scholarly journals Ror2-mediated non-canonical Wnt signaling regulates Cdc42 and cell proliferation during tooth root development

Development ◽  
2020 ◽  
pp. dev.196360
Author(s):  
Yuanyuan Ma ◽  
Junjun Jing ◽  
Jifan Feng ◽  
Yuan Yuan ◽  
Quan Wen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Wnt Signaling ◽  
Root Development ◽  
Critical Role ◽  
Canonical Wnt Signaling ◽  
Dental Tissue ◽  
Tooth Formation ◽  
Size And Shape ◽  
Dental Tissue Engineering ◽  
Canonical Wnt

The control of size and shape is an important part of regulatory process during organogenesis. Tooth formation is a highly complex process that fine-tunes the size and shape of the tooth, which are crucial for its physiological functions. Each tooth consists of a crown and one or more roots. Despite comprehensive knowledge of the mechanism that regulates early tooth crown development, we have limited understanding of the mechanism regulating root patterning and size during development. Here we show that Ror2 mediated non-canonical Wnt signaling in the dental mesenchyme plays a critical role in cell proliferation and thereby regulates root development size in mouse molars. Furthermore, Cdc42 acts as a potential downstream mediator of Ror2 signaling in root formation. Importantly, activation of Cdc42 can restore cell proliferation and partially rescue the root development size defects in Ror2 mutant mice. Collectively, our findings provide novel insights into the function of Ror2-mediated non-canonical Wnt signaling in regulating tooth morphogenesis and suggest potential avenues for dental tissue engineering.

scholarly journals The Significance of the Dysregulation of Canonical Wnt Signaling in Head and Neck Squamous Cell Carcinomas

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 723 ◽  
Author(s):  
Jarosław Paluszczak
Keyword(s):  
Cell Proliferation ◽  
Head And Neck Cancer ◽  
Wnt Signaling ◽  
Head And Neck ◽  
Neck Cancer ◽  
Squamous Cell ◽  
Wnt Signaling Pathway ◽  
Squamous Cell Carcinomas ◽  
Canonical Wnt Signaling ◽  
Canonical Wnt

The knowledge about the molecular alterations which are found in head and neck squamous cell carcinomas (HNSCC) has much increased in recent years. However, we are still awaiting the translation of this knowledge to new diagnostic and therapeutic options. Among the many molecular changes that are detected in head and neck cancer, the abnormalities in several signaling pathways, which regulate cell proliferation, cell death and stemness, seem to be especially promising with regard to the development of targeted therapies. Canonical Wnt signaling is a pathway engaged in the formation of head and neck tissues, however it is not active in adult somatic mucosal cells. The aim of this review paper is to bring together significant data related to the current knowledge on the mechanisms and functional significance of the dysregulation of the Wnt/β-catenin pathway in head and neck tumors. Research evidence related to the role of Wnt signaling activation in the stimulation of cell proliferation, migration and inhibition of apoptosis in HNSCC is presented. Moreover, its role in promoting stemness traits in head and neck cancer stem-like cells is described. Evidence corroborating the hypothesis that the Wnt signaling pathway is a very promising target of novel therapeutic interventions in HNSCC is also discussed.

scholarly journals The Microphthalmia-Associated Transcription Factor Mitf Interacts with β-Catenin To Determine Target Gene Expression

2006 ◽  
Vol 26 (23) ◽  
pp. 8914-8927 ◽  
Author(s):  
Alexander Schepsky ◽  
Katja Bruser ◽  
Gunnar J. Gunnarsson ◽  
Jane Goodall ◽  
Jón H. Hallsson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Critical Role ◽  
Wnt Signaling Pathway ◽  
Feedback Mechanism ◽  
Canonical Wnt Signaling ◽  
Melanocyte Stem Cells ◽  
Canonical Wnt

ABSTRACT Commitment to the melanocyte lineage is characterized by the onset of expression of the microphthalmia-associated transcription factor (Mitf). This transcription factor plays a fundamental role in melanocyte development and maintenance and seems to be crucial for the survival of malignant melanocytes. Furthermore, Mitf has been shown to be involved in cell cycle regulation and to play important functions in self-renewal and maintenance of melanocyte stem cells. Although little is known about how Mitf regulates these various processes, one possibility is that Mitf interacts with other regulators. Here we show that Mitf can interact directly with β-catenin, the key mediator of the canonical Wnt signaling pathway. The Wnt signaling pathway plays a critical role in melanocyte development and is intimately involved in triggering melanocyte stem cell proliferation. Significantly, constitutive activation of this pathway is a feature of a number of cancers including malignant melanoma. Here we show that Mitf can redirect β-catenin transcriptional activity away from canonical Wnt signaling-regulated genes toward Mitf-specific target promoters to activate transcription. Thus, by a feedback mechanism, Mitf can diversify the output of canonical Wnt signaling to enhance the repertoire of genes regulated by β-catenin. Our results reveal a novel mechanism by which Wnt signaling and β-catenin activate gene expression, with significant implications for our understanding of both melanocyte development and melanoma.

scholarly journals Rac1 modulates mammalian lung branching morphogenesis in part through canonical Wnt signaling

2016 ◽  
Vol 311 (6) ◽  
pp. L1036-L1049 ◽  
Author(s):  
Soula Danopoulos ◽  
Michael Krainock ◽  
Omar Toubat ◽  
Matthew Thornton ◽  
Brendan Grubbs ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Wnt Signaling ◽  
Branching Morphogenesis ◽  
Mouse Lung ◽  
Canonical Wnt Signaling ◽  
Embryonic Mouse ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Canonical Wnt ◽  
Lung Branching

Lung branching morphogenesis relies on a number of factors, including proper epithelial cell proliferation and differentiation, cell polarity, and migration. Rac1, a small Rho GTPase, orchestrates a number of these cellular processes, including cell proliferation and differentiation, cellular alignment, and polarization. Furthermore, Rac1 modulates both noncanonical and canonical Wnt signaling, important pathways in lung branching morphogenesis. Culture of embryonic mouse lung explants in the presence of the Rac1 inhibitor (NSC23766) resulted in a dose-dependent decrease in branching. Increased cell death and BrdU uptake were notably seen in the mesenchyme, while no direct effect on the epithelium was observed. Moreover, vasculogenesis was impaired following Rac1 inhibition as shown by decreased Vegfa expression and impaired LacZ staining in Flk1-Lacz reporter mice. Rac1 inhibition decreased Fgf10 expression in conjunction with many of its associated factors. Moreover, using the reporter lines TOPGAL and Axin2-LacZ, there was an evident decrease in canonical Wnt signaling in the explants treated with the Rac1 inhibitor. Activation of canonical Wnt pathway using WNT3a or WNT7b only partially rescued the branching inhibition. Moreover, these results were validated on human explants, where Rac1 inhibition resulted in impaired branching and decreased AXIN2 and FGFR2b expression. We therefore conclude that Rac1 regulates lung branching morphogenesis, in part through canonical Wnt signaling. However, the exact mechanisms by which Rac1 interacts with canonical Wnt in human and mouse lung requires further investigation.

scholarly journals Modulation of the canonical Wnt activity by androgen signaling in prostate epithelial basal stem cells

2020 ◽  
Author(s):  
Yueli Liu ◽  
Jiawen Wang ◽  
Corrigan Horton ◽  
Sol Katzman ◽  
Tao Cai ◽  
...  
Keyword(s):  
Stem Cell ◽  
Wnt Signaling ◽  
Target Genes ◽  
Critical Role ◽  
Gene Set Enrichment Analysis ◽  
Dependent Manner ◽  
Basal Cells ◽  
Canonical Wnt Signaling ◽  
Cell Functions ◽  
Canonical Wnt

AbstractBoth the canonical Wnt signaling and androgen signaling are important factors regulating prostate organogenesis. How these two pathways crosstalk to regulate prostate stem cell functions remain unclear. Here, we show that while canonical Wnt activity is required for prostate basal stem cell multipotency in vivo, ectopic Wnt activity does not promote basal-to-luminal cell differentiation. We provide evidence that androgen signaling may keep Wnt activity in check. In prostate organoid culture from basal cells, dihydrotestosterone (DHT) antagonizes R-spondin-stimulated organoid growth in a concentration-dependent manner. Molecular analyses of organoids under different treatment conditions showed that androgen signaling down-regulated the expressions of a Wnt reporter as well as many Wnt target genes. Pathway analysis and gene set enrichment analysis of organoid RNA-seq data also revealed the canonical Wnt signaling as a key pathway distinguishing organoids treated with or without DHT. Notably, DHT treatment enhanced AR and β–catenin binding in the nuclei of prostate organoids, providing possible mechanistic clues. Our results reveal a critical role of AR signaling in modulating canonical Wnt activity in prostate basal cells to regulate their multipotency.

scholarly journals Heparan sulfate on intestinal epithelial cells plays a critical role in intestinal crypt homeostasis via Wnt/β-catenin signaling

2013 ◽  
Vol 305 (3) ◽  
pp. G241-G249 ◽  
Author(s):  
Shuji Yamamoto ◽  
Hiroshi Nakase ◽  
Minoru Matsuura ◽  
Yusuke Honzawa ◽  
Kayoko Matsumura ◽  
...  
Keyword(s):  
Heparan Sulfate ◽  
Wnt Signaling ◽  
Binding Affinity ◽  
Target Genes ◽  
Glycogen Synthase ◽  
Critical Role ◽  
Intestinal Epithelial ◽  
Canonical Wnt Signaling ◽  
Small Intestinal ◽  
Canonical Wnt

Heparan sulfate (HS), a constituent of HS proteoglycans (HSPGs), is a linear polysaccharide present on the cell surface. HSPGs modulate functions of several growth factors and signaling molecules. We examined whether small intestinal epithelial HS plays some roles in crypt homeostasis using intestinal epithelium cell (IEC)-specific HS-deficient C57Bl/6 mice. Survival rate after total body irradiation was significantly reduced in HS-deficient mice due to profound intestinal injury. HS-deficient IECs exhibited Wnt/β-catenin pathway disruption, decreased levels of β-catenin nuclear localization, and reduced expression of Wnt target genes, including Lgr5 during crypt regeneration. Moreover, epithelial HS increased Wnt binding affinity of IECs, promoted phosphorylation of Wnt coreceptor LRP6, and enhanced Wnt/β-catenin signaling following ex vivo stimulation with Wnt3a, whereas activation of canonical Wnt signaling following direct inhibition of glycogen synthase kinase-3β by lithium chloride was similar between HS-deficient and wild-type mice. Thus HS influences the binding affinity of IECs to Wnt, thereby promoting activation of canonical Wnt signaling and facilitating regeneration of small intestinal crypts after epithelial injury.

scholarly journals Phosphatidylinositol 3-Kinase–Akt Pathway Plays a Critical Role in Early Cardiomyogenesis by Regulating Canonical Wnt Signaling

2005 ◽  
Vol 97 (2) ◽  
pp. 144-151 ◽  
Author(s):  
Atsuhiko T. Naito ◽  
Hiroshi Akazawa ◽  
Hiroyuki Takano ◽  
Tohru Minamino ◽  
Toshio Nagai ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Critical Role ◽  
Akt Pathway ◽  
Phosphatidylinositol 3 Kinase ◽  
Canonical Wnt Signaling ◽  
Canonical Wnt ◽  
Phosphatidylinositol 3
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