathway inhibitor methylation. All samples were bisulfite treated and evaluated for promoter methylation using methylation specific PCR. Diagnostic samples from a subgroup of patients with normal cytogenetics (n=73) who received high dose induction therapy were evaluated for potential associations between methylation of individual Wnt pathway inhibitor genes or total number of methylated genes and event free or overall survival. RESULTS: Extensive promoter methylation of the Wnt pathway inhibitor genes was observed in leukemia cell lines. Of the primary leukemia samples, 85% had at least one methylated gene. Promoter methylation of Wnt inhibitors was common in these samples with the following frequencies: DKK1 (16%;30/188), DKK3 (8%;15/188), RUNX3 (27%;50/188), SFRP1 (34%;63/188), SFRP2 (66%;124/188), SFRP4 (9%;16/188), SFRP5 (54%;102/188), SOX17 (29%;54/188), and WIF1 (32%;61/188). This is among the first comprehensive evaluations of Wnt pathway inhibitor methylation in primary samples from AML patients. The frequency of methylation seen here is comparable to that observed in established tumor suppressor genes in patients with AML, including p15INK4B, SOCS1 and CDH1. In marked contrast with epithelial tumors, methylation of APC (2%;2/108) and RASSF1A (0%;0/188) was rare. LKB1/STK11 methylation was also uncommon (2%;2/108). Previous reports have associated Wnt pathway activation with poor prognosis. In our treated patients with normal cytogenetics, no correlation was observed between methylation of Wnt pathway inhibitors and event free or overall survival. In conclusion, in patients with AML (a) there is a high frequency of Wnt pathway inhibitor methylation; (b) Wnt pathway inhibitor methylation is distinct from that observed in epithelial malignancies; and (c) methylation of Wnt pathway genes does not correlate with adverse clinical outcome.
50
Tapia-Rojas, Cheril, Andreas Schüller, Carolina B. Lindsay, Roxana C. Ureta, Cristóbal Mejías-Reyes, Juan Hancke, Francisco Melo, and Nibaldo C. Inestrosa. "Andrographolide activates the canonical Wnt signalling pathway by a mechanism that implicates the non-ATP competitive inhibition of GSK-3β: autoregulation of GSK-3β in vivo." Biochemical Journal 466, no. 2 (February 20, 2015): 415–30. http://dx.doi.org/10.1042/bj20140207.
Full textAbstract:
Andrographolide activates the canonical Wnt pathway and induces the transcription of Wnt target genes through a mechanism independent of Wnt ligand binding to its receptor, by direct substrate-competitive inhibition of GSK-3.