scholarly journals When Wnts antagonize Wnts

2003 ◽  
Vol 162 (5) ◽  
pp. 753-756 ◽  
Author(s):  
Gilbert Weidinger ◽  
Randall T. Moon
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathways ◽  
Limb Bud ◽  
Zebrafish Embryos ◽  
Previous Hypothesis ◽  
Distal Mouse ◽  
Wnt Ligands ◽  
Mouse Limb ◽  
Ectopic Activation ◽  
Canonical Wnt

Secreted Wnt ligands appear to activate a variety of signaling pathways. Two papers in this issue now present genetic evidence that “noncanonical” Wnt signaling inhibits the “canonical” Wnt/β-catenin pathway. Westfall et al. (2003a) show that zebrafish embryos lacking maternal Wnt-5 function are dorsalized due to ectopic activation of β-catenin, whereas Topol et al. (2003) report that chondrogenesis in the distal mouse limb bud depends on inhibition of Wnt/β-catenin signaling by a paralogue of Wnt-5. These studies present the first genetic confirmation of the previous hypothesis that vertebrate Wnt signaling pathways can act in an antagonistic manner.

scholarly journals Wnt Signaling in Vascular Calcification

2021 ◽  
Vol 8 ◽  
Author(s):  
Kaylee Bundy ◽  
Jada Boone ◽  
C. LaShan Simpson
Keyword(s):  
Cardiovascular Disease ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Vascular Calcification ◽  
Arterial Wall ◽  
Wnt Signaling Pathway ◽  
Phenotypic Switch ◽  
Wnt Ligands ◽  
And Function ◽  
Canonical Wnt

Cardiovascular disease is a worldwide epidemic and considered the leading cause of death globally. Due to its high mortality rates, it is imperative to study the underlying causes and mechanisms of the disease. Vascular calcification, or the buildup of hydroxyapatite within the arterial wall, is one of the greatest contributors to cardiovascular disease. Medial vascular calcification is a predictor of cardiovascular events such as, but not limited to, hypertension, stiffness, and even heart failure. Vascular smooth muscle cells (VSMCs), which line the arterial wall and function to maintain blood pressure, are hypothesized to undergo a phenotypic switch into bone-forming cells during calcification, mimicking the manner by which mesenchymal stem cells differentiate into osteoblast cells throughout osteogenesis. RunX2, a transcription factor necessary for osteoblast differentiation and a target gene of the Wnt signaling pathway, has also shown to be upregulated when calcification is present, implicating that the Wnt cascade may be a key player in the transdifferentiation of VSMCs. It is important to note that the phenotypic switch of VSMCs from a healthy, contractile state to a proliferative, synthetic state is necessary in response to the vascular injury surrounding calcification. The lingering question, however, is if VSMCs acquire this synthetic phenotype through the Wnt pathway, how and why does this signaling occur? This review seeks to highlight the potential role of the canonical Wnt signaling pathway within vascular calcification based on several studies and further discuss the Wnt ligands that specifically aid in VSMC transdifferentiation.

Wnt Production in Dental Epithelium Is Crucial for Tooth Differentiation

2019 ◽  
Vol 98 (5) ◽  
pp. 580-588 ◽  
Author(s):  
Y. Xiong ◽  
Y. Fang ◽  
Y. Qian ◽  
Y. Liu ◽  
X. Yang ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathway ◽  
Tooth Development ◽  
Wnt Signaling Pathway ◽  
Conditional Knockout ◽  
Canonical Wnt Signaling ◽  
Odontoblast Differentiation ◽  
Wnt Ligands ◽  
Dental Epithelium ◽  
Canonical Wnt

The Wnt ligands display varied spatiotemporal expression in the epithelium and mesenchyme in the developing tooth. Thus far, the actions of these differentially expressed Wnt ligands on tooth development are not clear. Shh expression specifies the odontogenic epithelium during initiation and is consistently restricted to the dental epithelium during tooth development. In this study, we inactivate Wntless ( Wls), the key regulator for Wnt trafficking, by Shh-Cre to investigate how the Wnt ligands produced in the dental epithelium lineage act on tooth development. We find that conditional knockout of Wls by Shh-Cre leads to defective ameloblast and odontoblast differentiation. WlsShh-Cre teeth display reduced canonical Wnt signaling activity in the inner enamel epithelium and the underlying mesenchyme at the early bell stage, as exhibited by target gene expression and BAT-gal staining. The expression of Wnt5a and Wnt10b is not changed in WlsShh-Cre teeth. By contrast, Wnt10a expression is significantly increased in response to epithelial Wls deficiency. In addition, the expression of Hedgehog signaling pathway components Shh, Gli1, and Patched1 was greatly decreased in WlsShh-Cre teeth. Epithelial Wls loss of function in Shh lineage also leads to aberrant cell proliferation in dental epithelium and mesenchyme at embryonic day 16.5; however, the cell apoptosis is unaffected. Moreover, we find that Decorin and Col1a1, the key markers for odontoblast differentiation that are downregulated in WlsShh-Cre teeth, act as direct downstream targets of the canonical Wnt signaling pathway by chromatin immunoprecipitation analysis. Additionally, Decorin and Col1a1 expression can be increased by lithium chloride (LiCl) treatment in the in vitro tooth explants. Taken together, our results suggest that the spatial expression of Wnt ligands within the dental epithelial lineage regulates the differentiation of tooth structures in later stages.

scholarly journals Wnt Signaling in Cancer Metabolism and Immunity

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 904 ◽  
Author(s):  
Sara El-Sahli ◽  
Ying Xie ◽  
Lisheng Wang ◽  
Sheng Liu
Keyword(s):  
Wnt Signaling ◽  
Cancer Cells ◽  
Cancer Metabolism ◽  
Metabolic Reprogramming ◽  
Tumor Initiating Cells ◽  
Tumor Plasticity ◽  
Anti Cancer ◽  
Wnt Ligands ◽  
Canonical Wnt

The Wingless (Wnt)/β-catenin pathway has long been associated with tumorigenesis, tumor plasticity, and tumor-initiating cells called cancer stem cells (CSCs). Wnt signaling has recently been implicated in the metabolic reprogramming of cancer cells. Aberrant Wnt signaling is considered to be a driver of metabolic alterations of glycolysis, glutaminolysis, and lipogenesis, processes essential to the survival of bulk and CSC populations. Over the past decade, the Wnt pathway has also been shown to regulate the tumor microenvironment (TME) and anti-cancer immunity. Wnt ligands released by tumor cells in the TME facilitate the immune evasion of cancer cells and hamper immunotherapy. In this review, we illustrate the role of the canonical Wnt/β-catenin pathway in cancer metabolism and immunity to explore the potential therapeutic approach of targeting Wnt signaling from a metabolic and immunological perspective.

scholarly journals R-spondin1 regulates muscle progenitor cell fusion through control of antagonist Wnt signaling pathways

2016 ◽  
Author(s):  
Floriane Lacour ◽  
Elsa Vezin ◽  
Florian Bentzinger ◽  
Marie-Claude Sincennes ◽  
Robert D. Mitchell ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Stem Cell ◽  
Wnt Signaling ◽  
Signaling Pathways ◽  
Muscle Regeneration ◽  
Muscle Cells ◽  
Skeletal Muscle Regeneration ◽  
Acute Injury ◽  
Canonical Wnt

SUMMARYTissue regeneration requires the selective activation and repression of specific signaling pathways in stem cells. As such, the Wnt signaling pathways have been shown to control stem cell fate. In many cell types, the R-Spondin (Rspo) family of secreted proteins acts as potent activators of the canonical Wnt/β-catenin pathway. Here, we identify Rspo1 as a mediator of skeletal muscle tissue repair. Firstly we show that Rspo1-null muscles do not display any abnormalities at the basal level. However deletion of Rspo1 results in global alteration of muscle regeneration kinetics following acute injury. We found that muscle stem cells lacking Rspo1 show delayed differentiation. Transcriptome analysis further demonstrated that Rspo1 is required for the activation of Wnt/β-catenin target genes in muscle cells. Furthermore, muscle cells lacking Rspo1 fuse with a higher frequency than normal cells, leading to larger myotubes containing more nuclei both in vitro and in vivo. We found the increase in muscle fusion was dependent on up-regulation of non-canonical Wnt7a/Fzd7/Rac1 signaling. We conclude that antagonistic control of canonical and non-canonical Wnt signaling pathways by Rspo1 in muscle stem cell progeny is important for restitution of normal muscle architecture during skeletal muscle regeneration.

scholarly journals Roles of non-canonical Wnt signaling pathways in bone resorption

2018 ◽  
Vol 60 (2) ◽  
pp. 31-35 ◽  
Author(s):  
Yasuhiro Kobayashi ◽  
Shunsuke Uehara ◽  
Nobuyuki Udagawa
Keyword(s):  
Bone Resorption ◽  
Wnt Signaling ◽  
Signaling Pathways ◽  
Canonical Wnt Signaling ◽  
Canonical Wnt

scholarly journals Wnt Signaling in Red Blood Cells

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4806-4806
Author(s):  
Rina Rosin-Arbesfeld ◽  
Michal Caspi ◽  
Ronen Siman-Tov ◽  
Yakir Levi ◽  
Chava Perry
Keyword(s):  
Life Span ◽  
Wnt Signaling ◽  
Red Blood Cells ◽  
Signaling Pathway ◽  
Blood Cells ◽  
Wnt Signaling Pathway ◽  
Signaling Cascades ◽  
Canonical Wnt Signaling ◽  
Wnt Ligands ◽  
Canonical Wnt

Abstract Introduction : Red blood cells (RBCs) are the most common cell type in the human body. These cells deliver oxygen to the body's tissues and are composed of a cytoplasm that is rich in hemoglobin and is surrounded by a membrane that is essential for the cells function by providing properties such as stability and deformability. The membrane is composed of a lipid bilayer, transmembrane proteins, and a filamentous meshwork of proteins such as actin and adducin that forms the cells cytoskeleton along the entire cytoplasmic surface of the membrane. RBCs lack a nucleus and other cellular organelles that enable gene expression. Thus, it has been assumed, that signaling cascades such as the Wnt signaling pathway are not active in RBCs. The Wnt pathways are fundamental for normal development and homeostasis and regulate, among other, cell growth, motility and differentiation. Although there is no functional data connecting between Wnt signaling and RBCs, previous proteomic studies have shown that some of the non-canonical Wnt signaling components, such as specific small GTPases and kinases are present in RBCs. In this study, we show for the first time that Wnt ligands activate signaling cascades in RBCs. Methods : RBCs were collect from healthy donors and treated with different Wnt ligands. A large number of methods were used to evaluate the RBCs morphological properties, life span, vitality, flexibility and protein expression patterns. Results : Our results clearly show that different Wnt ligands can dramatically increase the live span of RBCs by affecting the cells membrane cytoskeleton. Some of the Wnts affects include activation of GTPases such as Rac, JNK and RhoA, which lead to actin modification. These changes in the actin cytoskeleton result in increased membrane stability. In parallel, treating RBCs with Wnts leads to activation of PKC and RhoA resulting in phosphorylation of adducin which in turn increases the cells membrane flexibility and improves the vitality of the cell. Summary : Our novel findings indicate that the non-canonical Wnt signaling pathway in RBCs is active and can stabilize the RBCs cytoskeleton enhancing the vitality, deformability and life span of the cell. These novel findings may help in the development of new therapeutic strategies for people suffering from different hemolytic disease that effect the RBCs cytoskeleton and provide new insights into the improvement of stored RBC units. Disclosures No relevant conflicts of interest to declare.

scholarly journals R-Spondin Family Members Regulate the Wnt Pathway by a Common Mechanism

2008 ◽  
Vol 19 (6) ◽  
pp. 2588-2596 ◽  
Author(s):  
Kyung-Ah Kim ◽  
Marie Wagle ◽  
Karolyn Tran ◽  
Xiaoming Zhan ◽  
Melissa A. Dixon ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Wnt Pathway ◽  
Expression Patterns ◽  
Family Members ◽  
Wnt Signaling Pathway ◽  
Direct Consequence ◽  
Common Mechanism ◽  
Wnt Ligands ◽  
Canonical Wnt

The R-Spondin (RSpo) family of secreted proteins is implicated in the activation of the Wnt signaling pathway. Despite the high structural homology between the four members, expression patterns and phenotypes in knockout mice have demonstrated striking differences. Here we dissected and compared the molecular and cellular function of all RSpo family members. Although all four RSpo proteins activate the canonical Wnt pathway, RSpo2 and 3 are more potent than RSpo1, whereas RSpo4 is relatively inactive. All RSpo members require Wnt ligands and LRP6 for activity and amplify signaling of Wnt3A, Wnt1, and Wnt7A, suggesting that RSpo proteins are general regulators of canonical Wnt signaling. Like RSpo1, RSpo2-4 antagonize DKK1 activity by interfering with DKK1 mediated LRP6 and Kremen association. Analysis of RSpo deletion mutants indicates that the cysteine-rich furin domains are sufficient and essential for the amplification of Wnt signaling and inhibition of DKK1, suggesting that Wnt amplification by RSpo proteins may be a direct consequence of DKK1 inhibition. Together, these findings indicate that RSpo proteins modulate the Wnt pathway by a common mechanism and suggest that coexpression with specific Wnt ligands and DKK1 may determine their biological specificity in vivo.

Non-canonical Wnt signaling pathways in hematopoiesis

2009 ◽  
Vol 46 (1-3) ◽  
pp. 155-164 ◽  
Author(s):  
Kathleen Kokolus ◽  
Michael J. Nemeth
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathways ◽  
Canonical Wnt Signaling ◽  
Canonical Wnt

scholarly journals Toxic tubular injury in kidneys from Pkd1-deletion mice accelerates cystogenesis accompanied by dysregulated planar cell polarity and canonical Wnt signaling pathways

2009 ◽  
Vol 18 (14) ◽  
pp. 2532-2542 ◽  
Author(s):  
H. Happe ◽  
W. N. Leonhard ◽  
A. van der Wal ◽  
B. van de Water ◽  
I. S. Lantinga-van Leeuwen ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathways ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Tubular Injury ◽  
Canonical Wnt Signaling ◽  
Canonical Wnt
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