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

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.

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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 ◽

10.1242/dev.128.4.581 ◽

2001 ◽

Vol 128 (4) ◽

pp. 581-590 ◽

Cited By ~ 1

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.

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The Meckel-Gruber syndrome protein TMEM67 controls basal body positioning and epithelial branching morphogenesis in mice via the non-canonical Wnt pathway

Disease Models & Mechanisms ◽

10.1242/dmm.019083 ◽

2015 ◽

Vol 8 (6) ◽

pp. 527-541 ◽

Cited By ~ 21

Author(s):

Z. A. Abdelhamed ◽

S. Natarajan ◽

G. Wheway ◽

C. F. Inglehearn ◽

C. Toomes ◽

...

Keyword(s):

Basal Body ◽

Wnt Pathway ◽

Branching Morphogenesis ◽

Canonical Wnt Pathway ◽

Body Positioning ◽

Canonical Wnt ◽

Syndrome Protein

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Canonical Wnt Signaling Pathway on Polarity Formation of Utricle Hair Cells

Neural Plasticity ◽

10.1155/2021/9950533 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Di Deng ◽

Xiaoqing Qian ◽

Binjun Chen ◽

Xiaoyu Yang ◽

Yanmei Wang ◽

...

Keyword(s):

Wnt Signaling ◽

Inner Ear ◽

Signaling Pathway ◽

Hair Cells ◽

Wnt Pathway ◽

Wnt Signaling Pathway ◽

Canonical Wnt Signaling ◽

Stage Of Development ◽

Canonical Wnt Pathway ◽

Canonical Wnt

As part of the inner ear, the vestibular system is responsible for sense of balance, which consists of three semicircular canals, the utricle, and the saccule. Increasing evidence has indicated that the noncanonical Wnt/PCP signaling pathway plays a significant role in the development of the polarity of the inner ear. However, the role of canonical Wnt signaling in the polarity of the vestibule is still not completely clear. In this study, we found that canonical Wnt pathway-related genes are expressed in the early stage of development of the utricle and change dynamically. We conditionally knocked out β-catenin, a canonical Wnt signaling core protein, and found that the cilia orientation of hair cells was disordered with reduced number of hair cells in the utricle. Moreover, regulating the canonical Wnt pathway (Licl and IWP2) in vitro also affected hair cell polarity and indicated that Axin2 may be important in this process. In conclusion, our results not only confirm that the regulation of canonical Wnt signaling affects the number of hair cells in the utricle but also provide evidence for its role in polarity development.

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

Clinical medicine Oncology ◽

10.4137/cmo.s612 ◽

2008 ◽

Vol 2 ◽

pp. CMO.S612 ◽

Cited By ~ 1

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.

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Faculty Opinions recommendation of Wnt-5a inhibits the canonical Wnt pathway by promoting GSK-3-independent beta-catenin degradation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1000920.211446 ◽

2004 ◽

Author(s):

Jeffrey Axelrod

Keyword(s):

Wnt Pathway ◽

Beta Catenin ◽

Canonical Wnt Pathway ◽

Canonical Wnt

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Leptin regulates glucose homeostasis via the canonical WNT pathway

10.1101/2021.02.16.431518 ◽

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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Xwnt11 is a target of Xenopus Brachyury: regulation of gastrulation movements via Dishevelled, but not through the canonical Wnt pathway

Development ◽

10.1242/dev.127.10.2227 ◽

2000 ◽

Vol 127 (10) ◽

pp. 2227-2238 ◽

Cited By ~ 43

Author(s):

M. Tada ◽

J.C. Smith

Keyword(s):

Wnt Pathway ◽

Target Genes ◽

Dominant Negative ◽

Beta Catenin ◽

Transcription Activator ◽

Amphibian Embryo ◽

Morphogenetic Movements ◽

Canonical Wnt Pathway ◽

Canonical Wnt

Gastrulation in the amphibian embryo is driven by cells of the mesoderm. One of the genes that confers mesodermal identity in Xenopus is Brachyury (Xbra), which is required for normal gastrulation movements and ultimately for posterior mesoderm and notochord differentiation in the development of all vertebrates. Xbra is a transcription activator, and interference with transcription activation leads to an inhibition of morphogenetic movements during gastrulation. To understand this process, we have screened for downstream target genes of Brachyury (Tada, M., Casey, E., Fairclough, L. and Smith, J. C. (1998) Development 125, 3997–4006). This approach has now allowed us to isolate Xwnt11, whose expression pattern is almost identical to that of Xbra at gastrula and early neurula stages. Activation of Xwnt11 is induced in an immediate-early fashion by Xbra and its expression in vivo is abolished by a dominant-interfering form of Xbra, Xbra-En(R). Overexpression of a dominant-negative form of Xwnt11, like overexpression of Xbra-En(R), inhibits convergent extension movements. This inhibition can be rescued by Dsh, a component of the Wnt signalling pathway and also by a truncated form of Dsh which cannot signal through the canonical Wnt pathway involving GSK-3 and (beta)-catenin. Together, our results suggest that the regulation of morphogenetic movements by Xwnt11 occurs through a pathway similar to that involved in planar polarity signalling in Drosophila.

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