C. elegans POP-1/TCF functions in a canonical Wnt pathway that controls cell migration and in a noncanonical Wnt pathway that controls cell polarity

Development ◽  
2001 ◽  
Vol 128 (4) ◽  
pp. 581-590 ◽  
Author(s):  
M. Herman
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Polarity ◽  
Wnt Pathway ◽  
Beta Catenin ◽  
Wild Type ◽  
C Elegans ◽  
Cell Divisions ◽  
Canonical Wnt Pathway ◽  
Canonical Wnt

In Caenorhabditis elegans, Wnt signaling pathways are important in controlling cell polarity and cell migrations. In the embryo, a novel Wnt pathway functions through a (beta)-catenin homolog, WRM-1, to downregulate the levels of POP-1/Tcf in the posterior daughter of the EMS blastomere. The level of POP-1 is also lower in the posterior daughters of many anteroposterior asymmetric cell divisions during development. I have found that this is the case for of a pair of postembryonic blast cells in the tail. In wild-type animals, the level of POP-1 is lower in the posterior daughters of the two T cells, TL and TR. Furthermore, in lin-44/Wnt mutants, in which the polarities of the T cell divisions are frequently reversed, the level of POP-1 is frequently lower in the anterior daughters of the T cells. I have used a novel RNA-mediated interference technique to interfere specifically with pop-1 zygotic function and have determined that pop-1 is required for wild-type T cell polarity. Surprisingly, none of the three C. elegans (beta)-catenin homologs appeared to function with POP-1 to control T cell polarity. Wnt signaling by EGL-20/Wnt controls the migration of the descendants of the QL neuroblast by regulating the expression the Hox gene mab-5. Interfering with pop-1 zygotic function caused defects in the migration of the QL descendants that mimicked the defects in egl-20/Wnt mutants and blocked the expression of mab-5. This suggests that POP-1 functions in the canonical Wnt pathway to control QL descendant migration and in novel Wnt pathways to control EMS and T cell polarities.

Noncanonical Wnt5a Is Induced by HTLV-1 bZIP Factor, and Supports Proliferation and Migration of Adult T-Cell Leukemia Cell.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2405-2405
Author(s):  
Jun-ichirou Yasunaga ◽  
Guangyong Ma ◽  
Jun Fan ◽  
Masao Matsuoka
Keyword(s):  
T Cell ◽  
Wnt Signaling ◽  
Wnt Pathway ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia ◽  
Canonical Wnt Pathway ◽  
Bzip Factor ◽  
And Migration ◽  
Canonical Wnt

Abstract Abstract 2405 Adult T-cell leukemia (ATL) is a fatal malignancy of CD4-positive T-cells caused by human T-cell leukemia virus type1 (HTLV-1). HTLV-1 bZIP factor (HBZ) is encoded in the minus strand of HTLV-1 provirus, and is consistently expressed in HTLV-1-infected cells. It has been shown that HBZ promotes proliferation of T-cells, and HBZ-expressing transgenic mice develop T-cell lymphomas and systemic inflammations, suggesting that HBZ has the critical roles in pathogenesis of HTLV-1. However, the molecular mechanisms of HBZ-induced oncogenesis have not been clarified yet. The Wnt signaling is a highly conserved cellular signaling pathway in eukaryotes and the Wnt ligands have been found to trigger multiple pathways of Wnt signaling. The most well-studied cascade is the Wnt/β-catenin pathway (also known as the canonical Wnt pathway), which is β-catenin-dependent and mainly controls cell differentiation, proliferation, and apoptosis. Aberrant activation of the canonical Wnt pathway has been linked to many cancers. In contrast, it is known that the noncanonical Wnt pathway antagonizes the canonical pathway, while a representative noncanonical Wnt ligand, Wnt5a, is suggested to have both oncogenic and tumor suppressive properties in several malignancies. The significance of those Wnt pathways in HTLV-1-associated oncogenesis is still obscure. In this study, we found that HBZ markedly suppressed the canonical Wnt/β-catenin pathway. As a mechanism of HBZ-mediated Wnt suppression, we found that HBZ targets LEF1 and TCF1, the key transcription factors of the pathway, and impairs its DNA-binding ability. In contrast, HTLV-1 Tax protein interacted with Dvl and DAPLE, which are the regulators of the canonical Wnt signaling, and activated the pathway. Indeed, the canonical Wnt activation is not observed in ATL cells, and enforced activation of β-catenin in ATL cells inhibited cellular proliferation, implying that activation of the canonical Wnt pathway might have suppressive effect on ATL cells. On the other hand, HBZ induces the transcription of the noncanonical Wnt5a by enhancing its promoter activity. In addition, Wnt5a transcription level in ATL cells is significantly higher than in HTLV-1-uninifected control cells. Knockdown of Wnt5a impairs both proliferation and migration of ATL cells, suggesting that HBZ-induced Wnt5a supports development and progression of ATL. Our results implicate novel roles of HBZ in ATL leukemogenesis through dysregulation of both the canonical and noncanonical Wnt pathways. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Canonical Wnt signaling regulates branching morphogenesis of submandibular gland by modulating levels of lama5

2021 ◽  
Vol 52 ◽  
Author(s):  
Liming Gou ◽  
Xiaochun Ren ◽  
Ping Ji
Keyword(s):  
Organ Culture ◽  
Signaling Pathway ◽  
Branching Process ◽  
Wnt Pathway ◽  
Branching Morphogenesis ◽  
Beta Catenin ◽  
Fgf Signaling ◽  
Canonical Wnt Pathway ◽  
Culture Model ◽  
Canonical Wnt

Background: Branching morphogenesis is a crucial developmental mechanism for the formation of a typical bush-like structure of the submandibular gland (SMG). However, the detailed mechanism underlying this process remains to be fully understood. Here, we investigate whether a cross-talking may exist between Wnt/beta-catenin signaling pathway and lama5 during the branching process in SMG development. Methods: Embryonic mouse SMG organ culture model was established, and the validity of this model was confirmed. The roles of Wnt/beta-catenin signaling pathway, FGF signaling, and Lama5 in the branching process were investigated by morphogenesis assays. And the interactions between these signaling were also investigated and demonstrated by morphogenesis assays and gene expression patterns. Results: We demonstrated that E12 or E13 SMG organ culture model can be used as an ideal approach to study the process of branching morphogenesis. And branching morphogenesis assay revealed that the epithelial branching process would be promoted when the canonical Wnt pathway was inhibited and be significantly suppressed when wnt pathway is over activated. Further experiments indicated that FGF signaling acts most likely acts upstream as a negative regulator of the canonical Wnt pathway during the branching process, whose effect could be partially reversed by Wnt3a. And we further demonstrated that Wnt/beta-catenin signaling regulates the branching morphogenesis through Lama5. Conclusion: Our present work demonstrated that Wnt/beta-catenin signaling pathway acting downstream of FGF signaling may serve as a negative regulatory mechanism in the process of SMG branching morphogenesis through Lama5.

EGL-27 is similar to a metastasis-associated factor and controls cell polarity and cell migration in C. elegans

Development ◽  
1999 ◽  
Vol 126 (5) ◽  
pp. 1055-1064 ◽  
Author(s):  
M.A. Herman ◽  
Q. Ch'ng ◽  
S.M. Hettenbach ◽  
T.M. Ratliff ◽  
C. Kenyon ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Division ◽  
T Cell ◽  
Cell Polarity ◽  
Wnt Pathway ◽  
Hox Gene ◽  
C Elegans ◽  
Metastatic Cells ◽  
Mosaic Analysis ◽  
Wnt Pathways

Mutations in the C. elegans gene egl-27 cause defects in cell polarity and cell migration: the polarity of the asymmetric T cell division is disrupted and the descendants of the migratory QL neuroblast migrate incorrectly because they fail to express the Hox gene mab-5. Both of these processes are known to be controlled by Wnt pathways. Mosaic analysis indicates that egl-27 function is required in the T cell for proper cell polarity. We cloned egl-27 and discovered that a domain of the predicted EGL-27 protein has similarity to Mta1, a mammalian factor overexpressed in metastatic cells. Overlaps in the phenotypes of egl-27 and Wnt pathway mutants suggest that the EGL-27 protein interacts with Wnt signaling pathways in C. elegans.

Disruption of the Non-Canonical WNT Pathway in Lung Squamous Cell Carcinoma

2008 ◽  
Vol 2 ◽  
pp. CMO.S612 ◽  
Author(s):  
Eric H.L. Lee ◽  
Raj Chari ◽  
Andy Lam ◽  
Raymond T. Ng ◽  
John Yee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Wnt Pathway ◽  
Lung Squamous Cell Carcinoma ◽  
Beta Catenin ◽  
Related Protein ◽  
Canonical Wnt Pathway ◽  
Canonical Wnt

Disruptions of beta-catenin and the canonical Wnt pathway are well documented in cancer. However, little is known of the non-canonical branch of the Wnt pathway. In this study, we investigate the transcript level patterns of genes in the Wnt pathway in squamous cell lung cancer using reverse-transcriptase (RT)-PCR. It was found that over half of the samples examined exhibited dysregulated gene expression of multiple components of the non-canonical branch of the WNT pathway. In the cases where beta catenin ( CTNNB1) was not over-expressed, we identified strong relationships of expression between wingless-type MMTV integration site family member 5A ( WNT5A)/ frizzled homolog 2 ( FZD2), frizzled homolog 3 ( FZD3)/ dishevelled 2 ( DVL2), and low density lipoprotein receptor-related protein 5 ( LRP5)/ secreted frizzled-related protein 4 ( SFRP4). This is one of the first studies to demonstrate expression of genes in the non-canonical pathway in normal lung tissue and its disruption in lung squamous cell carcinoma. These findings suggest that the non-canonical pathway may have a more prominent role in lung cancer than previously reported.

scholarly journals Leptin regulates glucose homeostasis via the canonical WNT pathway

2021 ◽  
Author(s):  
Kaj Kamstra ◽  
Mohammed Z. Rizwan ◽  
Julia A. Horsfield ◽  
Dominik Pretz ◽  
Peter R. Shepherd ◽  
...  
Keyword(s):  
Body Weight ◽  
Glucose Homeostasis ◽  
Wnt Pathway ◽  
Wnt Signalling ◽  
Beta Catenin ◽  
Mediobasal Hypothalamus ◽  
Adult Mice ◽  
Conditional Deletion ◽  
Canonical Wnt Pathway ◽  
Canonical Wnt

SummaryLeptin is a body weight regulatory hormone, but it is arguably even more potent at regulating blood glucose levels. To further our understanding of the molecular mechanisms by which leptin controls glucose homeostasis, we have used transgenic zebrafish models and conditional deletion of beta catenin in the mediobasal hypothalamus of adult mice to show that Wnt signalling in the brain mediates glucoregulatory effects of leptin. In zebrafish, under normal feeding conditions, leptin regulates glucose homeostasis but not adipostasis. In times of nutrient excess, we found that leptin also regulates body weight and size in this species. Using a Wnt signalling reporter fish, we show that leptin directly activates the canonical Wnt pathway in vivo. Pharmacological inhibition of this pathway prevented the leptin-induced improvement in glucose tolerance. In adult mice, conditional deletion of the key Wnt effector molecule, β-catenin, in the mediobasal hypothalamus of male mice confirmed the essential role of the Wnt pathway in mediating leptin action and the neuroendocrine regulation of glucose homeostasis. Adult-onset β-catenin deletion in the mediobasal hypothalamus led to glucose intolerance, exacerbation of caloric intake and body weight gain under high fat diet, as well as resistance to exogenous leptin.

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