Affinage

WNT2B

Protein Wnt-2b · UniProt Q93097

Length
391 aa
Mass
43.8 kDa
Annotated
2026-06-11
93 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

WNT2B (WNT13) is a Wnt-family ligand that drives canonical Wnt/β-catenin signaling to specify cell fate, maintain undifferentiated progenitor pools, and support tissue stem cells across multiple organs during development and regeneration (PMID:12490564, PMID:29909964). In the developing eye, WNT2B holds marginal retinal progenitors in a naive state by repressing proneural bHLH genes such as Cath5 and downregulating Notch, acting independently of cell cycle and Notch activity, and it specifies peripheral ciliary body and iris fates through β-catenin/LEF1 (PMID:15901663, PMID:16854977); this activity is restrained extracellularly by the secreted proteoglycan Tsukushi, which binds the Frizzled4 cysteine-rich domain and competes with WNT2B for receptor occupancy (PMID:21856951). WNT2B serves as an inductive signal in organ development, driving liver specification from lateral plate mesoderm, ureteric bud branching in the kidney, and forelimb initiation through a retinoic acid→Osr→Wnt2b→Tbx5/Fgf10 axis (PMID:16799568, PMID:11507767, PMID:12399308, PMID:22129829). In the intestine, mesenchymal CD90+ stromal cells are the critical WNT2B source for intestinal stem cell maintenance, and loss-of-function mutations cause severe neonatal-onset osmotic diarrhea with depleted OLFM4+ stem cells; WNT2B is non-redundant because GSK3 inhibition cannot rescue WNT2B-deficient enteroids (PMID:29909964, PMID:33097830, PMID:40654667). The locus generates multiple isoforms via alternative promoters, splicing, and translation start sites that partition between the ER/secretory pathway, mitochondria, and nucleus, with ACSL5-mediated S-palmitoylation sequestering WNT2B in mitochondria to suppress its transcriptional activity (PMID:16407296, PMID:25356045). Beyond receptor signaling, an intracellular non-secretory pool of WNT2B binds the WASHC5 spectrin-repeat domain through its middle domain, displacing WASHC1 to disrupt WASH-complex actin polymerization on endosomes, impairing ATG9A trafficking and autophagy in fibroblasts (PMID:42233622). WNT2B also modulates inflammation, activating macrophage NF-κB by competitively binding IKIP to relieve IKKβ inhibition, and human loss-of-function mutations cause Familial Hyperreninemic Hypoaldosteronism through impaired non-canonical Wnt/PCP support of the adrenal zona glomerulosa (PMID:38489235, PMID:39229119).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2002 High

    Established WNT2B as an inductive developmental signal positioned upstream of limb-identity transcription factors, defining the genetic logic of forelimb outgrowth.

    Evidence Genetic mutant, gain/loss-of-function, and epistasis experiments in zebrafish and chick placing Tbx5 downstream of Wnt to regulate Fgf10

    PMID:12399308

    Open questions at the time
    • Direct receptor for WNT2B in limb mesenchyme not identified
    • Canonical vs non-canonical pathway usage not resolved
  2. 2003 High

    Defined WNT2B as a maintainer of undifferentiated retinal progenitor cells, answering how the ciliary marginal zone stem niche is sustained.

    Evidence In ovo electroporation gain-of-function, dominant-negative LEF1 loss-of-function, and in vitro progenitor culture

    PMID:12490564

    Open questions at the time
    • Direct transcriptional targets of LEF1 not enumerated
    • Receptor identity unaddressed
  3. 2005 High

    Resolved the mechanism of progenitor maintenance, showing WNT2B suppresses proneural bHLH genes and Notch independently of Notch and cell cycle.

    Evidence Stable retinal explant overexpression, gamma-secretase Notch blockade, and Cath5 rescue

    PMID:15901663

    Open questions at the time
    • How WNT2B transcriptionally represses bHLH genes is not mechanistically dissected
  4. 2006 High

    Identified the tissue source and target tissue of WNT2B signaling in liver induction, distinguishing inductive mesoderm from responding endoderm.

    Evidence Positional cloning and genetic mosaic analysis in zebrafish

    PMID:16799568

    Open questions at the time
    • Direct downstream effectors driving hhex/prox1 in endoderm not defined
  5. 2006 High

    Revealed that WNT2B produces ER-secreted, mitochondrial, and nuclear isoforms via alternative promoters/splicing/translation, expanding the protein's potential functions beyond a secreted ligand.

    Evidence Subcellular fractionation, targeting-domain deletion mutagenesis, N-glycosylation analysis, and β-catenin/TCF reporter assays

    PMID:16407296

    Open questions at the time
    • Physiological in vivo relevance of mitochondrial/nuclear isoforms unclear
    • Mechanism by which nuclear forms increase β-catenin/TCF activity not defined
  6. 2011 High

    Established a direct extracellular antagonism mechanism, showing Tsukushi competes with WNT2B at the Frizzled4 CRD to limit progenitor expansion.

    Evidence Direct binding affinity measurement, chick in ovo overexpression, and Tsk knockout mouse phenotype

    PMID:21856951

    Open questions at the time
    • WNT2B–FZD4 binding affinity not directly measured in the same assay
    • Other Frizzled receptors not tested
  7. 2011 High

    Placed WNT2B within a defined morphogen cascade for limb initiation, ordering RA→Osr→Wnt2b→Tbx5a.

    Evidence Osr1/2 morpholino knockdown with Wnt pathway rescue and in situ hybridization in zebrafish

    PMID:22129829

    Open questions at the time
    • Mechanism by which Osr regulates wnt2b transcription not defined
  8. 2014 High

    Defined a post-translational control of WNT2B activity, showing ACSL5-dependent S-palmitoylation sequesters it in mitochondria and lowers Wnt transcriptional output.

    Evidence Modified acyl-exchange palmitoylation assay, fractionation, Wnt reporter, Apc min/+ mouse, and human tissue

    PMID:25356045

    Open questions at the time
    • Palmitoylation site(s) on WNT2B not mapped
    • Whether mitochondrial pool has any organellar function unclear
  9. 2018 High

    Established WNT2B as a non-redundant human disease gene for intestinal stem cell support, defining a Mendelian diarrheal phenotype.

    Evidence Whole-exome sequencing of patients, OLFM4 staining, enteroid culture, recombinant WNT2B rescue, and failed CHIR-99021 rescue

    PMID:29909964

    Open questions at the time
    • Why GSK3 inhibition cannot substitute for WNT2B mechanistically unexplained
    • Receptor mediating ISC support not identified
  10. 2020 High

    Identified CD90+ mesenchymal stroma as the regulated WNT2B source and placed mTORC1/L-arginine upstream of its secretion for ISC expansion.

    Evidence Mouse ISC assay, CD90+ co-culture, rapamycin inhibition, and Wnt2b neutralization

    PMID:33097830

    Open questions at the time
    • Direct link between mTORC1 and WNT2B secretion machinery undefined
  11. 2020 Medium

    Connected WNT2B to colonic regeneration and EMT, identifying FZD4 as a functional receptor and DHH as an upstream regulator in injury.

    Evidence Cytotoxin injury of colonoids, WNT2B knockdown, Hedgehog modulation; FZD4 co-localization and signaling in HT29 cells with patient tissue

    PMID:31359032 PMID:33089106

    Open questions at the time
    • FZD4 engagement shown by co-localization rather than direct binding
    • Canonical vs non-canonical output of WNT2B–FZD4 not cleanly separated
  12. 2024 Medium

    Uncovered a non-ligand inflammatory mechanism in which intracellular WNT2B competitively binds IKIP to derepress IKKβ and activate macrophage NF-κB.

    Evidence Cross-linking mass spectrometry, Co-IP, NF-κB pathway analysis, and AAV knockdown in DSS colitis mice

    PMID:38489235

    Open questions at the time
    • Single-lab interaction without reciprocal structural validation
    • How intracellular WNT2B reaches the IKK complex unclear
  13. 2024 Medium

    Assigned WNT2B a non-canonical Wnt/PCP role in the adrenal zona glomerulosa and linked human loss-of-function to Familial Hyperreninemic Hypoaldosteronism.

    Evidence Global Wnt2b knockout mice, aldosterone measurements, human genetics, and pathway analysis (preprint)

    PMID:39229119

    Open questions at the time
    • Preprint status; PCP receptor and effector not defined
    • Why this tissue uses non-canonical rather than canonical signaling unclear
  14. 2026 High

    Defined a novel intracellular function of WNT2B in autophagy, showing its middle domain displaces WASHC1 from WASHC5 to disrupt WASH-complex actin assembly and ATG9A endosomal trafficking.

    Evidence Co-IP, GST pulldown, PLA, super-resolution SIM, FRAP, ATG9A trafficking assay, and fibroblast-specific Wnt2b deletion in TNBS colitis

    PMID:42233622

    Open questions at the time
    • Balance between secretory and non-secretory WNT2B pools not quantified in vivo
    • Whether this mechanism operates outside fibroblasts unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How WNT2B isoform partitioning, receptor choice (canonical vs PCP), and its secreted vs intracellular pools are coordinated within a single cell type to produce distinct outputs remains unresolved.
  • No unified model linking isoform localization to specific receptors or pathways
  • Direct WNT2B–Frizzled binding affinities largely unmeasured
  • In vivo relevance of mitochondrial/nuclear isoforms unestablished

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0060089 molecular transducer activity 2 GO:0098772 molecular function regulator activity 2 GO:0140110 transcription regulator activity 1
Localization
GO:0005576 extracellular region 2 GO:0005739 mitochondrion 2 GO:0005634 nucleus 1 GO:0005768 endosome 1 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 3 R-HSA-9612973 Autophagy 1
Partners
ACSL5FZD4FZD7IKIPTSKUWASHC5

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 Mesodermal Wnt2b (prt/wnt2bb) signaling positively regulates liver specification in zebrafish. Positional cloning identified prt as encoding a Wnt2b homologue; mosaic analyses showed the requirement for Prt/Wnt2bb in the lateral plate mesoderm (not endoderm), acting inductively on adjacent liver-forming endoderm to drive hhex and prox1 expression. Positional cloning, genetic mosaic analysis, mutant zebrafish phenotype Nature High 16799568
2003 Wnt2b maintains undifferentiated progenitor cells in the ciliary marginal zone of the vertebrate retina. Overexpression of Wnt2b by in ovo electroporation in the central retina inhibited neuronal differentiation and induced progenitor cell markers; blocking downstream LEF1 signaling inhibited proliferation and caused premature neuronal differentiation; exogenous Wnt2b promoted proliferation of marginal progenitor cells in vitro. In ovo electroporation gain-of-function, dominant-negative LEF1 loss-of-function, in vitro progenitor cell culture assay Development High 12490564
2005 Wnt2b maintains the naive (undifferentiated) state of marginal retinal progenitor cells by downregulating multiple proneural bHLH genes (e.g., Cath5) and Notch, independently of cell cycle progression and independently of Notch activity. Stable overexpression in retinal explants inhibited differentiation even when Notch signaling was blocked; exogenous Cath5 expression suppressed the anti-differentiation effect of Wnt2b. Stable overexpression in retinal explants, gamma-secretase inhibitor Notch blockade, exogenous Cath5 rescue experiment, gene expression analysis Development High 15901663
2006 Wnt2b/β-catenin-mediated canonical Wnt signaling determines peripheral fates (ciliary body and iris) of the chick eye. Gene transfer of Wnt2b or constitutively active β-catenin into the central retina induced markers of ciliary body and iris; dominant-negative LEF1 inhibited peripheral gene expression and caused iris hypoplasia. In ovo electroporation of Wnt2b, constitutively active β-catenin, and dominant-negative LEF1; immunostaining for peripheral eye markers Development High 16854977
2002 Tbx5 and Wnt2b function together to initiate and specify forelimb outgrowth and identity. Combined mutant analyses and gain/loss-of-function experiments in zebrafish and chick showed Tbx5 functions downstream of WNT signaling to regulate Fgf10, which in turn maintains Tbx5 expression during limb outgrowth. Genetic mutant analysis, gain- and loss-of-function in zebrafish and chick, epistasis experiments Development High 12399308
2001 Wnt-2b in the mouse kidney stimulates ureter branching rather than tubule induction. Cells expressing Wnt-2b supported ureteric bud growth and branching in organ culture; recombination of Wnt-2b-pretreated ureteric bud with isolated nephrogenic mesenchyme reconstituted organogenesis. Lithium (Wnt pathway activator) phenocopied Wnt-2b in promoting ureter branching, while Wnt-4 (tubule inducer) did not. Organ culture recombination assay, isolated ureteric bud culture, lithium treatment, in situ hybridization Developmental Dynamics High 11507767
2011 The secreted proteoglycan Tsukushi (TSK) inhibits Wnt signaling by directly binding to the cysteine-rich domain of Frizzled4 (Fzd4) with an affinity of 2.3×10⁻¹⁰ M, thereby competing with Wnt2b for Fzd4 binding. TSK overexpression antagonizes Wnt2b signaling in chick retinal cells in vivo and in vitro; Tsk knockout mice show expansion of the ciliary body with upregulation of Wnt2b and Fzd4. Binding affinity measurement (direct binding assay), in ovo overexpression, Tsk knockout mouse, gene expression analysis PNAS High 21856951
2006 WNT2B produces multiple isoforms through alternative promoters, alternative RNA splicing, and alternative translation start sites. Wnt13A is N-glycosylated and localizes to the endoplasmic reticulum with minor secretion. Wnt13B (L-form) localizes predominantly to mitochondria, directed by N-terminal hydrophobic stretch (residues 1–17) and an α-helix (residues 26–50); serial deletions abolish mitochondrial targeting and redirect protein to the nucleus. S-Wnt13B and Wnt13C are nuclear forms arising from an alternative translation start at Met74. Nuclear Wnt13 forms increase β-catenin/TCF activity and increase apoptosis in endothelial cells. Subcellular fractionation, MitoTracker/HSP60 colocalization, serial deletion mutagenesis, N-glycosylation analysis, β-catenin/TCF luciferase reporter assay, apoptosis assay Journal of Biological Chemistry High 16407296
2014 ACSL5-dependent S-palmitoylation of Wnt2B causes mitochondrial accumulation of Wnt2B and decreased Wnt transcriptional activity. In the presence of ACSL5, Wnt2B was enriched in mitochondria and unable to translocate to the nucleus; ACSL5-dependent palmitoylation was identified as the molecular mechanism using a modified acyl-exchange assay. Modified acyl-exchange palmitoylation assay, subcellular fractionation, Wnt luciferase reporter assay, cell culture and mouse (Apc min/+) models, human tissue analysis World Journal of Gastroenterology High 25356045
2007 Expression of nuclear Wnt13C isoform is translationally regulated by upstream open reading frames (uORFs). The 5'-leaders of Wnt13C and Wnt13B mRNAs have an inhibitory effect on translation; mutations/deletions of upstream AUG codons (AUG-99 and AUG+1) abrogated this inhibitory effect. No internal ribosome entry site activity was detected by dicistronic reporter assays. Dicistronic reporter assay, AUG mutation/deletion analysis, stress/apoptosis treatment followed by reporter expression Biochemical and Biophysical Research Communications Medium 18155664
2018 Homozygous nonsense mutations in WNT2B cause severe neonatal-onset osmotic diarrhea associated with decreased intestinal stem cell (ISC) number (reduced OLFM4 staining) and function. WNT2B-deficient enteroids could not be expanded or passaged; recombinant murine WNT2B supplementation partially rescued enteroid survival, but CHIR-99021 (GSK3 inhibitor/canonical WNT activator) could not rescue them, indicating a non-redundant role for WNT2B in supporting ISCs. Whole-exome sequencing, intestinal biopsy histology, OLFM4 immunofluorescence, ex vivo enteroid culture, recombinant WNT2B supplementation, CHIR-99021 rescue experiment, qRT-PCR American Journal of Human Genetics High 29909964
2011 In zebrafish, Osr1 and Osr2 genes act upstream of wnt2b in the pronephric anlage to control pectoral fin (limb) bud development. Osr morphant embryos showed reduced wnt2b expression and impaired tbx5a maintenance; increasing Wnt signaling in Osr morphants partially rescued tbx5a expression. Osr genes are downstream of retinoic acid (RA) signaling, placing the RA→Osr→Wnt2b→Tbx5a axis in limb initiation. Morpholino knockdown (Osr1/2), epistasis by Wnt pathway activation rescue, in situ hybridization, zebrafish developmental analysis Development High 22129829
2020 Epithelial WNT2B is upregulated following cytotoxin-induced injury in human colonoids and is essential for colonic regeneration. Desert Hedgehog (DHH), but not Indian or Sonic Hedgehog, drives regeneration and modulates WNT2B expression in this epithelial regeneration model that lacks mesenchymal Wnts. EspP cytotoxin injury of human colonoids, WNT2B knockdown, Hedgehog pathway inhibition/activation, gene expression analysis iScience Medium 33089106
2020 L-arginine stimulates Wnt2b secretion by CD90+ intestinal stromal cells through the mTORC1 pathway, and this Wnt2b secretion is required for L-arginine-induced intestinal stem cell (ISC) expansion. Blocking Wnt2b production prevented L-arginine-induced ISC expansion in mice and organoid co-culture models. Mouse ISC expansion assay, CD90+ stromal cell co-culture, mTORC1 inhibition (rapamycin), Wnt2b neutralization, organoid experiments Communications Biology High 33097830
2017 Wnt2b attenuates hepatic stellate cell (HSC) activation and liver fibrosis by negatively regulating TLR4 signaling. Wnt2b directly suppressed LPS-induced HSC activation, inhibited TLR4-enhanced sensitivity to TGF-β, and suppressed TLR4 expression as well as NF-κB and MAPK activation downstream of TLR4. HSC activation assay, LPS stimulation, TLR4 pathway analysis (NF-κB, MAPKs), Western blotting, Wnt2b gain/loss-of-function in HSC culture Scientific Reports Medium 28638086
2021 Tumor-secreted exosomal Wnt2B is transferred from cervical cancer cells into fibroblasts to promote their activation into cancer-associated fibroblasts (CAFs) via Wnt/β-catenin signaling. Inhibiting exosomal release or the Wnt/β-catenin signaling pathway diminished fibroblast activation induced by exosomal Wnt2B. Exosome isolation and characterization, fibroblast co-culture, Wnt/β-catenin pathway inhibition, in vitro and in vivo tumor models Oncogenesis Medium 33731705
2020 WNT2b activates epithelial-mesenchymal transition (EMT) in intestinal epithelial cells (HT29) through FZD4 receptor activation. Increased WNT2b/FZD4 interaction was detected in penetrating Crohn's disease tissue versus stenotic disease, and WNT2b treatment induced EMT markers in HT29 cells in vitro. In vitro WNT2b treatment of HT29 cells, FZD4 receptor involvement assessed by co-localization and signaling assays, RT-PCR, western blotting, confocal microscopy of patient tissue Journal of Crohn's & Colitis Medium 31359032
2022 Foxf2 transcription factor represses bone formation by suppressing Wnt2b expression. Foxf2 knockdown in mouse femurs enhanced bone regeneration in vivo; RNA-seq and molecular experiments established Wnt2b as the mediator of Foxf2's effect on osteoblastic differentiation from MSCs. Osteoprogenitor-specific Foxf2 knockout mice developed high bone mass due to increased bone formation. RNA-seq, MSC osteoblastic differentiation assay, Foxf2 overexpression/knockdown, osteoprogenitor-specific knockout mice, in vivo bone regeneration Experimental & Molecular Medicine Medium 35668101
2010 Wnt2b expression at the optic cup lip requires a border between the pigmented epithelium (RPE) and non-pigmented epithelium (NPE), not lens-derived signals. Lensless optic cups expressed Wnt2b normally; ectopic RPE/NPE borders induced ectopic Wnt2b expression without lens contact; lens removal from formed optic cup caused loss of endogenous Wnt2b expression, indicating the lens is required for maintenance but not induction of Wnt2b. Microsurgical lens removal, FGF-expressing retrovirus to create ectopic RPE/NPE borders, in situ hybridization for Wnt2b in chick embryo Molecular Vision Medium 21179237
2024 WNT2B activates macrophage NF-κB signaling in inflammatory bowel disease by competitively binding to IKIP (IKK-interacting protein), reducing the IKIP–IKKβ interaction and thereby promoting IKKβ activation and downstream inflammatory cytokine expression. AAV-mediated WNT2B knockdown in intestinal macrophages reduced intestinal inflammation in DSS-treated mice. Protein cross-linking and mass spectrometry to identify IKIP as WNT2B-interacting partner, Co-IP, NF-κB pathway analysis, AAV-mediated KD in vivo, DSS colitis mouse model FASEB Journal Medium 38489235
2024 WNT2B expressed by fibroblasts binds FZD4 on NK cells, activating NF-κB and STAT3 pathways to enhance IL-33 expression; TCF4 (downstream WNT/β-catenin component) binds p65 and promotes IL-33 promoter binding. This WNT2B-driven NK cell activation induces colonic fibrosis in IBD. Salinomycin (WNT/β-catenin inhibitor) reduced IL-33 secretion and intestinal fibrosis. Co-culture of fibroblasts and NK cells, FZD4 receptor identification, NF-κB/STAT3 pathway analysis, ChIP for TCF4/p65 on IL-33 promoter, WNT2B knockdown in vivo Journal of Molecular Medicine Medium 39138828
2024 WNT2B signals through the non-canonical Wnt/planar cell polarity (PCP) pathway to regulate zona glomerulosa (zG) function and aldosterone production in the adrenal gland. Global Wnt2b knockout mice have a dysmorphic, hypocellular zG with impaired aldosterone production. Humans with WNT2B loss-of-function mutations develop a novel Familial Hyperreninemic Hypoaldosteronism (Type 4). Global Wnt2b knockout mice, adrenal histology, aldosterone measurements, human genetics (loss-of-function mutations), pathway analysis showing non-canonical PCP (not canonical β-catenin) signaling bioRxiv (preprint)preprint Medium 39229119
2026 WNT2B has a non-secretory intracellular function: its conserved middle domain (MD) binds the spectrin repeat domain (SRD) of WASHC5, competitively displacing WASHC1 and disrupting WASH complex assembly, thereby inhibiting WASHC1-mediated actin polymerization on early endosomes. This impairs endosomal cargo trafficking (including ATG9A), leading to defective autophagy initiation and accumulation of pro-inflammatory/pro-fibrotic factors in fibroblasts. A novel LC3B-II-dependent autophagic secretion pathway for WNT2B distinct from conventional ER-to-Golgi secretion was also identified. Co-IP, GST pulldown, proximity ligation assay (PLA), super-resolution structured illumination microscopy (SIM), FRAP, ATG9A trafficking assay, TNBS mouse colitis model with fibroblast-specific Wnt2b deletion, transmission electron microscopy Autophagy High 42233622
2025 Mesenchymal (not epithelial) WNT2B is the critical cellular source supporting human intestinal epithelial development. In human intestinal organoid (HIO) transplant experiments, WNT2B R69* (loss-of-function) HIOs showed partial epithelial delamination, reduced OLFM4+ crypts, and altered apical digestion protein trafficking. Recombination experiments established that lack of mesenchymal WNT2B was sufficient to elicit the intestinal developmental phenotype. Human iPSC-derived HIOs transplanted into immunocompromised mice, histology, OLFM4 immunofluorescence, bulk RNA-seq, proteomics of patient enteroids, epithelial/mesenchymal recombination experiments bioRxiv (preprint)preprint Medium 40654667
2025 In retinal organoids, canonical WNT2B–FZD7 signaling is transiently activated in retinal progenitor cells to drive retinal layer formation, followed by non-canonical WNT5A expression; these two Wnt signals sequentially orchestrate early retinal morphogenesis. Single-cell RNA sequencing of human ESC-derived retinal organoids, immunostaining for WNT2B and FZD7, transplantation into retinal degeneration rat model bioRxiv (preprint)preprint Low bio_10.1101_2025.06.20.660659
2001 WNT2B encodes two isoforms (WNT2B1 and WNT2B2) due to alternative splicing using alternative promoters. WNT2B2 mRNA is differentially regulated by β-estradiol (which downregulates WNT2B2 while transiently upregulating WNT2) and by retinoic acid in cancer cell lines. RT-PCR expression analysis in MCF-7, NT2, and MKN45 cells with hormone/cytokine treatment International Journal of Molecular Medicine Low 11712082
2024 WNT2B-deficient mice show enhanced susceptibility to DSS-induced colitis with increased early inflammatory cytokine production (elevated CXCR4 and IL-6); baseline histology is normal but intestinal stem cell markers are decreased. Human WNT2B-deficient organoids show increased IL-6 and CXCR4, and biopsy tissue shows increased neutrophils. Wnt2b knockout mice, DSS colitis model, histology, ISC marker analysis, human organoid transcriptomics, biopsy immunostaining Cellular and Molecular Gastroenterology and Hepatology Medium 38697357
2025 MUC13 promotes nasal epithelial cell repair via MEK1/2 phosphorylation and WNT2B signaling. MUC13 increased WNT2B expression, and Muc13-knockout CRS mice showed decreased WNT2B expression with increased IL-6, collagen deposition, and mucosal thinning, confirming a MUC13–WNT2B pathway in nasal mucosal homeostasis. MUC13 overexpression/siRNA knockdown in human nasal epithelial cells, MEK1/2 phosphorylation analysis, Muc13-/- mouse CRS model, WNT2B expression analysis, scratch-wound assay Journal of Allergy and Clinical Immunology Medium 40602687
2018 Wnt-2b in the intermediate hyperpallium apicale (IMHA) of chick telencephalon is required for thyroid hormone (T3)-mediated opening of the sensitive period for filial imprinting. T3 injection increased Wnt-2b mRNA in the telencephalon; pharmacological Wnt inhibition in the IMHA blocked T3-mediated recovery of the sensitive period; injection of recombinant Wnt-2b protein into the IMHA recovered the sensitive period without T3. In vivo T3 injection, Wnt pathway pharmacological inhibition (IMHA injection), recombinant Wnt-2b protein injection into IMHA, behavioral imprinting assay, qRT-PCR Hormones and Behavior Medium 29778460
2023 WNT2B deficiency in mice leads to ectopic rod photoreceptor formation in the subretinal space, observable from postnatal day 7 through 9 months. WNT2B expression is enriched in the retinal pigment epithelium (RPE) relative to whole retina. Systemic Wnt2b knockout mice (Wnt2bfl/fl × CMV-Cre), histology of retinal sections at multiple ages, fractionation/expression analysis for Wnt2b enrichment in RPE Cells Medium 37048106
2024 Lineage tracing with Wnt2b-2A-CreERT2 knock-in mice revealed that Wnt2b-expressing cells in the proepicardial organ (PEO) and epicardium differentiate into a small fraction of cardiac fibroblasts, smooth muscle cells, and mesenchymal cells, and Wnt2b-expressing PEO cells preferentially localize to the left side of the postnatal heart. Wnt2b-2A-CreERT2 knock-in and LacZ-reporter lineage tracing, tamoxifen induction at specific embryonic stages, histology, immunostaining for cardiac cell type markers Genes to Cells Medium 39109760

Source papers

Stage 0 corpus · 93 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Mesodermal Wnt2b signalling positively regulates liver specification. Nature 284 16799568
2003 Wnt2b controls retinal cell differentiation at the ciliary marginal zone. Development (Cambridge, England) 188 12490564
2002 The limb identity gene Tbx5 promotes limb initiation by interacting with Wnt2b and Fgf10. Development (Cambridge, England) 183 12399308
1996 Cloning, expression and chromosomal localization of Wnt-13, a novel member of the Wnt gene family. Oncogene 157 8761309
2006 Wnt2b/beta-catenin-mediated canonical Wnt signaling determines the peripheral fates of the chick eye. Development (Cambridge, England) 141 16854977
2021 Promotion of epithelial-mesenchymal transformation by hepatocellular carcinoma-educated macrophages through Wnt2b/β-catenin/c-Myc signaling and reprogramming glycolysis. Journal of experimental & clinical cancer research : CR 124 33407720
2002 Wnt signaling in the ovary: identification and compartmentalized expression of wnt-2, wnt-2b, and frizzled-4 mRNAs. Endocrinology 123 12072409
2001 Differential regulation of WNT2 and WNT2B expression in human cancer. International journal of molecular medicine 114 11712082
2005 Wnt2b inhibits differentiation of retinal progenitor cells in the absence of Notch activity by downregulating the expression of proneural genes. Development (Cambridge, England) 111 15901663
2013 MicroRNA-324-3p regulates nasopharyngeal carcinoma radioresistance by directly targeting WNT2B. European journal of cancer (Oxford, England : 1990) 105 23583221
2001 Induction of ureter branching as a response to Wnt-2b signaling during early kidney organogenesis. Developmental dynamics : an official publication of the American Association of Anatomists 79 11507767
2017 Up-regulated lnc-SNHG1 contributes to osteosarcoma progression through sequestration of miR-577 and activation of WNT2B/Wnt/β-catenin pathway. Biochemical and biophysical research communications 77 29108989
1999 Analysis of chicken Wnt-13 expression demonstrates coincidence with cell division in the developing eye and is consistent with a role in induction. Developmental dynamics : an official publication of the American Association of Anatomists 74 10398532
2020 Antisense oligonucleotides targeting lncRNA AC104041.1 induces antitumor activity through Wnt2B/β-catenin pathway in head and neck squamous cell carcinomas. Cell death & disease 66 32826863
1998 Structure and expression of Wnt13, a novel mouse Wnt2 related gene. Mechanisms of development 65 9545553
2017 miR-324-3p suppresses migration and invasion by targeting WNT2B in nasopharyngeal carcinoma. Cancer cell international 64 28053597
2014 miR-185-3p regulates nasopharyngeal carcinoma radioresistance by targeting WNT2B in vitro. Cancer science 62 25297925
2005 WNT2B: comparative integromics and clinical applications (Review). International journal of molecular medicine 59 16273293
2019 Long noncoding RNA LINC00707 sponges miR-370-3p to promote osteogenesis of human bone marrow-derived mesenchymal stem cells through upregulating WNT2B. Stem cell research & therapy 54 30795799
2011 Tsukushi functions as a Wnt signaling inhibitor by competing with Wnt2b for binding to transmembrane protein Frizzled4. Proceedings of the National Academy of Sciences of the United States of America 51 21856951
2009 Transcriptional regulation of WNT2B based on the balance of Hedgehog, Notch, BMP and WNT signals. International journal of oncology 49 19360354
2019 Knockdown of LncRNA SNHG7 inhibited epithelial-mesenchymal transition in prostate cancer though miR-324-3p/WNT2B axis in vitro. Pathology, research and practice 47 31324390
2021 Tumor-secreted exosomal Wnt2B activates fibroblasts to promote cervical cancer progression. Oncogenesis 43 33731705
2020 WNT2b Activates Epithelial-mesenchymal Transition Through FZD4: Relevance in Penetrating Crohn´s Disease. Journal of Crohn's & colitis 41 31359032
2017 miR-185-3p regulates the invasion and metastasis of nasopharyngeal carcinoma by targeting WNT2B in vitro. Oncology letters 38 28454443
2018 miR-577 suppresses cell proliferation and epithelial-mesenchymal transition by regulating the WNT2B mediated Wnt/β-catenin pathway in non-small cell lung cancer. Molecular medicine reports 37 30015869
2020 lncRNA RPPH1 promotes non-small cell lung cancer progression through the miR-326/WNT2B axis. Oncology letters 36 32831924
2019 MiR-338-3p Enhances Ovarian Cancer Cell Sensitivity to Cisplatin by Downregulating WNT2B. Yonsei medical journal 36 31769245
2020 Exogenous L-arginine increases intestinal stem cell function through CD90+ stromal cells producing mTORC1-induced Wnt2b. Communications biology 35 33097830
2018 The role of MiR-324-3p in polycystic ovary syndrome (PCOS) via targeting WNT2B. European review for medical and pharmacological sciences 33 29917177
2005 Molecular evolution of Wnt2b orthologs. International journal of oncology 33 15754012
2014 Modulating effects of acyl-CoA synthetase 5-derived mitochondrial Wnt2B palmitoylation on intestinal Wnt activity. World journal of gastroenterology 30 25356045
2012 Silencing Wnt2B by siRNA interference inhibits metastasis and enhances chemotherapy sensitivity in ovarian cancer. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 30 22635028
2006 Mitochondrial and nuclear forms of Wnt13 are generated via alternative promoters, alternative RNA splicing, and alternative translation start sites. The Journal of biological chemistry 27 16407296
1998 Human Wnt-13 is developmentally regulated during the differentiation of NTERA-2 pluripotent human embryonal carcinoma cells. Oncogene 27 9674702
2019 Long non-coding RNA Hottip modulates high-glucose-induced inflammation and ECM accumulation through miR-455-3p/WNT2B in mouse mesangial cells. International journal of clinical and experimental pathology 26 31934070
2014 Antitumor effects of WNT2B silencing in GLUT1 overexpressing cisplatin resistant head and neck squamous cell carcinoma. American journal of cancer research 26 25628939
2011 The Osr1 and Osr2 genes act in the pronephric anlage downstream of retinoic acid signaling and upstream of Wnt2b to maintain pectoral fin development. Development (Cambridge, England) 26 22129829
2019 MiR-145 inhibits cervical cancer progression and metastasis by targeting WNT2B by Wnt/β-catenin pathway. International journal of clinical and experimental pathology 25 31933762
2018 Neonatal-Onset Chronic Diarrhea Caused by Homozygous Nonsense WNT2B Mutations. American journal of human genetics 23 29909964
2020 Long non-coding RNA CDKN2B-AS1 regulates high glucose-induced human mesangial cell injury via regulating the miR-15b-5p/WNT2B axis. Diabetology & metabolic syndrome 21 33298110
2021 Novel variants in the stem cell niche factor WNT2B define the disease phenotype as a congenital enteropathy with ocular dysgenesis. European journal of human genetics : EJHG 19 33526876
2014 Expression of Gli1 and Wnt2B correlates with progression and clinical outcome of pancreatic cancer. International journal of clinical and experimental pathology 19 25120849
2012 Intratumoral Wnt2B expression affects tumor proliferation and survival in malignant pleural mesothelioma patients. Experimental and therapeutic medicine 18 22969998
2021 Circ_0058106 promotes proliferation, metastasis and EMT process by regulating Wnt2b/β-catenin/c-Myc pathway through miR-185-3p in hypopharyngeal squamous cell carcinoma. Cell death & disease 17 34750351
2020 MiR-449b-5p inhibits human glioblastoma cell proliferation by inactivating WNT2B/Wnt/β-catenin signaling pathway. European review for medical and pharmacological sciences 16 32495889
2022 LncRNA HOTAIR facilitates high glucose-induced mesangial cell proliferation, fibrosis and oxidative stress in diabetic nephropathy via regulating miR-147a/WNT2B axis. Diabetology & metabolic syndrome 15 35193668
2011 Adenoviral vector expressing short hairpin RNA targeting Wnt2B has an effective antitumour activity against Wnt2B2-overexpressing tumours. European journal of cancer (Oxford, England : 1990) 15 21646015
2022 Wnt2b and Wnt5a expression is highly associated with M2 TAMs in non‑small cell lung cancer. Oncology reports 14 36102318
2020 MicroRNA‑137 suppresses the proliferation, migration and invasion of cholangiocarcinoma cells by targeting WNT2B. International journal of molecular medicine 14 31985024
2020 Epithelial WNT2B and Desert Hedgehog Are Necessary for Human Colonoid Regeneration after Bacterial Cytotoxin Injury. iScience 14 33089106
2017 Wnt2b attenuates HSCs activation and liver fibrosis through negative regulating TLR4 signaling. Scientific reports 14 28638086
2022 Foxf2 represses bone formation via Wnt2b/β-catenin signaling. Experimental & molecular medicine 13 35668101
2019 Proliferation of Ovarian Granulosa Cells in Polycystic Ovarian Syndrome Is Regulated by MicroRNA-24 by Targeting Wingless-Type Family Member 2B (WNT2B). Medical science monitor : international medical journal of experimental and clinical research 13 31215527
2019 Sevoflurane Inhibited Osteosarcoma Cell Proliferation And Invasion Via Targeting miR-203/WNT2B/Wnt/β-Catenin Axis. Cancer management and research 13 31814757
2022 Circ_0000064 knockdown attenuates high glucose-induced proliferation, inflammation and extracellular matrix deposition of mesangial cells through miR-424-5p-mediated WNT2B inhibition in cell models of diabetic nephropathy. Clinical and experimental nephrology 12 35678923
2025 S aureus upregulation of MUC13 modulates mucosal remodeling in chronic rhinosinusitis via MEK1/2 and WNT2B. The Journal of allergy and clinical immunology 11 40602687
2008 Differential expression of Wnt13 isoforms during leukemic cell differentiation. Oncology reports 11 18575737
2022 High Glucose-Induced Human Kidney Cell Apoptosis and Inflammatory Injury Are Alleviated by Circ_0008529 Knockdown via Circ_0008529-Mediated miR-485-5p/WNT2B Signaling. Applied biochemistry and biotechnology 10 35913598
2020 miR-188-5p inhibits proliferation, migration, and invasion in gallbladder carcinoma by targeting Wnt2b and Smad2. The Kaohsiung journal of medical sciences 10 33236530
2024 WNT2B Deficiency Causes Enhanced Susceptibility to Colitis Due to Increased Inflammatory Cytokine Production. Cellular and molecular gastroenterology and hepatology 9 38697357
2021 Inhibited HDAC3 promotes microRNA-376c-3p to suppress malignant phenotypes of gastric cancer cells by reducing WNT2b. Genomics 9 34284078
2026 Downregulated Wnt2B Expression Suppresses Proliferation, Invasion, and Angiogenesis of Ovarian Cancer Cells Through Inhibiting the Wnt/β-Catenin Signaling Pathway. Cancer biotherapy & radiopharmaceuticals 8 35128936
2010 The expression of Wnt2b in the optic cup lip requires a border between the pigmented and nonpigmented epithelium. Molecular vision 8 21179237
2024 WNT2B high‑expressed fibroblasts induce the fibrosis of IBD by promoting NK cells secreting IL-33. Journal of molecular medicine (Berlin, Germany) 7 39138828
2024 Non-canonical Wnt signaling triggered by WNT2B drives adrenal aldosterone production. bioRxiv : the preprint server for biology 7 39229119
2018 Wnt-2b in the intermediate hyperpallium apicale of the telencephalon is critical for the thyroid hormone-mediated opening of the sensitive period for filial imprinting in domestic chicks (Gallus gallus domesticus). Hormones and behavior 7 29778460
2007 Upstream open reading frames regulate the expression of the nuclear Wnt13 isoforms. Biochemical and biophysical research communications 6 18155664
2024 WNT2B activates macrophages via NF-κB signaling pathway in inflammatory bowel disease. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 4 38489235
2024 Anti-inflammatory role of low-intensity pulsed ultrasound in inhibiting lipopolysaccharide-induced M1 polarization of RAW264.7 cells via Wnt2b/AXIN/β-catenin. PeerJ 4 39553710
2018 Expression Analysis of ACSL5 and Wnt2B in Human Congenital Pulmonary Airway Malformations. The Journal of surgical research 4 30463708
2017 Genetic Variants in WNT2B and BTRC Predict Melanoma Survival. The Journal of investigative dermatology 4 28499756
2024 Nafamostat mesylate sensitizes ovarian cancer cells to carboplatin by promoting the ZNF24-mediated inhibition of WNT2B. The Journal of toxicological sciences 3 39496384
2021 Contribution of WNT2B Genetic Variants to Ischemic Stroke Occurrence in a Chinese Han Population. Journal of cardiovascular pharmacology 3 34009855
2021 Investigations on the Role of the MicroRNA-338-5p/Wnt Family Member 2B (WNT2B) Axis in Regulating the Pathogenesis of Nasopharyngeal Carcinoma (NPC). Frontiers in oncology 3 34268117
2024 LincROR promotes tumor growth of colorectal cancer through the miR-145/WNT2B/WNT10A/Wnt/β-catenin regulatory axis. PloS one 2 39546475
2023 Ectopic Rod Photoreceptor Development in Mice with Genetic Deficiency of WNT2B. Cells 2 37048106
2023 WNT2B Deficiency Causes Increased Susceptibility to Colitis in Mice and Impairs Intestinal Epithelial Development in Humans. bioRxiv : the preprint server for biology 2 37131772
2021 miR-27b-5p inhibits BeWo cells fusion by regulating WNT2B and enzyme involved in progesterone synthesis. American journal of reproductive immunology (New York, N.Y. : 1989) 2 33639023
2025 Necrotizing enterocolitis causes increased ileal goblet cell loss in Wnt2b KO mice. bioRxiv : the preprint server for biology 1 39829885
2025 MSCs attenuate airway remodeling in HDM-induced asthma by inhibiting the Timp1-Wnt2b axis. Acta biochimica et biophysica Sinica 1 40999905
2024 Hsa_circ_0008360 promotes high glucose-induced damage in HK-2 cells via miR-346/WNT2B axis. Journal of endocrinological investigation 1 38472721
2023 [Fibroblasts overpressing WNT2b cause impairment of intestinal mucosal barrier]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 1 36946039
2017 Impact of Altered WNT2B Expression on Bladder Wall Fibroblasts: Implications for Apoptosis Regulation in the Stroma of the Lower Urinary Tract. Urologia internationalis 1 29131138
2014 [The expression and significance of miRNA-324-3p and WNT2B in nasopharyngeal carcinoma]. Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery 1 25735100
2002 Xwnt-2 (Xwnt-2b) is maternally expressed in Xenopus oocytes and embryos. Biochimica et biophysica acta 1 12084573
2026 WNT2B impairs endosomal trafficking via WASHC5 to inhibit autophagy: a novel non-secretory WNT pathway. Autophagy 0 42233622
2025 Effects of INSL3 and WNT2B gene polymorphisms on seasonal reproductive traits of Xinjiang Qira black sheep, Kazakh sheep and Duolang sheep. Animal biotechnology 0 40317716
2025 Mesenchymal WNT2B is required for the development and function of the human intestine. bioRxiv : the preprint server for biology 0 40654667
2025 Loss of WNT2B Increases Progression from Dysplasia to Colorectal Cancer. bioRxiv : the preprint server for biology 0 40909730
2025 The GABBR1/miR-19b-3p/WNT2B axis regulates insulin resistance and liver injury in diabetes with viral infection: mechanistic and therapeutic insights. Cell cycle (Georgetown, Tex.) 0 40999757
2024 Lineage tracing using Wnt2b-2A-CreERT2 knock-in mice reveals the contributions of Wnt2b-expressing cells to novel subpopulations of mesothelial/epicardial cell lineages during mouse development. Genes to cells : devoted to molecular & cellular mechanisms 0 39109760
2023 [Mechanism of intestinal injury induced by WNT2B high-expressed fibroblasts in Crohn's disease]. Zhonghua er ke za zhi = Chinese journal of pediatrics 0 37385803

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