Affinage

WNT3

Proto-oncogene Wnt-3 · UniProt P56703

Length
355 aa
Mass
39.6 kDa
Annotated
2026-04-28
100 papers in source corpus 34 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

WNT3 is a secreted Wnt family ligand essential for vertebrate axis formation, limb development, and germ layer specification, functioning through both canonical β-catenin and non-canonical (RhoA/ROCK, MAPK/ERK) signaling pathways depending on cellular context. WNT3 undergoes Porcupine-mediated palmitoylation at conserved cysteine (C80) and serine (S212) residues and N-glycosylation at Asn90 and Asn301; palmitoylation at S212 is dispensable for secretion but required for cholesterol-dependent membrane domain association, Frizzled receptor engagement, and downstream β-catenin signaling, while N-glycosylation at Asn301 is necessary for protein stability (PMID:31803740, PMID:34124053, PMID:38994173). WNT3 binds Frizzled receptors (FZD7, FZD1) in an LRP5/6 co-receptor-dependent manner, spreads extracellularly via HSPG-modulated diffusion, and can also be transported between cells via Flotillin-2/Ror2-dependent cytonemes; its protein stability is regulated by NEDD4L-mediated ubiquitination (PMID:33236989, PMID:18313787, PMID:36040316, PMID:36597142). Homozygous loss-of-function mutations in WNT3 cause tetra-amelia syndrome in humans (PMID:14872406).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1999 High

    Establishing that Wnt3 is required for vertebrate primary axis formation resolved whether Wnt3 is essential or redundant among Wnt ligands during gastrulation.

    Evidence Wnt3-/- mouse knockout showing failure of primitive streak, mesoderm, and node formation

    PMID:10431240

    Open questions at the time
    • Tissue-specific source of Wnt3 (epiblast vs. visceral endoderm) not resolved
    • Downstream transcriptional targets not identified
    • Mechanism of ligand secretion and spread unknown
  2. 2000 Medium

    Demonstrating that Wnt3 activates a β-catenin-independent gene expression program (including COX-2 and periostin) established that Wnt3 signals through non-canonical pathways in addition to canonical β-catenin.

    Evidence Retroviral Wnt3 expression in mammary epithelial cells; antisense β-catenin and GSK3 inhibition failing to recapitulate Wnt3 target gene induction

    PMID:10884377

    Open questions at the time
    • Identity of the non-canonical pathway not determined
    • Receptor mediating β-catenin-independent signaling unknown
  3. 2003 High

    Defining Wnt3's role in AER establishment and limb patterning upstream of BMP signaling extended the gene's developmental functions beyond gastrulation to organogenesis.

    Evidence Mouse conditional β-catenin knockout in ventral ectoderm with genetic epistasis to BMP pathway

    PMID:12569130

    Open questions at the time
    • Whether Wnt3 acts directly on AER precursors or indirectly via BMP not fully resolved
  4. 2004 High

    Identification of a homozygous WNT3 nonsense mutation (Q83X) causing human tetra-amelia linked a Mendelian disease to WNT3 loss-of-function and confirmed the essential role in limb formation across species.

    Evidence Homozygosity mapping and sequencing in a consanguineous family

    PMID:14872406

    Open questions at the time
    • Genotype–phenotype spectrum for hypomorphic alleles unknown
    • Craniofacial and urogenital phenotype mechanisms not dissected
  5. 2007 High

    Resolving the tissue-specific requirement for Wnt3 in gastrulation showed that epiblast-expressed Wnt3, not visceral endoderm Wnt3, is essential for primitive streak induction, while visceral endoderm Wnt3 modulates timing.

    Evidence Chimeric embryo analyses and tissue-specific conditional Wnt3 knockout in mice

    PMID:16289026 PMID:18028899 PMID:25907228

    Open questions at the time
    • Signals initiating Wnt3 expression in the posterior visceral endoderm not identified
    • Quantitative threshold of Wnt3 required for streak induction unknown
  6. 2007 Medium

    Discovery that Wnt3 mediates cell adhesion-mediated drug resistance in myeloma via a non-canonical RhoA/ROCK pathway (insensitive to DKK-1) identified a context-specific non-canonical effector route.

    Evidence siRNA knockdown of Wnt3, Rho kinase inhibitor Y27632, DKK-1 insensitivity, co-culture adhesion assays in myeloma cells

    PMID:17575106

    Open questions at the time
    • Receptor mediating Wnt3-RhoA axis not identified
    • Whether this pathway operates in non-cancer contexts unknown
  7. 2008 High

    Establishing that Wnt3 directly binds FZD7 and that Dkk1 antagonizes Wnt3 during head morphogenesis defined the ligand–receptor pair and a negative feedback loop regulating canonical signaling.

    Evidence Co-immunoprecipitation of Wnt3-FZD7, compound Dkk1;Wnt3 heterozygous mouse genetics

    PMID:18313787 PMID:18403408

    Open questions at the time
    • Structural basis of Wnt3-FZD7 interaction not determined
    • Whether Wnt3-Dkk1 feedback operates in all Wnt3-expressing tissues unknown
  8. 2012 High

    Demonstrating that Wnt3 regulates its own expression via β-catenin during gastrulation maintenance and drives EMT/trastuzumab resistance in breast cancer consolidated Wnt3's role as both a developmental autoregulatory signal and an oncogenic driver.

    Evidence Conditional epiblast Wnt3 KO with molecular marker analysis; stable Wnt3 transfection in SKBR3 breast cancer cells with β-catenin nuclear localization, EGFR transactivation, and EMT marker analysis

    PMID:23071104 PMID:23085236

    Open questions at the time
    • Autoregulatory enhancer elements not mapped
    • Whether Wnt3-driven EMT is reversible unknown
  9. 2013 Medium

    Identification of Wnt3's non-canonical MAPK/ERK pathway activation in cerebellar granule cell progenitors and its role in definitive endoderm differentiation of hESCs showed that Wnt3 dosage specifies distinct cell fates through pathway selection.

    Evidence MEK inhibitor rescue in GCP proliferation assays; WNT3 knockdown/overexpression in multiple hESC lines with DE differentiation quantification

    PMID:24052941 PMID:24303070

    Open questions at the time
    • Mechanism of pathway selection (canonical vs. MAPK) at the receptor level not known
    • Whether Wnt3 and Wnt3a have overlapping roles in DE specification not resolved
  10. 2016 High

    Biophysical demonstration that Wnt3 associates with cholesterol-dependent membrane domains in a Porcupine/palmitoylation-dependent manner in vivo resolved how lipid modification controls Wnt3 membrane behavior and signaling competence.

    Evidence SPIM-FCS in live zebrafish embryos with Porcupine inhibitor C59 and cholesterol reduction

    PMID:27463143

    Open questions at the time
    • Which specific lipid species (palmitoleate vs. palmitate) is added not resolved by imaging
    • Whether membrane domain association is required for all Wnt3 signaling outputs unknown
  11. 2019 High

    Mutagenesis of the conserved serine palmitoylation site demonstrated that this modification is dispensable for Wnt3 secretion and initial Frizzled binding but essential for membrane domain organization and signaling activation, separating secretion from signaling competence.

    Evidence Site-directed mutagenesis of Ser palmitoylation site with β-catenin reporter assays in mammalian cells and zebrafish embryos

    PMID:31803740

    Open questions at the time
    • Structural mechanism by which palmitoylation enables signaling not determined
    • Whether cysteine-site lipidation has independent signaling functions not fully addressed
  12. 2020 High

    Quantitative biophysical measurement of Wnt3 extracellular spread showed HSPG-modulated diffusion (not free diffusion alone) and established that LRP5 co-receptor is required for Wnt3-Frizzled1 binding, defining the minimal receptor complex.

    Evidence FCS, FRAP, and FCCS in live zebrafish brain tissue with LRP5 knockdown

    PMID:33236989

    Open questions at the time
    • Whether other co-receptors (LRP6, Ror2) substitute for LRP5 in Wnt3 binding not tested
    • Binding affinities for different Frizzled family members not compared
  13. 2021 High

    Systematic mutagenesis of both lipidation sites (C80, S212) showed that either is sufficient for secretion and membrane organization, but S212 lipidation is specifically indispensable for receptor interaction and signaling, establishing a hierarchy of lipid modifications.

    Evidence C80A and S212A point mutations with FCS-based membrane assays, secretion assays, and signaling reporters in zebrafish neural tissue

    PMID:34124053

    Open questions at the time
    • Crystal structure of differentially lipidated Wnt3 not available
    • Whether the lipidation hierarchy applies to other Wnt family members unknown
  14. 2017 High

    Identification of YAP as a direct repressor at the WNT3 enhancer and Twist/Smad3 as activators at the WNT3 promoter defined upstream transcriptional logic controlling WNT3 expression in pluripotency exit and EMT.

    Evidence ChIP-seq for YAP in hESCs with CRISPR KO; ChIP for Twist at Wnt3 promoter with Smad3 inhibition in breast cancer cells

    PMID:28337662 PMID:29269485

    Open questions at the time
    • Whether YAP and Twist compete at overlapping regulatory elements unknown
    • Epigenetic regulation of the WNT3 locus not fully mapped
  15. 2022 High

    Discovery that Flotillin-2 and Ror2 regulate Wnt3-carrying cytonemes and that HNF4α is an upstream transcriptional regulator of intestinal Wnt3 expanded the mechanisms of Wnt3 transport and tissue-specific transcriptional control.

    Evidence Live-cell imaging of cytonemes with Flot2/Ror2 perturbation in gastric cancer cells; Hnf4a conditional knockout in jejunal enteroids with Wnt3a rescue

    PMID:36040316 PMID:36464209

    Open questions at the time
    • Relative contribution of cytonemes vs. diffusion to Wnt3 spread in vivo not quantified
    • Whether HNF4α directly binds the Wnt3 promoter not shown
  16. 2023 Medium

    Establishing that (P)RR stabilizes Wnt3 protein by inhibiting NEDD4L-mediated ubiquitination and that ZFX directly transactivates WNT3 in CML stem cells defined post-translational and transcriptional regulatory axes in cancer.

    Evidence Co-IP of Wnt3 with NEDD4L, ATP6AP2 knock-in mice; ChIP and luciferase for ZFX at WNT3 promoter with rescue overexpression

    PMID:36597142 PMID:37864206

    Open questions at the time
    • NEDD4L ubiquitination sites on Wnt3 not mapped
    • Whether ZFX regulation of WNT3 operates outside CML not tested
    • Whether (P)RR-mediated stabilization occurs before or after Wnt3 secretion not resolved
  17. 2024 Medium

    Demonstrating that N-glycosylation at Asn301 is required for Wnt3 protein stability and that dual glycosylation (Asn90/Asn301) is needed for FZD7 binding and signaling defined a second class of essential post-translational modification for Wnt3 function.

    Evidence Site-directed mutagenesis of N-glycosylation sites with confocal FZD7 binding assay, stability assays, and HCC cell function assays

    PMID:38994173

    Open questions at the time
    • Glycan structures at each site not characterized
    • Whether glycosylation affects Wnt3 interaction with LRP5/6 not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis of Wnt3-Frizzled-LRP complex assembly, the mechanism governing canonical vs. non-canonical pathway selection at the receptor level, and whether cytoneme- vs. diffusion-mediated transport predominates in specific tissues remain unresolved.
  • No crystal or cryo-EM structure of Wnt3 in complex with its receptor
  • Pathway selection mechanism between canonical and non-canonical routes not defined
  • In vivo quantitative comparison of transport modes lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 7 GO:0060089 molecular transducer activity 4
Localization
GO:0005576 extracellular region 4 GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 9 R-HSA-1266738 Developmental Biology 7 R-HSA-1643685 Disease 4
Partners
DKK1FLOT2FZD1FZD7LRP5NEDD4LROR2

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Wnt3 is required for primitive streak, mesoderm, and node formation in mice; Wnt3-/- embryos fail to form these structures while the epiblast continues to proliferate in an undifferentiated state, demonstrating Wnt3 is essential for vertebrate primary axis formation. Gene knockout (Wnt3-/- mice) with phenotypic analysis of gastrulation and axis formation Nature genetics High 10431240
2003 Ectodermal Wnt3/β-catenin signaling is required for establishment and maintenance of the apical ectodermal ridge (AER) in the limb; Wnt3 acts upstream of BMP signaling in AER establishment and dorsoventral limb polarity. Mouse knockout and conditional removal of beta-catenin in ventral ectoderm; genetic epistasis with BMP pathway Genes & development High 12569130
2004 A homozygous nonsense mutation (Q83X) in WNT3 causes tetra-amelia in humans, demonstrating WNT3 is required for limb formation, craniofacial, and urogenital development. Homozygosity mapping, mutation identification by sequencing in consanguineous family American journal of human genetics High 14872406
2008 Wnt3 directly interacts with Frizzled-7 (FZD7) receptor, as demonstrated by co-immunoprecipitation, leading to activation of the canonical Wnt/β-catenin pathway in hepatocellular carcinoma cells. Co-immunoprecipitation, siRNA knockdown of FZD7, TCF transcriptional reporter assay Journal of hepatology High 18313787 23552403
2007 Wnt3 mediates cell adhesion-mediated drug resistance (CAM-DR) in multiple myeloma via the Wnt/RhoA/ROCK signaling pathway (non-canonical), not the canonical Dickkopf-1-sensitive pathway; this occurs through integrin α6/β1-dependent attachment to stromal cells. siRNA knockdown of Wnt3, inhibitors of Rho kinase (Y27632) and DKK-1, co-culture adhesion assays Molecular cancer therapeutics Medium 17575106
2000 Wnt-3 infection of mouse mammary epithelial cells regulates a specific gene expression program including cyclooxygenase-2 and periostin through a β-catenin-independent pathway (since overexpression of β-catenin alone could not reproduce these effects). Retroviral infection with Wnt-3, gene expression profiling, antisense β-catenin oligonucleotides, GSK-3 inhibition The Journal of biological chemistry Medium 10884377
2008 Dkk1 antagonizes Wnt3 activity during mouse head morphogenesis; reducing Wnt3 gene dosage in Dkk1-/- embryos partially rescues the truncated head phenotype, and Wnt3 reduction downregulates Dkk1 revealing a feedback mechanism. Compound Dkk1;Wnt3 heterozygous and Dkk1-/- Wnt3+/- mouse genetics, phenotypic analysis Development (Cambridge, England) High 18403408
2005 Wnt3 expression is first localized to the posterior visceral endoderm at E5.5, not in a radial ring in the proximal epiblast as previously thought; local cell-cell interactions in the posterior egg cylinder establish localized Wnt3 expression preceding primitive streak formation. Whole-mount in situ hybridization and lineage tracing at tightly staged embryonic timepoints Developmental biology Medium 16289026
2012 Conditional inactivation of Wnt3 in the epiblast allows gastrulation to initiate but prevents its maintenance; Wnt3 regulates its own expression and that of primitive streak markers via canonical Wnt/β-catenin signaling. Conditional Cre-mediated Wnt3 knockout in epiblast, molecular marker analysis Developmental biology High 23085236
2007 Wnt3 expression in the epiblast (but not posterior visceral endoderm) is required for primitive streak induction and mesoderm formation; chimeric analyses and conditional Wnt3 removal define tissue-specific requirements. Chimeric embryo analyses, conditional Wnt3 knockout, phenotypic analysis Developmental biology High 18028899
2015 Wnt3 in the posterior visceral endoderm (extra-embryonic tissue) is required for timely formation and correct positioning of the primitive streak; embryos lacking Wnt3 in the visceral endoderm show delayed streak formation but appear normal by E9.5. Conditional Wnt3 knockout restricted to visceral endoderm, embryonic phenotype analysis Developmental biology High 25907228
2013 WNT3 inhibits cerebellar granule cell progenitor (GCP) proliferation via a non-canonical pathway activating ERK1/2 and ERK5 MAPKs (rather than β-catenin), downregulating Sonic Hedgehog target genes and Atoh1; MEK inhibition reverses WNT3's anti-proliferative effect. In vitro GCP proliferation assays, MEK inhibitor rescue, Western blot for MAPK activation, medulloblastoma mouse models PloS one Medium 24303070
2011 Astrocyte-secreted Wnt3 promotes neural stem cell (NSC) differentiation in the adult hippocampus in a paracrine manner; decline in Wnt3-secreting astrocytes with aging impairs neurogenesis, and exercise rescues neurogenesis by increasing Wnt3 levels. In vivo analysis of Wnt3-secreting astrocytes, exercise intervention, chromatin state analysis of downstream target genes FASEB journal Medium 21746862
2015 WNT3 protein is specifically expressed in trophectoderm of human blastocysts and promotes trophoblast development; WNT3 addition or GSK3 inhibition promoted EOMES expression for trophoblast fate, via membrane-associated β-catenin rather than nuclear/canonical TCF1 targets. β-catenin gain/loss-of-function in human preimplantation embryos, WNT3 protein addition, immunostaining for lineage markers Molecular human reproduction Medium 26108805
2016 SPIM-FCS analysis in live zebrafish embryos demonstrates that Wnt3 is associated with cholesterol-dependent membrane domains in vivo, and this association requires palmitoylation by Porcupine; inhibition of Porcupine reduces Wnt3 membrane-domain association and causes defective brain development. Single plane illumination microscopy-fluorescence correlation spectroscopy (SPIM-FCS), Porcupine inhibitor (C59), cholesterol reduction in live transgenic zebrafish Biophysical journal High 27463143
2019 Palmitoylation of Wnt3 at a conserved serine residue (by Porcupine) is dispensable for secretion and initial Frizzled-8 binding, but essential for Wnt3's association with ordered membrane domains and for activation of Wnt/β-catenin signaling in zebrafish embryos and mammalian cells. Site-directed mutagenesis of palmitoylation site, membrane domain organization assays, Wnt/β-catenin reporter assay in mammalian cells and zebrafish Frontiers in cell and developmental biology High 31803740
2021 Wnt3 is lipid-modified at both conserved cysteine (C80) and serine (S212) residues in zebrafish neural tissue; lipidation at either residue is sufficient for Wnt3 secretion and membrane organization, but lipid modification at S212 is indispensable for receptor interaction and signaling. Cysteine-to-alanine and serine-to-alanine point mutations (C80A, S212A), FCS-based membrane organization, secretion assays, signaling reporter Frontiers in cell and developmental biology High 34124053
2020 Wnt3 spreads extracellularly in the zebrafish brain via diffusion modified by tissue morphology and interactions with heparan sulfate proteoglycans (HSPG); Wnt3 binding to its receptor Frizzled1 requires the co-receptor LRP5, as demonstrated by fluorescence cross-correlation spectroscopy. Fluorescence correlation spectroscopy, fluorescence recovery after photobleaching (FRAP), fluorescence cross-correlation spectroscopy (FCCS), LRP5 knockdown eLife High 33236989
2017 YAP binds to the WNT3 gene enhancer in hESCs and prevents WNT3 induction by Activin/SMAD signaling, thereby maintaining pluripotency; CRISPR/Cas9 knockout of YAP enables Activin to induce Wnt3 expression, stabilize β-catenin, and cooperate with SMADs to drive cardiac mesoderm differentiation. ChIP-seq, CRISPR/Cas9 YAP knockout, luciferase reporter, directed differentiation of hESCs Genes & development High 29269485
2013 WNT3 mRNA level in hESCs correlates with and is required for definitive endoderm (DE) differentiation; WNT3 knockdown inhibits and overexpression promotes DE differentiation in a WNT3 level-dependent manner. WNT3 siRNA knockdown and overexpression in multiple hESC lines, quantitative DE differentiation assays Stem cell reports Medium 24052941
2013 Temozolomide methylates the WNT3 gene promoter in blood-brain barrier cells, reducing Wnt3 synthesis and disrupting Wnt3/GSK3/β-catenin signaling, which decreases β-catenin binding to the MDR1 promoter and lowers P-glycoprotein expression. Promoter methylation analysis, Wnt3 siRNA, β-catenin ChIP on MDR1 promoter, Pgp efflux assays in BBB cells Cellular and molecular life sciences : CMLS Medium 23771630
2022 Flotillin-2 (Flot2) together with Wnt co-receptor Ror2 determines the number and length of Wnt3-carrying cytonemes in gastric cancer cells; cytoneme-mediated Wnt3 transport between cells promotes proliferation and cell survival. Live-cell imaging of Wnt3-cytonemes, Flot2 overexpression/knockdown, Ror2 perturbation, functional proliferation/survival assays; zebrafish Wnt8a cytoneme validation eLife High 36040316
2022 HNF4α acts as an upstream transcriptional regulator of intestinal Wnt3 expression and Paneth cell differentiation; deletion of Hnf4a in jejunal enteroids reduces Wnt3, and supplementation with Wnt3a rescues cell death and transcriptional defects. Hnf4a conditional knockout in enteroids, transcriptomics, Wnt3a supplementation rescue experiment Cellular and molecular gastroenterology and hepatology Medium 36464209
2023 (Pro)renin receptor ((P)RR) inhibits NEDD4L-mediated ubiquitination of Wnt3 protein, thereby stabilizing Wnt3 and activating Wnt/β-catenin signaling to promote colorectal cancer progression. Co-immunoprecipitation of Wnt3 with NEDD4L, immunofluorescence colocalization, ATP6AP2 knock-in mice, western blot for Wnt3 ubiquitination Cell communication and signaling : CCS Medium 36597142
2024 Wnt3 is N-glycosylated at two sites (Asn90 and Asn301); mutation of Asn301 alone destabilizes Wnt3 protein, while simultaneous mutation of both sites reduces Wnt3-FZD7 binding and downstream Wnt/β-catenin signaling, as well as HCC cell proliferation and invasion. Site-directed mutagenesis of N-glycosylation sites, laser confocal microscopy for FZD7 binding, actinomycin D stability assay, western blot, cell function assays World journal of gastrointestinal oncology Medium 38994173
2017 TGF-β-induced EMT in HER2-overexpressing breast cancer cells upregulates Wnt3 via a Smad3-dependent pathway; Twist transcription factor directly occupies the Wnt3 promoter (validated by ChIP) to drive Wnt3 expression downstream of TGF-β. ChIP assay for Twist at Wnt3 promoter, Twist shRNA knockdown, ELISA for secreted Wnt3, western blot, Smad3 pathway inhibition Breast cancer research and treatment Medium 28337662
2012 Wnt3 expression in Xenopus and zebrafish activates canonical Wnt/β-catenin signaling; Wnt3 and Wnt3a together are required for induction of the mid-diencephalic organizer (MDO) in zebrafish, acting in a narrow 4-hour time window; loss of Wnt3/Wnt3a leads to apoptosis within the organizer primordium, and blocking apoptosis rescues MDO formation. Morpholino knockdown of wnt3 and wnt3a, canonical Wnt pathway pharmacological activation, apoptosis blockade rescue experiment, in situ hybridization Neural development Medium 22475147
2018 Wnt3 modulates axon regeneration in adult DRG neurons by repressing mRNA translation of the transcription factor Gata4 via binding to the Gata4 3'UTR; downregulation of Wnt3 increases axon regeneration while Gata4 knockdown reverses the enhanced regeneration caused by Wnt3 downregulation. Wnt3 overexpression and knockdown in DRG neurons in vitro and in vivo, 3'UTR binding assay, Gata4 siRNA epistasis Biochemical and biophysical research communications Medium 29567480
2023 ZFX transcriptionally regulates WNT3 in CML stem/progenitor cells (validated by ChIP and luciferase reporter assays); WNT3 activates β-catenin/c-MYC/CCND1 signaling and mediates ZFX-dependent growth and imatinib resistance; WNT3 overexpression rescues ZFX silencing phenotypes. ChIP assay, luciferase reporter, shRNA and CRISPR/dCas9 silencing, rescue overexpression, microarray Cellular & molecular biology letters Medium 37864206
2010 Human Wnt3-Frizzled1 chimera activates TCF-luciferase reporter; the Frizzled1 cytoplasmic tail (PDZ binding region) and the CRD second cysteine loop are required for Wnt3-Fz1 signaling; DKK-1 blocks the chimera's activity, implicating LRP co-receptor; the chimera promotes osteoblast and inhibits adipocyte differentiation in C3H10T1/2 cells. Wnt3-Fz1 chimera construction, deletion and point mutagenesis, TCF-luciferase reporter assay, DKK-1 inhibition, cell differentiation assays Journal of cellular biochemistry Medium 20039315
2015 Thalamic WNT3 secretion regulates neocortical ribosome composition by changing levels of Ribosomal protein L7 in polysome complexes during mid-neurogenesis, thereby controlling selective mRNA translation (including Foxp2 and Apc) to specify neocortical cell subtypes. Polysome fractionation, RNA sequencing, in vivo thalamic axon manipulation with WNT3 secretion analysis The Journal of neuroscience Medium 26245956
2012 Wnt3 overexpression in breast cancer cells (SKBR3) activates Wnt/β-catenin signaling, increases nuclear β-catenin, transactivates EGFR expression, promotes EMT-like transition (increased N-cadherin, Twist, Slug; decreased E-cadherin), and confers trastuzumab resistance; Wnt3 siRNA reverses these effects. Stable Wnt3 transfection, siRNA knockdown, western blot, β-catenin localization, invasion assays Molecular cancer research : MCR Medium 23071104
2017 Defective Wnt3 expression by post-pubertal Sertoli cells (achieved via shRNA transgenic mice) leads to subfertility and oligozoospermia with diminished expression of Connexin43, a gap-junctional molecule essential for germ cell development; FSH and testosterone regulate Wnt3 in pubertal Sertoli cells. Transgenic shRNA-mediated Wnt3 knockdown in Sertoli cells, spermatogenesis analysis, Connexin43 expression Cell and tissue research Medium 29064078

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Requirement for Wnt3 in vertebrate axis formation. Nature genetics 720 10431240
1993 Spatially restricted expression of Dlx-1, Dlx-2 (Tes-1), Gbx-2, and Wnt-3 in the embryonic day 12.5 mouse forebrain defines potential transverse and longitudinal segmental boundaries. The Journal of neuroscience : the official journal of the Society for Neuroscience 523 7687285
2009 Apoptotic cells provide an unexpected source of Wnt3 signaling to drive hydra head regeneration. Developmental cell 328 19686688
2005 Primitive streak formation in mice is preceded by localized activation of Brachyury and Wnt3. Developmental biology 236 16289026
2003 Ectodermal Wnt3/beta-catenin signaling is required for the establishment and maintenance of the apical ectodermal ridge. Genes & development 235 12569130
2012 Expression of Wnt3 activates Wnt/β-catenin pathway and promotes EMT-like phenotype in trastuzumab-resistant HER2-overexpressing breast cancer cells. Molecular cancer research : MCR 224 23071104
2004 Homozygous WNT3 mutation causes tetra-amelia in a large consanguineous family. American journal of human genetics 208 14872406
1990 Wnt-3, a gene activated by proviral insertion in mouse mammary tumors, is homologous to int-1/Wnt-1 and is normally expressed in mouse embryos and adult brain. Proceedings of the National Academy of Sciences of the United States of America 187 2162045
2008 Functional interaction between Wnt3 and Frizzled-7 leads to activation of the Wnt/beta-catenin signaling pathway in hepatocellular carcinoma cells. Journal of hepatology 153 18313787
2011 Reduction in paracrine Wnt3 factors during aging causes impaired adult neurogenesis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 135 21746862
2019 CircRNA_100367 regulated the radiation sensitivity of esophageal squamous cell carcinomas through miR-217/Wnt3 pathway. Aging 126 31851619
2001 Molecular cloning and characterization of human WNT3. International journal of oncology 113 11604997
2011 Autoregulatory and repressive inputs localize Hydra Wnt3 to the head organizer. Proceedings of the National Academy of Sciences of the United States of America 92 21576458
2008 Dkk1 and Wnt3 interact to control head morphogenesis in the mouse. Development (Cambridge, England) 89 18403408
2000 Regulation of cyclooxygenase-2 and periostin by Wnt-3 in mouse mammary epithelial cells. The Journal of biological chemistry 89 10884377
2002 Regulation of WNT3 and WNT3A mRNAs in human cancer cell lines NT2, MCF-7, and MKN45. International journal of oncology 88 11788904
2007 Wnt3/RhoA/ROCK signaling pathway is involved in adhesion-mediated drug resistance of multiple myeloma in an autocrine mechanism. Molecular cancer therapeutics 78 17575106
2007 Census of vertebrate Wnt genes: isolation and developmental expression of Xenopus Wnt2, Wnt3, Wnt9a, Wnt9b, Wnt10a, and Wnt16. Developmental dynamics : an official publication of the American Association of Anatomists 76 17436276
2019 An evolutionarily-conserved Wnt3/β-catenin/Sp5 feedback loop restricts head organizer activity in Hydra. Nature communications 73 30659200
1992 Regional expression of the Wnt-3 gene in the developing mouse forebrain in relationship to diencephalic neuromeres. Mechanisms of development 69 1363370
2013 WNT3 inhibits cerebellar granule neuron progenitor proliferation and medulloblastoma formation via MAPK activation. PloS one 61 24303070
2017 YAP repression of the WNT3 gene controls hESC differentiation along the cardiac mesoderm lineage. Genes & development 60 29269485
2016 The antidepressant roles of Wnt2 and Wnt3 in stress-induced depression-like behaviors. Translational psychiatry 60 27622936
2012 Wnt3 function in the epiblast is required for the maintenance but not the initiation of gastrulation in mice. Developmental biology 59 23085236
1994 Maintenance of Wnt-3 expression in Purkinje cells of the mouse cerebellum depends on interactions with granule cells. Development (Cambridge, England) 59 8026336
2007 Wnt3 signaling in the epiblast is required for proper orientation of the anteroposterior axis. Developmental biology 58 18028899
2022 Neuroprotective Effects of Phytochemicals against Aluminum Chloride-Induced Alzheimer's Disease through ApoE4/LRP1, Wnt3/β-Catenin/GSK3β, and TLR4/NLRP3 Pathways with Physical and Mental Activities in a Rat Model. Pharmaceuticals (Basel, Switzerland) 53 36015156
2010 Wnt-3a and Wnt-3 differently stimulate proliferation and neurogenesis of spinal neural precursors and promote neurite outgrowth by canonical signaling. Journal of neuroscience research 47 20722074
2013 Temozolomide down-regulates P-glycoprotein in human blood-brain barrier cells by disrupting Wnt3 signaling. Cellular and molecular life sciences : CMLS 46 23771630
2015 WNT3 and membrane-associated β-catenin regulate trophectoderm lineage differentiation in human blastocysts. Molecular human reproduction 45 26108805
2013 WNT3 is a biomarker capable of predicting the definitive endoderm differentiation potential of hESCs. Stem cell reports 45 24052941
2020 Circ_CHFR expedites cell growth, migration and inflammation in ox-LDL-treated human vascular smooth muscle cells via the miR-214-3p/Wnt3/β-catenin pathway. European review for medical and pharmacological sciences 44 32271446
2002 WNT3-WNT14B and WNT3A-WNT14 gene clusters (Review). International journal of molecular medicine 42 12011973
1997 Isolation of two novel WNT genes, WNT14 and WNT15, one of which (WNT15) is closely linked to WNT3 on human chromosome 17q21. Genomics 42 9441749
2015 Thalamic WNT3 Secretion Spatiotemporally Regulates the Neocortical Ribosome Signature and mRNA Translation to Specify Neocortical Cell Subtypes. The Journal of neuroscience : the official journal of the Society for Neuroscience 41 26245956
2017 A83-01 inhibits TGF-β-induced upregulation of Wnt3 and epithelial to mesenchymal transition in HER2-overexpressing breast cancer cells. Breast cancer research and treatment 40 28337662
2003 Over- and ectopic expression of Wnt3 causes progressive loss of ameloblasts in postnatal mouse incisor teeth. Connective tissue research 40 12952185
2015 Extra-embryonic Wnt3 regulates the establishment of the primitive streak in mice. Developmental biology 39 25907228
2017 miR-1247-5p functions as a tumor suppressor in human hepatocellular carcinoma by targeting Wnt3. Oncology reports 38 28586038
2014 Mesenchymal-transitioned cancer cells instigate the invasion of epithelial cancer cells through secretion of WNT3 and WNT5B. Cancer science 37 24344732
2009 MSX1 induces the Wnt pathway antagonist genes DKK1, DKK2, DKK3, and SFRP1 in neuroblastoma cells, but does not block Wnt3 and Wnt5A signalling to DVL3. Cancer letters 37 19815336
2016 The Secreted Signaling Protein Wnt3 Is Associated with Membrane Domains In Vivo: A SPIM-FCS Study. Biophysical journal 36 27463143
2012 Wnt3 and Wnt3a are required for induction of the mid-diencephalic organizer in the caudal forebrain. Neural development 36 22475147
2018 Mir-29b promotes human aortic valve interstitial cell calcification via inhibiting TGF-β3 through activation of wnt3/β-catenin/Smad3 signaling. Journal of cellular biochemistry 35 29227539
2007 Iron deficiency and NRAMP1 polymorphisms (INT4, D543N and 3'UTR) do not contribute to severity of anaemia in tuberculosis in the Indonesian population. The British journal of nutrition 34 17466092
2007 Proliferation of neural stem cells correlates with Wnt-3 protein in hypoxic-ischemic neonate rats after hyperbaric oxygen therapy. Neuroreport 32 17921881
2017 MiR 376c inhibits osteoblastogenesis by targeting Wnt3 and ARF-GEF-1 -facilitated augmentation of beta-catenin transactivation. Journal of cellular biochemistry 31 29125885
2019 Downregulation of Wnt3 Suppresses Colorectal Cancer Development Through Inhibiting Cell Proliferation and Migration. Frontiers in pharmacology 30 31632267
2016 Downregulation of human Wnt3 in gastric cancer suppresses cell proliferation and induces apoptosis. OncoTargets and therapy 29 27390525
2009 Zebrafish wnt3 is expressed in developing neural tissue. Developmental dynamics : an official publication of the American Association of Anatomists 29 19452545
2012 Functional consequences of WNT3/Frizzled7-mediated signaling in non-transformed hepatic cells. Oncogenesis 28 23552403
2018 TROAP regulates prostate cancer progression via the WNT3/survivin signalling pathways. Oncology reports 27 30431120
2015 Functional consequences of 17q21.31/WNT3-WNT9B amplification in hPSCs with respect to neural differentiation. Cell reports 26 25640183
2015 WNT3 involvement in human bladder exstrophy and cloaca development in zebrafish. Human molecular genetics 26 26105184
2005 Comparative genomics on Wnt3-Wnt9b gene cluster. International journal of molecular medicine 26 15754041
1993 Molecular cloning and chromosomal localization to 17q21 of the human WNT3 gene. Genomics 24 8244403
2025 Inhibition of neutrophil extracellular traps alleviates blood-brain barrier disruption and cognitive dysfunction via Wnt3/β-catenin/TCF4 signaling in sepsis-associated encephalopathy. Journal of neuroinflammation 23 40102948
2023 Anti-Alzheimer Activity of Combinations of Cocoa with Vinpocetine or Other Nutraceuticals in Rat Model: Modulation of Wnt3/β-Catenin/GSK-3β/Nrf2/HO-1 and PERK/CHOP/Bcl-2 Pathways. Pharmaceutics 22 37631278
2019 HBO Promotes the Differentiation of Neural Stem Cells via Interactions Between the Wnt3/β-Catenin and BMP2 Signaling Pathways. Cell transplantation 22 31694396
2017 Defective Wnt3 expression by testicular Sertoli cells compromise male fertility. Cell and tissue research 22 29064078
2004 Sonic hedgehog patterning in chick neural plate is antagonized by a Wnt3-like signal. Developmental dynamics : an official publication of the American Association of Anatomists 22 14991707
2016 Diabetes Impairs Wnt3 Protein-induced Neurogenesis in Olfactory Bulbs via Glutamate Transporter 1 Inhibition. The Journal of biological chemistry 21 27226528
2020 Wnt3 distribution in the zebrafish brain is determined by expression, diffusion and multiple molecular interactions. eLife 20 33236989
2014 Genome-wide association study and mouse expression data identify a highly conserved 32 kb intergenic region between WNT3 and WNT9b as possible susceptibility locus for isolated classic exstrophy of the bladder. Human molecular genetics 20 24852367
2024 Moscatilin inhibits vascular calcification by activating IL13RA2-dependent inhibition of STAT3 and attenuating the WNT3/β-catenin signalling pathway. Journal of advanced research 19 38432393
2018 The effects of letrozole and clomiphene citrate on ligands expression of Wnt3, Wnt7a, and Wnt8b in proliferative endometrium of women with Polycystic ovarian syndrome. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 19 29510649
2019 Overexpression of BMP‑7 reverses TGF‑β1‑induced epithelial‑mesenchymal transition by attenuating the Wnt3/β‑catenin and TGF-β1/Smad2/3 signaling pathways in HK‑2 cells. Molecular medicine reports 18 31974602
2016 Tanshinone I Enhances Neurogenesis in the Mouse Hippocampal Dentate Gyrus via Increasing Wnt-3, Phosphorylated Glycogen Synthase Kinase-3β and β-Catenin Immunoreactivities. Neurochemical research 18 27053301
2015 Variations in WNT3 gene are associated with incidence of non-syndromic cleft lip with or without cleft palate in a northeast Chinese population. Genetics and molecular research : GMR 18 26505415
2019 Cyclin D1 regulates osteoarthritis chondrocyte apoptosis via WNT3/β-catenin signalling. Artificial cells, nanomedicine, and biotechnology 17 31155960
2019 More Favorable Palmitic Acid Over Palmitoleic Acid Modification of Wnt3 Ensures Its Localization and Activity in Plasma Membrane Domains. Frontiers in cell and developmental biology 15 31803740
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2016 Discovery of Klotho peptide antagonists against Wnt3 and Wnt3a target proteins using combination of protein engineering, protein-protein docking, peptide docking and molecular dynamics simulations. Journal of enzyme inhibition and medicinal chemistry 14 27766889
2002 Molecular cloning and characterization of mouse Wnt14b, clustered with mouse Wnt3 in mouse chromosome 11. International journal of molecular medicine 14 11786923
2022 The scaffolding protein flot2 promotes cytoneme-based transport of wnt3 in gastric cancer. eLife 13 36040316
2017 NRAMP1 D543N and INT4 polymorphisms in susceptibility to pulmonary tuberculosis: A meta-analysis. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 13 28648687
2018 Wnt3 and Gata4 regulate axon regeneration in adult mouse DRG neurons. Biochemical and biophysical research communications 12 29567480
2004 Wnt3 modulates the characteristics and cobblestone area-supporting activity of human stromal cells. Experimental hematology 12 15588944
2023 Single-cell RNA sequencing of intestinal crypts reveals vital events in damage repair and the double-edged sword effect of the Wnt3/β-catenin pathway in irradiated mice. Redox biology 11 37918127
2018 Wnt3 knockdown sensitizes human non-small cell type lung cancer (NSCLC) cells to cisplatin via regulating the cell proliferation and apoptosis. European review for medical and pharmacological sciences 11 29565490
2016 Altered Expression of PRKX, WNT3 and WNT16 in Human Nodular Basal Cell Carcinoma. Anticancer research 11 27630294
2024 WNT3 promotes chemoresistance to 5-Fluorouracil in oral squamous cell carcinoma via activating the canonical β-catenin pathway. BMC cancer 10 38711026
2021 Wnt3 Is Lipidated at Conserved Cysteine and Serine Residues in Zebrafish Neural Tissue. Frontiers in cell and developmental biology 10 34124053
2020 Identification of candidate lncRNAs and circRNAs regulating WNT3/β-catenin signaling in essential hypertension. Aging 10 32392180
2020 MiR-184 directly targets Wnt3 in cardiac mesoderm differentiation of embryonic stem cells. Stem cells (Dayton, Ohio) 10 32997855
2022 The aOECs Facilitate the Neuronal Differentiation of Neural Stem Cells in the Inflammatory Microenvironment Through Up-Regulation of Bioactive Factors and Activation of Wnt3/β-Catenin Pathway. Molecular neurobiology 9 36371572
2021 WNT3 hypomethylation counteracts low activity of the Wnt signaling pathway in the placenta of preeclampsia. Cellular and molecular life sciences : CMLS 9 34608506
2023 (Pro)renin receptor promotes colorectal cancer progression through inhibiting the NEDD4L-mediated Wnt3 ubiquitination and modulating gut microbiota. Cell communication and signaling : CCS 8 36597142
2022 Yiqi Jianpi Huayu Jiedu Decoction Inhibits Metastasis of Colon Adenocarcinoma by Reversing Hsa-miR-374a-3p/Wnt3/β-Catenin-Mediated Epithelial-Mesenchymal Transition and Cellular Plasticity. Frontiers in oncology 8 35837105
2020 LncWNT3-IT affects the proliferation of Sertoli cells by regulating the expression of the WNT3 gene in goat testis. Reproduction in domestic animals = Zuchthygiene 7 32501574
2018 Association of the WNT3 polymorphisms and non-syndromic cleft lip with or without cleft palate: evidence from a meta-analysis. Bioscience reports 7 30355643
2010 Wnt3-frizzled 1 chimera as a model to study canonical Wnt signaling. Journal of cellular biochemistry 7 20039315
2023 A conserved ZFX/WNT3 axis modulates the growth and imatinib response of chronic myeloid leukemia stem/progenitor cells. Cellular & molecular biology letters 6 37864206
2010 Wnt-3 and Wnt-3a play different region-specific roles in neural crest development in avians. Cell biology international 6 19947940
2022 LINC01023 Promotes the Hepatoblastoma Tumorigenesis via miR-378a-5p/WNT3 Axis. Molecular and cellular biochemistry 5 36576714
2021 Expression of Wnt3, β-catenin and MMP-7 in gastric cancer and precancerous lesions and their correlations with Helicobacter pylori infection. Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 5 34275925
2020 Wingless ligands and beta-catenin expression in the rat endometrium: The role of Wnt3 and Wnt7a/beta-catenin pathway at the embryo-uterine interface. Molecular reproduction and development 5 32949181
2012 Amphetamine stimulates Wnt3 increases in rat nucleus accumbens. Neuroreport 5 22922600
2024 N-glycosylation of Wnt3 regulates the progression of hepatocellular carcinoma by affecting Wnt/β-catenin signal pathway. World journal of gastrointestinal oncology 4 38994173
2023 Chronic GPER activation prompted the proliferation of ileal stem cell in ovariectomized mice depending on Paneth cell-derived Wnt3. Clinical science (London, England : 1979) 4 36503938