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

Development ◽  
2000 ◽  
Vol 127 (10) ◽  
pp. 2227-2238 ◽  
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.

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

2015 ◽  
Vol 466 (2) ◽  
pp. 415-430 ◽  
Author(s):  
Cheril Tapia-Rojas ◽  
Andreas Schüller ◽  
Carolina B. Lindsay ◽  
Roxana C. Ureta ◽  
Cristóbal Mejías-Reyes ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Wnt Pathway ◽  
Target Genes ◽  
Competitive Inhibition ◽  
Wnt Signalling ◽  
Signalling Pathway ◽  
Canonical Wnt Pathway ◽  
Gsk 3Β ◽  
Canonical Wnt

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.

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.

scholarly journals Developmental Lead Exposure Alters Synaptogenesis through Inhibiting Canonical Wnt Pathway In Vivo and In Vitro

PLoS ONE ◽  
2014 ◽  
Vol 9 (7) ◽  
pp. e101894 ◽  
Author(s):  
Fan Hu ◽  
Li Xu ◽  
Zhi-Hua Liu ◽  
Meng-Meng Ge ◽  
Di-Yun Ruan ◽  
...  
Keyword(s):  
Lead Exposure ◽  
Wnt Pathway ◽  
Canonical Wnt Pathway ◽  
Canonical Wnt

scholarly journals Wnt-5a inhibits the canonical Wnt pathway by promoting GSK-3–independent β-catenin degradation

2003 ◽  
Vol 162 (5) ◽  
pp. 899-908 ◽  
Author(s):  
Lilia Topol ◽  
Xueyuan Jiang ◽  
Hosoon Choi ◽  
Lisa Garrett-Beal ◽  
Peter J. Carolan ◽  
...  
Keyword(s):  
Limb Development ◽  
Wnt Pathway ◽  
Biological Systems ◽  
Signaling Molecules ◽  
Tumor Formation ◽  
Canonical Wnt Pathway ◽  
Noncanonical Pathway ◽  
Canonical Wnt

Wnts are secreted signaling molecules that can transduce their signals through several different pathways. Wnt-5a is considered a noncanonical Wnt as it does not signal by stabilizing β-catenin in many biological systems. We have uncovered a new noncanonical pathway through which Wnt-5a antagonizes the canonical Wnt pathway by promoting the degradation of β-catenin. This pathway is Siah2 and APC dependent, but GSK-3 and β-TrCP independent. Furthermore, we provide evidence that Wnt-5a also acts in vivo to promote β-catenin degradation in regulating mammalian limb development and possibly in suppressing tumor formation.

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.

scholarly journals Efficiency of Cell Therapy to GC-Induced ONFH: BMSCs with Dkk-1 Interference Is Not Superior to Unmodified BMSCs

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Wei Zhun ◽  
Li Donghai ◽  
Yang Zhouyuan ◽  
Zhao Haiyan ◽  
Kang Pengde
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cell Therapy ◽  
Wnt Pathway ◽  
Allograft Bone ◽  
Canonical Wnt Pathway ◽  
Canonical Wnt ◽  
Dickkopf 1

Glucocorticoid-induced osteonecrosis of the femoral head (ONFH) is a hip disorder, and it threatens patients who require megadose of steroid therapies. Nowadays, no valid therapies can reverse the development of GC-induced ONFH once it occurs. Stem cell therapy to GC-induced ONFH would be a promising choice. Although the pathogenesis of GC-induced ONFH is not yet fully clear, Dickkopf-1 (Dkk-1) upregulated by excessive GC use, which hinders the canonical Wnt pathway, could be an explanation. Thus, the aim of the present work lies in investigating the efficiency of the allograft bone marrow stem cells (BMSCs) with Dkk-1 interference in preventing the progression of the GC-induced ONFH. Lentivirus-meditated Dkk-1 RNAi was introduced into BMSCs which was exposed to dexamethasone (10−6 mol/L) in vitro. This interference blocked Dkk-1 overexpression by GC and afterwards prompted the transduction of Wnt/β-catenin in which the Runx2 and PPARγ were upregulated and downregulated, respectively. Thus, the osteogenesis was promoted while adipogenesis was inhibited. In vivo, GC-induced ONFH rats were treated by allotransplantation of BMSCs with Dkk-1 interference, and the progression of the disease was prevented. However, the effects were not significantly superior to treatment with nongenetically modified or normal BMSCs.

scholarly journals A β-catenin-driven switch in TCF/LEF transcription factor binding to DNA target sites promotes commitment of mammalian nephron progenitor cells

2020 ◽  
Author(s):  
Qiuyu Guo ◽  
Albert Kim ◽  
Bin Li ◽  
Andrew Ransick ◽  
Helena Bugacov ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Wnt Pathway ◽  
Target Genes ◽  
De Novo ◽  
Feedback Regulation ◽  
Canonical Wnt Pathway ◽  
Dependent Cell ◽  
Nephron Progenitor ◽  
Canonical Wnt ◽  
Gsk3 Inhibitor

AbstractThe canonical Wnt pathway transcriptional co-activator β-catenin regulates self-renewal and differentiation of mammalian nephron progenitor cells (NPCs). We modulated β-catenin levels in NPC cultures using the GSK3 inhibitor CHIR9902 (CHIR) to examine opposing developmental actions of β-catenin. Low CHIR-mediated maintenance and expansion of NPCs is independent of direct engagement of TCF/LEF/ β-catenin transcriptional complexes at low-CHIR dependent cell-cycle targets. In contrast, in high CHIR, TCF7/LEF1/β-catenin complexes replaced TCF7L1/TCF7L2 binding on enhancers of differentiation-promoting target genes. Chromosome confirmation studies showed pre-established promoter-enhancer connections to these target genes in NPCs. High CHIR-associated de novo looping was observed in positive transcriptional feedback regulation to the canonical Wnt pathway. Thus, β-catenin’s direct transcriptional role is restricted to the induction of NPCs where rising β-catenin levels switch inhibitory TCF7L1/TCF7L2 complexes to activating LEF1/TCF7 complexes at primed gene targets poised for rapid initiation of a nephrogenic program.

scholarly journals Xwnt11 and the regulation of gastrulation in Xenopus

2000 ◽  
Vol 355 (1399) ◽  
pp. 923-930 ◽  
Author(s):  
J.C. Smith ◽  
Frank L. Conlon ◽  
Yasushi Saka ◽  
Masazumi Tada
Keyword(s):  
Cell Shape ◽  
Target Genes ◽  
Signal Transduction Pathway ◽  
Small Gtpases ◽  
Mouse Embryos ◽  
Dominant Negative ◽  
Transduction Pathway ◽  
Transcription Activator ◽  
Canonical Wnt ◽  
Future Work

The molecular basis of gastrulation is poorly understood. In this paper we address this problem by taking advantage of the observation that the transcription activator Brachyury is essential for gastrulation movements in Xenopus and mouse embryos. We infer from this observation that amongst the target genes of Brachyury are some that are involved in the regulation of gastrulation. In the course of a screen for Brachyury targets we identified Xwnt11 . Use of a dominant-negative Xwnt11 construct confirms that signalling by this class of Wnts is essential for normal gastrulation movements, and further investigation suggests that Xwnt11 signals not through the canonical Wnt signalling pathway involving GSK-3 and β-catenin but through another route, which may require small GTPases such as Rho and Rac. Future work will concentrate on elucidating the Xwnt11 signal transduction pathway and on investigating its influence on cell shape and polarity during Xenopus gastrulation.

Impact of the Canonical Wnt Pathway Activation on the Pathogenesis and Prognosis of Adamantinomatous Craniopharyngiomas

2018 ◽  
Vol 50 (07) ◽  
pp. 575-581 ◽  
Author(s):  
Carlos Jucá ◽  
Leandro Colli ◽  
Clarissa Martins ◽  
Marina Campanini ◽  
Beatriz Paixão ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Wnt Pathway ◽  
Target Genes ◽  
Disease Recurrence ◽  
Positive Staining ◽  
Mrna Levels ◽  
Canonical Wnt Pathway ◽  
Pathway Activation ◽  
Adamantinomatous Craniopharyngioma ◽  
Canonical Wnt

Abstract CTNNB1 mutations and abnormal β-catenin distribution are associated with the pathogenesis of adamantinomatous craniopharyngioma (aCP). We evaluated the expression of the canonical Wnt pathway components in aCPs and its association with CTNNB1 mutations and tumor progression. Tumor samples from 14 aCP patients and normal anterior pituitary samples from eight individuals without pituitary disease were studied. Gene expression of Wnt pathway activator (WNT4), inhibitors (SFRP1, DKK3, AXIN1, and APC), transcriptional activator (TCF7), target genes (MYC, WISP2, and, CDH1), and Wnt modulator (TP53) was evaluated by qPCR. β-Catenin, MYC, and WISP2 expression was determined by immunohistochemistry (IHC). The transcription levels of all genes studied, except APC, were higher in aCPs as compared to controls and TCF7 mRNA levels correlated with CTNNB1 mutation. CDH1 mRNA was overexpressed in tumor samples of patients with disease progression in comparison to those with stable disease. β-Catenin was positive and aberrantly distributed in 11 out of 14 tumor samples. Stronger β-catenin immunostaining associated positively with tumor progression. MYC positive staining was found in 10 out of 14 cases, whereas all aCPs were negative for WISP2. Wnt pathway genes were overexpressed in aCPs harboring CTNNB1 mutations and in patients with progressive disease. Recurrence was associated with stronger staining for β-catenin. These data suggest that Wnt pathway activation contributes to the pathogenesis and prognosis of aCPs.

scholarly journals A β-catenin-driven switch in TCF/LEF transcription factor binding to DNA target sites promotes commitment of mammalian nephron progenitor cells

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Qiuyu Guo ◽  
Albert D Kim ◽  
Bin Li ◽  
Andrew Ransick ◽  
Helena Bugacov ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Wnt Pathway ◽  
Target Genes ◽  
De Novo ◽  
Feedback Regulation ◽  
Canonical Wnt Pathway ◽  
Dependent Cell ◽  
Nephron Progenitor ◽  
Canonical Wnt ◽  
Gsk3 Inhibitor

The canonical Wnt pathway transcriptional co-activator β-catenin regulates self-renewal and differentiation of mammalian nephron progenitor cells (NPCs). We modulated β-catenin levels in NPC cultures using the GSK3 inhibitor CHIR9902 (CHIR) to examine opposing developmental actions of β-catenin. Low CHIR-mediated maintenance and expansion of NPCs is independent of direct engagement of TCF/LEF/β-catenin transcriptional complexes at low CHIR-dependent cell-cycle targets. In contrast, in high CHIR, TCF7/LEF1/β-catenin complexes replaced TCF7L1/TCF7L2 binding on enhancers of differentiation-promoting target genes. Chromosome confirmation studies showed pre-established promoter-enhancer connections to these target genes in NPCs. High CHIR-associated de novo looping was observed in positive transcriptional feedback regulation to the canonical Wnt pathway. Thus, β-catenin's direct transcriptional role is restricted to the induction of NPCs where rising β-catenin levels switch inhibitory TCF7L1/TCF7L2 complexes to activating LEF1/TCF7 complexes at primed gene targets poised for rapid initiation of a nephrogenic program.

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