| 2001 |
Human WNT6 encodes a 365-amino-acid secreted glycoprotein with an N-terminal signal peptide, WNT core domain, and RGD motif; WNT6 and WNT10A genes are clustered head-to-tail with <7 kb interval on chromosome 2q35, co-expressed in SW480 colorectal cancer cells, suggesting activation of WNT-β-catenin-TCF signaling. |
Molecular cloning, sequence characterization, Northern blot expression analysis |
Biochemical and biophysical research communications |
Medium |
11350055
|
| 2002 |
Wnt-6 expressed in the ureter bud induces kidney tubulogenesis in vitro; Wnt-6-expressing cells rescue tubulogenesis in Wnt-4 mutant embryo mesenchyme and activate Wnt-4 transcription, Pax2, Pax8, Sfrp2, and E-cadherin. Wnt-6 also induces a secondary axis in Xenopus embryos, consistent with canonical signaling. |
In vitro kidney induction assay with Wnt-6-expressing cell lines, rescue of Wnt-4 mutant mesenchyme, Xenopus secondary axis assay |
Genesis (New York, N.Y. : 2000) |
High |
11948913
|
| 2007 |
Wnt6 induces specification and epithelialization of F9 embryonal carcinoma cells to primitive endoderm via a canonical Wnt-β-catenin-Snail1 signaling cascade: β-catenin and Snail1 translocate to the nucleus, cytokeratin intermediate filaments appear, and GSK3 inhibition phenocopies Wnt6. PKA activation subsequently drives parietal endoderm EMT. |
Wnt6 conditioned medium treatment of F9 cells, LiCl (GSK3 inhibitor) treatment, immunofluorescence for β-catenin/Snail1 nuclear translocation, marker analysis |
Cellular signalling |
High |
18160257
|
| 2007 |
In chick embryos, ectodermal Wnt6 is necessary for neural crest induction and acts through the non-canonical (not β-catenin-dependent) pathway; canonical Wnt signaling instead inhibited neural crest production in chick, indicating a mechanistic divergence between amniotes and anamniotes. |
Gain- and loss-of-function (ectopic expression, inhibition) in chick embryos; assessment of canonical vs. non-canonical Wnt pathway activity |
Developmental dynamics : an official publication of the American Association of Anatomists |
Medium |
17685490
|
| 2008 |
Xenopus Wnt6 is required during organogenesis (not gastrulation) to restrict heart muscle development: loss-of-function causes abnormally large myocardium; gain-of-function of Wnt6 or activated β-catenin restricts cardiomyogenesis by repressing cardiogenic transcription factors (e.g., GATA), upstream of downstream cardiomyogenic differentiation genes. |
Loss-of-function (morpholino knockdown) and gain-of-function (mRNA injection) in Xenopus; rescue by GATA reinstatement; expression analysis of cardiogenic markers |
Developmental biology |
High |
18804460
|
| 2009 |
Coordinate Gα13-RhoA and Wnt6-β-catenin signaling is required for primitive endoderm differentiation in F9 cells: constitutively active Gα13(Q226L) or p115RhoGEF (but not RhoA(L63)) caused β-catenin nuclear translocation; canonical Wnt-β-catenin activation drives gene expression changes required for primitive endoderm, while Gα13 signaling to ERM proteins mediates cytoarchitectural changes. |
Transfection of constitutively active and dominant-negative constructs, ROCK inhibitor Y-27632, β-catenin nuclear localization assay, differentiation marker analysis |
Biochemistry and cell biology = Biochimie et biologie cellulaire |
Medium |
19767821
|
| 2011 |
Wnt6 (along with Wnt10a and Wnt10b) inhibits adipogenesis and stimulates osteoblastogenesis in mesenchymal stem cells through a β-catenin-dependent mechanism: β-catenin knockdown completely prevents these effects; among the three Wnts, endogenous Wnt6 knockdown produces the greatest increase in adipogenesis and impairment of osteoblastogenesis, identifying it as the most potent endogenous regulator of MSC fate among this group. |
Gain- and loss-of-function in ST2 cells and 3T3-L1 preadipocytes; β-catenin knockdown epistasis; differentiation assays |
Bone |
High |
21872687
|
| 2011 |
In sea urchin, maternal Wnt6 is necessary and sufficient (combined with a localized vegetal cortex Dishevelled (Dsh) signal) for endoderm specification in the endomesoderm GRN: knockdown of Wnt6 causes loss of endoderm (but not mesoderm markers); adding Wnt6 to cortex-depleted eggs rescues endoderm; ectopic activation of β-catenin, dominant-negative GSK-3β, or Dsh also rescues, confirming canonical pathway involvement. |
Wnt6 morpholino knockdown, vegetal cortex ablation + Wnt6 rescue, ectopic activation of canonical Wnt components, two sea urchin species validation |
Development (Cambridge, England) |
High |
21750039
|
| 2012 |
GATA6 and FOXA2 transcription factors directly regulate Wnt6 gene expression during extraembryonic endoderm formation: both bind the Wnt6 promoter (ChIP), overexpression of either is sufficient to induce Wnt6 expression and TCF-dependent transcription (primitive endoderm markers), and both transactivate a Wnt6 reporter construct. |
Chromatin immunoprecipitation (ChIP), overexpression studies, Wnt6 promoter reporter assay, qPCR in F9 cells |
Stem cells and development |
High |
22607194
|
| 2012 |
WNT6 expression in gastric cancer cells is transcriptionally enhanced by caveolin-1 (Cav1) via β-catenin binding to the proximal WNT6 promoter (demonstrated by epirubicin treatment increasing WNT6 promoter activity); WNT6 promotes resistance to epirubicin/doxorubicin-induced apoptosis as shown by knockdown and overexpression experiments. |
Promoter activity assay, β-catenin ChIP on WNT6 promoter, WNT6 knockdown/overexpression, cell death assays |
Oncogene |
High |
22370641
|
| 2013 |
Wnt6 in M. tuberculosis-infected macrophages induces proliferation via a pertussis toxin-sensitive, ERK-mediated, β-catenin-independent induction of c-Myc; Wnt6 also drives macrophage polarization toward M2-like phenotype (induction of Arginase-1, downregulation of TNF-α) via TLR-MyD88-NF-κB-dependent induction mechanism in bone marrow-derived macrophages. |
Wnt6 conditioned medium, Wnt6-deficient macrophages, pertussis toxin inhibition, ERK pathway analysis, Ki-67/thymidine incorporation proliferation assay, cytokine measurement |
Journal of immunology (Baltimore, Md. : 1950) |
High |
24123681
|
| 2013 |
Wnt6 is essential for stromal cell proliferation during uterine decidualization in mice: Wnt6-deficient mice show impaired stromal cell proliferation but normal decidual polyploidization; loss of Wnt6 prolongs cell cycle length by downregulating cyclin B1 expression. |
Wnt6-mutant mice, primary stromal cell culture, cell cycle analysis, cyclin B1 expression measurement |
Biology of reproduction |
High |
23175771
|
| 2014 |
WNT6 activates the JNK (c-Jun N-terminal kinase) non-canonical pathway in human dental pulp cells, promoting cell migration and differentiation (mineralization, odontogenic gene expression); JNK pathway inhibition (SP600125) reduces but does not completely abolish WNT6-induced migration and differentiation. |
WNT6 conditioned medium, JNK inhibitor SP600125, Western blot for JNK activation, RT-PCR for c-Jun, wound healing/transwell migration assays, ALP and alizarin red staining |
Journal of endodontics |
Medium |
24935540
|
| 2015 |
Sfrp2 binds Wnt6 and inhibits the Wnt6 canonical signaling pathway in cardiac progenitor cells (CPCs), suppressing CPC proliferation; this inhibition of canonical Wnt6 signaling by Sfrp2 activates the non-canonical Wnt/Planar Cell Polarity (PCP) pathway through JNK, inducing cardiac transcription factor expression and CPC differentiation. |
Sfrp2-Wnt6 binding assay, CPC treatment with Sfrp2, canonical/non-canonical pathway reporters, JNK pathway analysis, cardiac differentiation assays |
Journal of molecular and cellular cardiology |
Medium |
26071893
|
| 2016 |
Wnt6 signals through the canonical pathway in renal epithelial cells via FZD7 receptor: Wnt6 increases phosphorylation of GSK3β (Ser9), causes nuclear accumulation of β-catenin, increases TCF/Lef transcriptional activity, induces de novo tubulogenesis in 3D culture, and rescues epithelial dedifferentiation induced by TGF-β. Wnt6 also inhibits TGF-β-mediated p65-NF-κB nuclear translocation. |
Wnt6 overexpression in renal epithelial cells, GSK3β phosphorylation assay, β-catenin nuclear localization, TCF/Lef reporter assay, 3D tubulogenesis culture, TGF-β rescue experiments, p65 NF-κB translocation assay |
American journal of physiology. Renal physiology |
High |
27122540
|
| 2018 |
In Drosophila ovaries, Wnt6 ligand produced by cap cells is required to maintain anterior escort cells as a niche component: without Wnt6 signaling, anterior escort cells die, leading to loss of germline stem cells. Anterior escort cells promote DE-cadherin anchorage and transiently express the Dpp/BMP ligand to maintain full-strength BMP signaling in germline stem cells. |
Drosophila genetic manipulation (Wnt6 loss-of-function, hid-induced escort cell death), lineage analysis, in vivo imaging, BMP reporter assays |
Development (Cambridge, England) |
High |
29361569
|
| 2018 |
PLAGL2 transcriptionally activates Wnt6 in colorectal cancer cells by directly binding to the Wnt6 promoter region, thereby activating the Wnt/β-catenin pathway and promoting colorectal cancer proliferation. |
ChIP assay, dual-luciferase reporter assay, PLAGL2 knockdown in HCT116/SW480 cells, xenograft model |
Oncology reports |
Medium |
30535429
|
| 2019 |
Secreted Wnt6 binds to FZD4 receptor to activate canonical β-catenin signaling, which is upstream of ROCK1 and 14-3-3σ, mediating diabetes-associated (high glucose/AGE-induced) centrosome amplification; siRNA against Wnt6 or FZD4, and antibodies against Wnt6 or FZD4, all attenuate centrosome amplification. |
siRNA knockdown of Wnt6/FZD4/β-catenin, neutralizing antibodies against Wnt6/FZD4, β-catenin nuclear translocation assay, centrosome counting |
American journal of physiology. Cell physiology |
Medium |
31618077
|
| 2019 |
HBCD (hexabromocyclododecane) promotes adipogenesis by specifically inhibiting Wnt6 gene expression and suppressing the Wnt/β-catenin pathway at an early stage of adipogenesis (upstream of PPARγ induction), without affecting mitotic clonal expansion or C/EBPβ. |
RNA sequencing, Wnt6 expression measurement, adipogenic differentiation assays in 3T3-L1 and HPA-V cells, in vivo mouse model |
The Science of the total environment |
Medium |
31865202
|
| 2020 |
Wnt6 delivery to the amygdala of MeCP2 T158A (Rett syndrome model) mice ameliorates locomotor and social behavioral deficits; Wnt6 restores GSK-3β phosphorylation, β-catenin phosphorylation levels, and MeCP2 SUMOylation. Wnt6 increases BDNF and IGF-1 promoter activity in a dose-dependent manner. |
Lentiviral Wnt6 delivery to amygdala, behavioral assays, Western blot for GSK-3β/β-catenin/MeCP2 SUMOylation, BDNF/IGF-1 promoter reporter assay in HEK293T cells |
Scientific reports |
Medium |
31974426
|
| 2021 |
WNT6 promotes foam cell formation in M. tuberculosis-infected macrophages by upregulating acetyl-CoA carboxylase 2 (ACC2), a key lipid metabolic gene, leading to increased intracellular triacylglycerol (TAG) storage that supports Mtb survival; genetic or pharmacological loss of WNT6 or ACC2 reduces TAG levels and Mtb survival in macrophages. |
Wnt6-deficient macrophages, ACC2 pharmacological inhibition, TAG measurement, Mtb intracellular survival assay, ACC2 inhibitor + isoniazid combination in infected mice |
The Journal of clinical investigation |
High |
34255743
|
| 2021 |
In Drosophila testis, Wnt6 is required for GSC differentiation and cyst stem cell (CySC) self-renewal; mechanistically, Wnt6 downregulates Arm (β-catenin), Rac1, and Cdc42 in S2 cells, and Rac1/Cdc42 act downstream of the non-canonical Wnt pathway to regulate stem cell niche homeostasis. |
Drosophila genetic manipulation, S2 cell knockdown/overexpression, Western blot for Arm/Rac1/Cdc42, phenotypic analysis of testis niche |
Experimental cell research |
Medium |
33582096
|
| 2021 |
WNT6 promotes BMP4-driven endothelial differentiation of murine embryonic stem cells: silencing WNT6 in PA6/ES co-cultures partially impairs endothelial differentiation upon BMP4 stimulation, and this dysfunction is recovered by adding recombinant WNT6. |
Microarray gene expression, siRNA knockdown, recombinant WNT6 rescue, ES/PA6 co-culture endothelial differentiation assay |
Angiogenesis |
Medium |
34478025
|
| 2022 |
WNT6 activates β-catenin signaling in human dental papilla cells via canonical pathway (β-catenin nuclear accumulation, LEF1 upregulation, enhanced TCF/β-catenin transcriptional activity); Wnt6-induced mineralization in vivo is blocked by the Wnt/β-catenin inhibitor XAV939, confirming pathway dependence. |
Wnt6 overexpression + knockdown, immunofluorescence for β-catenin, TOPflash/FOPflash reporter assay, ALP staining, Alizarin Red staining, subcutaneous transplantation, XAV939 inhibitor treatment |
Archives of oral biology |
Medium |
35691114
|
| 2022 |
WNT6 knockdown in ovarian cancer cells inhibits proliferation, lamellipodia formation, causes cell cycle arrest, and promotes apoptosis; mechanistically, WNT6 knockdown reduces both β-catenin and Notch1 protein expression, implicating WNT6 in activation of both canonical Wnt and Notch1 pathways. |
siWNT6 knockdown in CAOV3/OVCAR3 cells, proliferation assay, cell cycle/apoptosis analysis, Western blot for β-catenin and Notch1 |
Gene |
Low |
36075327
|
| 2012 |
Sulf1A (a heparan sulfate 6-O-endosulfatase) is required for Wnt6-induced cellular hyper-elongation and inhibition of satellite cell proliferation in skeletal muscle myoblasts; neutralizing Sulf1A antibodies abolish both Wnt6-induced morphological and antiproliferative effects, indicating Sulf1A modulates Wnt6 signaling in muscle. |
Exogenous Wnt6 treatment of satellite cells on isolated fibers, Sulf1A neutralizing antibody treatment, morphological and proliferation assessment |
FEBS open bio |
Medium |
23772371
|
| 2013 |
Drosophila Wnt6 knockout flies are viable with normal wing size and planar cell polarity, but specifically lack maxillary palps; Wnt6 is absent from hemipteran genomes that also lack maxillary palps, suggesting a conserved developmental requirement. |
Wnt6 knockout fly generation (CRISPR/genetic), phenotypic analysis of wing size, planar cell polarity, and maxillary palp |
BMC biology |
Medium |
24090348
|
| 2023 |
CGRP (calcitonin gene-related peptide) regulates osteogenic differentiation of bone marrow mesenchymal stem cells through both p38 MAPK and Wnt6/β-catenin signaling pathways, as validated in vitro by demonstrating upregulation of Wnt6 expression and downstream β-catenin pathway activation upon CGRP stimulation. |
In vitro CGRP stimulation of rat BMMSCs, RNA sequencing of innervated vs. non-innervated bone grafts, osteogenic differentiation assays, Western blot for p38 MAPK and β-catenin |
Stem cells international |
Low |
37621747
|