Affinage

WNT7B

Protein Wnt-7b · UniProt P56706

Length
349 aa
Mass
39.3 kDa
Annotated
2026-06-11
100 papers in source corpus 36 papers cited in narrative 37 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

WNT7B is a secreted Wnt ligand that coordinates proliferation, differentiation, and morphogenesis across developing and regenerating tissues by activating both canonical (β-catenin) and non-canonical Wnt responses in adjacent or autocrine target cells (PMID:15923619, PMID:18367557). It binds Frizzled receptors at the cell surface—Frizzled-1 and -10 in cooperation with the LRP5 co-receptor to drive canonical signaling (PMID:15923619), and Frizzled-7, -4, or -5 in other contexts (PMID:29898920, PMID:39301638, PMID:34562599)—and in CNS, retinal, and limb vasculature WNT7-specific signaling additionally requires the membrane co-activator complex of RECK and the orphan GPCR GPR124, which assemble with Frizzled into a multiprotein receptor unit (PMID:28803732, PMID:35552394, PMID:30478038). A recurring theme is paracrine action: macrophage- or myeloid-derived WNT7B activates canonical Wnt responses in neighboring endothelial and epithelial cells to drive hyaloid vessel regression, kidney repair, and tumor angiogenesis through induction of VEGFA (PMID:16163358, PMID:20160075, PMID:24638982), while epithelium-derived WNT7B instructs mesenchymal and mural-cell behavior during lung, kidney, and placental development (PMID:12361974, PMID:19060336, PMID:11543617, PMID:27432740). In bone, WNT7B promotes osteoblast activity through PI3K-AKT-driven mTORC1 activation and GLUT1-dependent glycolysis (PMID:24497849, PMID:30913395), and through β-catenin-independent Ca2+/NFATc1-SOX11 signaling (PMID:32346881). Non-canonical outputs—JNK, CaMKII, PKC, and ERK1/2—mediate neuronal dendritic arborization, neurite outgrowth, and odontoblast differentiation (PMID:29898920, PMID:18177422, PMID:33125912, PMID:31181411). WNT7B transcription is set by tissue-restricted factors (TTF-1/GATA6/Foxa2 in lung) and by BMP and androgen-receptor signaling, and is repressed epigenetically by LSD1 and by the G9a-recruiting lncRNA Lnc-Rewind (PMID:11914369, PMID:24222445, PMID:23386686, PMID:29707403, PMID:33432928). Bi-allelic loss-of-function variants in WNT7B cause PDAC syndrome (pulmonary hypoplasia, diaphragmatic anomalies, anophthalmia/microphthalmia, cardiac and genitourinary defects), with variant deleteriousness validated by canonical WNT signaling reporter assays (PMID:35790350).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2002 High

    Establishing how WNT7B transcription is restricted to specific epithelia answered which upstream regulators license its expression, and identified epithelial WNT7B as an essential paracrine signal for mesenchymal development.

    Evidence EMSA, reporter, Co-IP, and promoter mutagenesis defining TTF-1/GATA6/Foxa2 regulation; germline lacZ knockout showing lung hypoplasia and pulmonary vascular smooth-muscle defects

    PMID:11914369 PMID:12361974

    Open questions at the time
    • Did not resolve the receptor on responding mesenchymal cells
    • Transcriptional control characterized only in lung context
  2. 2005 High

    Identifying the receptor partners answered whether WNT7B is intrinsically canonical, showing it binds Frizzled-1/-10 with LRP5 to activate β-catenin and, in macrophages, acts as a short-range paracrine signal driving endothelial apoptosis.

    Evidence Cell-surface binding and canonical-vs-noncanonical reporter assays; macrophage-specific conditional Wnt7b deletion in mouse eye

    PMID:15923619 PMID:16163358

    Open questions at the time
    • Pathway choice shown to be cell-type dependent, not explained at the molecular level
    • Receptor identity in macrophage-endothelial paracrine signaling not directly mapped
  3. 2009 High

    Genetic epistasis with β-catenin established that epithelial WNT7B controls mesenchymal/interstitial cell-division plane orientation, defining its role in organ axis formation beyond simple proliferation.

    Evidence Conditional Wnt7b and interstitial β-catenin knockouts with division-plane and urine-concentration analysis in kidney

    PMID:18367557 PMID:19060336

    Open questions at the time
    • Effector genes downstream of β-catenin in oriented division not identified
    • Autocrine vs paracrine contributions only partially separated
  4. 2013 Medium

    Cancer and vascular studies answered whether WNT7B acts autocrine or paracrine in disease, showing autocrine β-catenin signaling sustains PDAC growth while AR-driven WNT7B uses non-canonical PKC, and EC-intrinsic WNT7B suppresses endothelial-mesenchymal transition.

    Evidence siRNA/WLS/IWP-2 reporter assays in PDAC; AR ChIP and PKC inhibitors in CRPC; endothelial-specific Cdh5-Cre knockout with osteogenic-gene and Smad1/5 analysis

    PMID:23386686 PMID:23416978 PMID:23685555

    Open questions at the time
    • Receptors mediating autocrine signaling in these contexts not defined
    • PKC isozyme specificity not fully resolved
  5. 2014 High

    Bone and tumor-angiogenesis work answered how WNT7B couples to metabolism and the angiogenic switch, placing PI3K-AKT-mTORC1 downstream in osteoblasts and VEGFA induction downstream in tumor endothelium.

    Evidence Raptor-deletion epistasis rescuing WNT7B high-bone-mass phenotype; myeloid-specific Wnt7b knockout in MMTV-PyMT with VEC reporter and VEGFA analysis

    PMID:24497849 PMID:24638982

    Open questions at the time
    • How a Wnt ligand engages PI3K-AKT mechanistically not resolved
    • Link between canonical signaling and VEGFA transcription not directly mapped
  6. 2017 High

    Discovery of the RECK-GPR124 co-activator complex answered how WNT7B achieves ligand-specific signaling in CNS endothelium, defining a multiprotein receptor unit assembled with Frizzled.

    Evidence EC-specific Reck knockouts, interface mutagenesis, and soluble-domain probe binding assays demonstrating Frizzled-WNT7-RECK-GPR124 assembly

    PMID:28803732

    Open questions at the time
    • Stoichiometry and structure of the assembled complex not solved
    • How RECK/GPR124 bias signaling output not defined
  7. 2018 High

    Neuronal and barrier studies answered which non-canonical effectors WNT7B uses and how it cooperates with related ligands, identifying Frizzled-7/Dvl1-CaMKII/JNK signaling for dendrites and partial redundancy with Norrin for the blood-brain/retina barrier.

    Evidence Fz7 loss-of-function with CaMKII/JNK phospho-readouts in hippocampus; combinatorial Wnt7a/Wnt7b/Norrin/Frizzled4 conditional knockouts with BBB/BRB phenotyping

    PMID:18177422 PMID:29898920 PMID:30478038

    Open questions at the time
    • Functional separation of WNT7A vs WNT7B contributions limited
    • Connection between CaMKII/JNK activation and cytoskeletal remodeling not detailed
  8. 2021 Medium

    Epigenetic and stem-cell studies answered how WNT7B levels are tuned and how it signals β-catenin-independently, defining LSD1 and Lnc-Rewind/G9a-H3K9 repression and a Ca2+/NFATc1-SOX11 osteogenic axis.

    Evidence LSD1 conditional knockout with WNT7B epistasis; RIP/ChIP for G9a-H3K9me2 at the Wnt7b locus; transgenic overexpression with ChIP-qPCR for NFATc1-SOX11 targets

    PMID:29707403 PMID:32346881 PMID:33432928

    Open questions at the time
    • Epigenetic regulators tested in single lineages only
    • Receptor coupling to the Ca2+/NFATc1 branch not identified
  9. 2022 Medium

    Human genetics and limb genetics answered whether WNT7B loss is disease-causing and whether the RECK-GPR124 unit operates outside CNS, defining PDAC syndrome and a WNT7-FZD-LRP5/6-GPR124-RECK module in limb skeletal growth.

    Evidence Exome sequencing with canonical WNT luciferase validation and zebrafish ortholog; combinatorial Wnt7a/Wnt7b/Gpr124/Reck alleles with a signaling-specific Reck allele in limb

    PMID:35552394 PMID:35790350

    Open questions at the time
    • Genotype-phenotype correlation across PDAC variants incompletely defined
    • Tissue-specific deployment of the RECK-GPR124 module not comprehensively mapped
  10. 2024 Medium

    Cochlear and additional disease studies answered how WNT7B drives planar cell polarity and clarified receptor usage, defining a Wnt5a/Wnt7b-Daple-Gαi-PI3K/AKT/ERK PCP pathway and FZD4/FZD5 receptor contexts.

    Evidence Wnt5a/Wnt7b double knockout with Daple recruitment, PI3K/AKT/ERK and Fzd6 localization analysis; FZD4 Co-IP/rescue and FZD5-ELF3-NOTCH1 axis studies; founder-variant reporter assay

    PMID:34562599 PMID:38417950 PMID:39172791 PMID:39301638

    Open questions at the time
    • Multiple Frizzled receptors implicated without a unifying selectivity rule
    • Whether the same Daple/PCP machinery operates in other WNT7B-dependent tissues unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved what determines WNT7B's choice between canonical and non-canonical outputs across tissues, and how its diverse Frizzled receptors and the RECK-GPR124 co-activator are selected in each context.
  • No structural model of WNT7B-receptor-coreceptor complexes
  • Rules governing canonical vs non-canonical pathway selection unknown
  • Receptor-effector matching across tissues not systematically mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0060089 molecular transducer activity 3
Localization
GO:0005576 extracellular region 3
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3
Partners
FZD1FZD10FZD4FZD5FZD7GPR124LRP5RECK
Complex memberships
WNT7-Frizzled-LRP5/6-GPR124-RECK signaling complex

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 WNT7B activates canonical (β-catenin) Wnt signaling by binding to Frizzled-1 (Fzd1) and Frizzled-10 (Fzd10) on the cell surface, and cooperatively activates canonical Wnt signaling with these receptors in the presence of LRP5 co-receptor; it does not activate the noncanonical Wnt pathway in these cell types. Cell transfection assays, biochemical cell-surface binding studies, canonical vs. non-canonical Wnt pathway reporter assays Molecular and Cellular Biology High 15923619
2005 Macrophage-derived WNT7B acts as a short-range paracrine signal that activates the canonical WNT pathway in vascular endothelial cells of hyaloid vessels, triggering programmed cell death (apoptosis) and vessel regression during eye development. Conditional genetic deletion of Wnt7b in macrophages in mice, analysis of canonical WNT pathway responses and apoptosis in hyaloid vessel endothelial cells Nature High 16163358
2010 Macrophage-derived WNT7B stimulates canonical Wnt pathway responses in kidney epithelial cells to promote tissue repair and regeneration after injury; inducible ablation of macrophages reduces canonical Wnt pathway activity in kidney epithelium, and somatic deletion of Wnt7b in macrophages greatly diminishes kidney repair. Inducible macrophage ablation, conditional somatic deletion of Wnt7b in macrophages, canonical Wnt pathway reporter analysis in kidney epithelial cells Proceedings of the National Academy of Sciences of the United States of America High 20160075
2002 Wnt7b expressed in airway epithelium is required for mesenchymal proliferation and vascular smooth muscle development in the lung; germline deletion causes lung hypoplasia and defects in smooth muscle of major pulmonary vessels leading to hemorrhage. Germline knockout mouse (replacement of first exon with lacZ), histological and phenotypic analysis Development (Cambridge, England) High 12361974
2009 Wnt7b expressed in collecting duct epithelium regulates the orientation of epithelial cell division planes (longitudinal vs. radial axis) via paracrine canonical Wnt signaling through β-catenin in the underlying interstitium, thereby establishing the cortico-medullary axis and enabling urine concentration; removal of β-catenin from Wnt-responsive interstitium phenocopies the Wnt7b mutant medullary defect. Conditional Wnt7b knockout, β-catenin conditional knockout in interstitium, analysis of cell division plane orientation, urine concentration assays, genetic epistasis Development (Cambridge, England) High 19060336
2008 Conditional Wnt7b-null lungs are hypoplastic due to decreased replication of both epithelium and mesenchyme; Wnt7b activates both autocrine and paracrine canonical Wnt signaling cascades and modulates multiple downstream signaling pathways to coordinate proliferation of adjacent cell types. Conditional Wnt7b knockout mouse, BrdU/proliferation assays, canonical Wnt pathway analysis in epithelium and mesenchyme Development (Cambridge, England) High 18367557
2001 Wnt7b expression in the chorion is required for chorion-allantois fusion during placental development; in Wnt7b mutant mice, α4 integrin protein (required for chorioallantoic fusion) is not expressed by cells in the mutant chorion. Targeted germline mutation of mouse Wnt7b, immunohistochemistry for α4 integrin, histological analysis Developmental Biology High 11543617
2002 WNT7B promoter is directly regulated by the lung-restricted transcription factors TTF-1, GATA6, and Foxa2; TTF-1 and GATA6 physically interact in vivo and synergistically activate the WNT7B promoter, and GATA6/Foxa2 binding site truncations reduce trans-activation. Electrophoretic mobility shift assays (EMSA), cotransfection reporter assays, promoter truncation analysis, co-immunoprecipitation (TTF-1/GATA6 interaction) The Journal of Biological Chemistry High 11914369
2014 WNT7B promotes bone formation by activating mTORC1 through the PI3K-AKT signaling pathway; genetic disruption of mTORC1 (by deleting Raptor in the osteoblast lineage) alleviates the WNT7B-induced high-bone-mass phenotype, establishing mTORC1 as a required downstream effector. Conditional transgenic overexpression of WNT7B in osteoblasts, conditional knockout of Raptor in osteoblasts, bone mass analysis, pathway activity assays PLoS Genetics High 24497849
2017 Reck (GPI-anchored membrane protein) and Gpr124 (orphan GPCR) function as essential receptor cofactors for WNT7A/WNT7B-specific signaling in CNS vascular endothelial cells; the most N-terminal domain of Reck binds to the LRR and Ig domains of Gpr124; soluble Gpr124(LRR-Ig) probe binds to cells expressing Frizzled, WNT7A or WNT7B, and Reck; soluble Reck(CC1-5) probe binds to cells expressing Frizzled, WNT7A or WNT7B, and Gpr124, indicating a multiprotein complex. EC-specific conditional knockouts of Reck, targeted mutagenesis of Reck-Gpr124 interface, soluble probe binding assays, CNS angiogenesis and BBB phenotype analysis Neuron High 28803732
2014 Myeloid cell-derived WNT7B mediates the angiogenic switch in breast cancer by activating Wnt/β-catenin signaling specifically in vascular endothelial cells (VECs), increasing VEGFA mRNA and protein expression in VECs; myeloid-specific Wnt7b deletion reduces VEC Wnt/β-catenin target gene expression, reduces tumor-associated VEGFA, impairs angiogenesis, and diminishes macrophage-mediated tumor cell invasion and lung metastasis. Myeloid-specific conditional Wnt7b knockout in MMTV-PymT breast cancer model, Wnt/β-catenin pathway reporter analysis in VECs, VEGFA expression analysis, tumor angiogenesis and metastasis assays Cancer Research High 24638982
2018 Wnt7b signals through the Frizzled-7 (Fz7) receptor in hippocampal neurons to promote dendritic arborization via a non-canonical Wnt pathway; Fz7 loss-of-function impairs dendritic growth both in vitro and in vivo in the mouse hippocampus; Wnt7b-Fz7 signaling induces phosphorylation of CaMKII and JNK, both required for dendritic development. Fz7 loss-of-function (shRNA and dominant-negative), in vivo dendritic analysis in mouse hippocampus, Western blot for CaMKII and JNK phosphorylation, pharmacological inhibition Journal of Cell Science High 29898920
2013 WNT7B drives autocrine Wnt/β-catenin signaling in pancreatic adenocarcinoma (PDAC) cells; WNT7B knockdown reduces Wnt/β-catenin transcriptional activity and anchorage-independent growth, and WLS silencing or IWP-2 (which blocks Wnt ligand processing/secretion) also inhibits Wnt/β-catenin activity, placing WNT7B upstream as the primary ligand. siRNA knockdown of WNT7B in PDAC cell lines, WLS silencing, IWP-2 treatment, Wnt/β-catenin luciferase reporter assay, anchorage-independent growth assay Oncogene High 23416978
2013 WNT7B is a direct androgen receptor (AR) target gene in castration-resistant prostate cancer (CRPC); WNT7B promotes androgen-independent growth of CRPC cells through activation of protein kinase C (PKC) isozymes (non-canonical Wnt pathway); WNT7B produced by prostate cancer cells induces osteoblast differentiation through direct cell-cell interaction. AR chromatin immunoprecipitation, WNT7B knockdown in CRPC cells, PKC pathway inhibitors, osteoblast co-culture differentiation assays Molecular Cancer Research Medium 23386686
2013 Dkk1 (a Wnt antagonist) inhibits Wnt7b-induced canonical Wnt signaling in kidney collecting duct cells; Dkk1 deficiency in the developing kidney leads to increased expression of canonical Wnt target Lef-1 in stromal cells, and Dkk1 regulates the degree of Wnt7b signaling during kidney papilla development. Recombinant Dkk1 protein treatment of cultured cells with Wnt7b stimulation, conditional Dkk1 knockout mouse, Lef-1 expression analysis Developmental Biology Medium 21354128
2013 In aortic endothelial cells, Wnt7b and Msx2 preserve endothelial cell phenotype and maintain expression of EC differentiation markers; endothelial cell-specific deletion of Wnt7b (using Cdh5-Cre) in Wnt7b(fl/fl);LDLR(-/-) mice upregulates aortic osteogenic genes (Osx, Sox9, Runx2, Msx2) and activates Smad1/5 phosphorylation, indicating that EC Wnt7b suppresses endothelial-mesenchymal transition. Endothelial-specific conditional Wnt7b knockout (Cdh5-Cre), adenoviral Dkk1/Wnt7b/Msx2 overexpression in primary aortic ECs, Western blot, gene expression analysis Arteriosclerosis, Thrombosis, and Vascular Biology High 23685555
2019 Wnt7b promotes bone formation through stimulation of glucose metabolism (glycolysis) in osteoblast lineage cells; Wnt7b increases GLUT1 expression and glucose consumption, and genetic deletion of GLUT1 (Glut1) essentially abolishes Wnt7b-induced bone formation in vivo, demonstrating GLUT1-dependent glycolysis as a required downstream mechanism. Compound transgenic mice overexpressing Wnt7b with conditional Glut1 deletion, in vivo bone formation assays (μCT), primary osteoblast culture differentiation, glucose consumption assays FASEB Journal High 30913395
2018 Wnt7b acts through Frizzled-7 (Fz7) and the scaffold protein Dvl1 to modulate dendrite arborisation via non-canonical Wnt signaling in hippocampal neurons (β-catenin-independent pathway). Loss-of-function (Fz7 knockdown), in vitro and in vivo dendritic arborization analysis, reference to Dvl1 scaffold role Journal of Cell Science Medium 29898920
2008 Wnt7b is a p53 transcriptional target gene in PC12 neuronal cells; NGF signaling stabilizes p53, which induces wnt7b expression in a p53-dependent manner; secreted Wnt7b promotes neurite outgrowth through non-canonical JNK signaling (not β-catenin nuclear translocation); sFRP1 inhibits wnt7b-dependent JNK phosphorylation, confirming that Wnt7b is secreted and acts extracellularly. Stable shRNA-mediated p53 silencing, wnt7b overexpression rescue of neurite outgrowth in p53-silenced cells, JNK inhibitor (SP600125), sFRP1 treatment, β-catenin nuclear localization assay Differentiation Medium 18177422
2014 In hair follicle stem cells (hfSCs), Wnt7b is a direct transcriptional target of canonical BMP signaling; conditional Wnt7b gene targeting disrupts hair follicle cycling (shorter anagen, premature catagen), diminishes HF differentiation markers, and delays HF activation, demonstrating a non-redundant role for Wnt7b in anagen length and catagen entry. Conditional Wnt7b knockout (morphogenesis and postnatal), BMP signaling manipulation, flow cytometry, BrdU labeling, marker expression analysis Stem Cells High 24222445
2021 The lncRNA Lnc-Rewind acts as an epigenetic regulator that represses Wnt7b expression in muscle stem cells (MuSCs) in cis; Lnc-Rewind interacts with the G9a histone lysine methyltransferase and mediates repression of Wnt7b by H3K9me2 deposition at the Wnt7b locus. RNA immunoprecipitation (RIP) for G9a interaction, ChIP for H3K9me2 at Wnt7b locus, lncRNA loss-of-function, RNA-seq in MuSCs eLife Medium 33432928
2018 The histone demethylase LSD1 (KDM1A) epigenetically represses WNT7B expression in osteoblasts; LSD1 deficiency results in increased WNT7B expression, enhanced osteoblast differentiation, and increased bone mass; genetic downregulation of WNT7B-related signaling attenuates the bone phenotype in LSD1-deficient mice. LSD1 knockdown in human MSCs, conditional LSD1 knockout mice, WNT7B expression analysis, genetic inhibition of WNT7B signaling, small-molecule inhibitor studies Bone Research Medium 29707403
2016 Wnt7b expressed in ureteric bud epithelium activates canonical Wnt signaling in mural cells of periureteric bud capillaries in the renal medulla; Wnt7b loss enhances proliferation of target mural cells (associated with decreased PDGFRβ and p57kip2 expression) and impairs capillary lumen formation by reducing VE-cadherin at the cell surface of medullary capillary endothelium. Conditional Wnt7b knockout, immunofluorescence for mural cell markers, VE-cadherin localization analysis, proliferation assays Journal of the American Society of Nephrology Medium 27432740
2022 EZH2 interacts with HP1BP3 in glioma stem cells, impairing H3K9 methylation, and this EZH2-HP1BP3 complex co-activates WNT7B expression; autocrine WNT7B/β-catenin signaling promotes TMZ resistance and stemness in GBM, and WNT7B inhibition (LGK974) reverses TMZ resistance. Co-immunoprecipitation plus mass spectrometry, ChIP, WNT7B overexpression/knockdown, LGK974 WNT secretion inhibitor, TMZ resistance assays, glioma stem cell self-renewal assays Oncogene Medium 36517590
2020 Wnt7b-induced Sox11 expression in bone marrow mesenchymal stem cells (BMSCs) enhances self-renewal and osteogenic differentiation; this signaling is β-catenin-independent and instead activates Ca2+-dependent Nfatc1 signaling to directly induce Sox11 transcription; Sox11 in turn activates transcription of proliferation-related (Ccnb1, Sox2) and osteogenesis-related (Runx2, Sp7) factors. Transgenic mouse overexpression, RNA-seq, ChIP-qPCR (Sox11 binding to target promoters), shRNA knockdown, colony formation and osteogenic differentiation assays, Nfatc1 pathway analysis Stem Cells Medium 32346881
2017 WNT7B promotes migration and differentiation (odontogenic/osteogenic) of human dental pulp cells partly through activation of both the canonical WNT/β-catenin pathway and the non-canonical JNK pathway; pharmacological inhibition of either pathway (XAV939 or SP600125) partly offsets WNT7B-induced differentiation. Recombinant WNT7B protein treatment, WNT/β-catenin luciferase reporter, Western blot for pathway activation, pathway inhibitors (XAV939, SP600125), ALP activity, alizarin red staining, scratch assay Archives of Oral Biology Medium 29268145
2024 Wnt7b acts as a non-canonical Wnt (ncWnt) ligand in concert with Wnt5a to regulate cochlear duct elongation and planar cell polarity; Wnt5a/Wnt7b are redundantly required for cochlear morphogenesis; mechanistically, Wnt5a/Wnt7b-mediated ncWnt signaling promotes membrane recruitment of Daple (a Gαi guanine nucleotide exchange factor) and activates PI3K/AKT and ERK signaling to regulate asymmetric Fzd6 localization. Conditional/conventional loss-of-function mouse genetics (Wnt5a/Wnt7b double KO), PI3K/AKT and ERK pathway analysis, PCP protein localization (Fzd6, Dvl2), Daple membrane recruitment assay Proceedings of the National Academy of Sciences of the United States of America High 39172791
2022 The WNT7A/WNT7B-FRIZZLED-LRP5/LRP6-GPR124-RECK signaling system functions as an integral unit in limb development; loss-of-function alleles for Wnt7a, Wnt7b, Gpr124, and Reck synergize to cause reduced and dysmorphic limb bone growth, and a Reck allele specifically defective in WNT7A/WNT7B signaling recapitulates limb phenotypes. Combinations of conventional and conditional loss-of-function alleles for Wnt7a, Wnt7b, Gpr124, Reck in mice; Reck structure-function allele specifically defective in WNT7A/WNT7B signaling; limb bone growth and patterning analysis Development (Cambridge, England) High 35552394
2021 WNT7B/FZD5 signaling activates a pathway involving ELF3 transcription factor, which in turn transcriptionally modulates NOTCH1, functioning as a tumor-suppressing axis in bladder urothelial carcinoma that represses EMT, stem-like properties, and chemoresistance. Loss-of-function and gain-of-function studies in bladder cancer cell lines, receptor identification (FZD5 as WNT7B receptor), downstream ELF3/NOTCH1 pathway analysis, EMT and stemness marker assays Biochimica et Biophysica Acta – Molecular Basis of Disease Medium 34562599
2015 In human pancreatic progenitor cells (PPCs), WNT7B (and Wnt7a) specifically promotes progenitor cell proliferation through the non-canonical Wnt/PKC pathway, not the canonical Wnt pathway; YY1 functions as a transcriptional regulator of WNT7B expression in PPCs. siRNA screening, feeder cell lines stably expressing individual Wnt ligands, canonical vs. non-canonical Wnt pathway reporters, phosphoproteome analysis, YY1 transcriptional regulator identification Cell Chemical Biology Medium 33125912
2019 Wnt7b promotes dentinogenesis by increasing proliferation and differentiation of dental mesenchymal cells partly through the ERK1/2 pathway; transgenic mice overexpressing Wnt7b in odontoblasts show increased p-ERK1/2, thinner predentin, and thicker intertubular dentin with higher mineral content; ERK1/2 inhibition partly rescues Wnt7b-induced differentiation. Dmp1-cre;ROSA26-Wnt7b transgenic mice, adenoviral Wnt7b overexpression in dental papillae cells, ERK1/2 inhibitor, Western blot, micro-CT, ALP/alizarin red staining Archives of Oral Biology Medium 31181411
2022 Bi-allelic loss-of-function variants in WNT7B cause PDAC syndrome (pulmonary hypoplasia, diaphragmatic anomalies, anophthalmia/microphthalmia, cardiac defects); functional validation using a canonical WNT signaling luciferase assay demonstrated that identified WNT7B variants (p.Arg98*, p.Tyr75*, p.Gly188Ser) are deleterious to WNT7B signaling activity. Whole-exome sequencing, canonical WNT signaling luciferase reporter assay for variant functional validation, wnt7bb mutant zebrafish (swimbladder phenotype) Journal of Medical Genetics Medium 35790350
2023 Wnt7b expressed by hypertrophic chondrocytes promotes endochondral ossification; Wnt7b expression in growth plate cartilage is suppressed by BMP4/Smad4 signaling; ablation of Wnt7b in Smad4 cKO mice blunts the increased bone volume phenotype, establishing Wnt7b-β-catenin as a downstream effector of Smad4-BMP signaling during endochondral ossification. Conditional Smad4 knockout, conditional Wnt7b knockout in Smad4 cKO background (genetic epistasis), BMP4 stimulation in chondrocytes, bone volume analysis Development (Cambridge, England) Medium 37539462
2024 WNT7B binds to FZD4 (frizzled-4) receptor in periodontal ligament stem cells; Wnt7b overexpression promotes osteogenic differentiation and suppresses M1 macrophage polarization; FZD4 silencing reverses these effects, placing FZD4 as the receptor mediating WNT7B function in this context. Co-immunoprecipitation (WNT7B-FZD4 binding), FZD4 siRNA rescue experiments, osteogenic differentiation assays, macrophage polarization assays, Western blot Molecular Medicine Reports Medium 39301638
2021 WNT7B in cholangiocytes induces a proproliferative, proinflammatory program: in vitro, Wnt7b induces cholangiocyte proliferation and secretion of proinflammatory cytokines in an autocrine manner; loss of cholangiocyte/hepatocyte Wnt7b in vivo improves biliary injury and decreases cellular senescence in cholestasis, and Wnt7b suppression promotes hepatocyte reprogramming toward a biliary phenotype. Conditional Wnt7b knockout (Krt19-Cre and Albumin-Cre), DDC cholestasis model, proliferation assays, cytokine secretion assays, senescence markers, hepatocyte reprogramming markers Hepatology Communications Medium 34558852
2018 In the context of partially impaired Norrin signaling, the Wnt7a/Wnt7b system makes a contribution to blood-retina barrier (BRB) development; combined loss of Wnt7a and Norrin or Wnt7a and Frizzled4 causes far more severe BBB defects than loss of any single component, demonstrating partial redundancy between the Wnt7a/Wnt7b and Norrin signaling systems in BBB/BRB maintenance. Compound conditional knockouts (Wnt7a, Wnt7b, Norrin, Frizzled4, Tspan12) in mice, BBB/BRB phenotype analysis, glial-specific Wnt7a deletion Proceedings of the National Academy of Sciences of the United States of America High 30478038
2024 A founder WNT7B variant (Arg247Trp) significantly impairs WNT7B canonical signaling activity as demonstrated by luciferase reporter assay, causing variable PDAC syndrome phenotypes including isolated genitourinary anomalies, expanding the known phenotypic spectrum. Canonical WNT signaling luciferase reporter assay for variant functional validation Clinical Genetics Low 38417950

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Macrophage Wnt7b is critical for kidney repair and regeneration. Proceedings of the National Academy of Sciences of the United States of America 365 20160075
2005 WNT7b mediates macrophage-induced programmed cell death in patterning of the vasculature. Nature 355 16163358
2002 Wnt7b regulates mesenchymal proliferation and vascular development in the lung. Development (Cambridge, England) 276 12361974
2009 A Wnt7b-dependent pathway regulates the orientation of epithelial cell division and establishes the cortico-medullary axis of the mammalian kidney. Development (Cambridge, England) 189 19060336
2017 Reck and Gpr124 Are Essential Receptor Cofactors for Wnt7a/Wnt7b-Specific Signaling in Mammalian CNS Angiogenesis and Blood-Brain Barrier Regulation. Neuron 161 28803732
2005 Wnt7b activates canonical signaling in epithelial and vascular smooth muscle cells through interactions with Fzd1, Fzd10, and LRP5. Molecular and cellular biology 159 15923619
2014 Myeloid WNT7b mediates the angiogenic switch and metastasis in breast cancer. Cancer research 154 24638982
2018 Interplay of the Norrin and Wnt7a/Wnt7b signaling systems in blood-brain barrier and blood-retina barrier development and maintenance. Proceedings of the National Academy of Sciences of the United States of America 133 30478038
2008 Wnt7b stimulates embryonic lung growth by coordinately increasing the replication of epithelium and mesenchyme. Development (Cambridge, England) 133 18367557
2001 Wnt7b regulates placental development in mice. Developmental biology 124 11543617
2014 WNT7B promotes bone formation in part through mTORC1. PLoS genetics 121 24497849
2014 Downregulated miR329 and miR410 promote the proliferation and invasion of oral squamous cell carcinoma by targeting Wnt-7b. Cancer research 119 25351956
2013 WNT7B mediates autocrine Wnt/β-catenin signaling and anchorage-independent growth in pancreatic adenocarcinoma. Oncogene 108 23416978
2001 Pax-6 regulates expression of SFRP-2 and Wnt-7b in the developing CNS. The Journal of neuroscience : the official journal of the Society for Neuroscience 106 11222670
2001 Molecular cloning and characterization of human WNT7B. International journal of oncology 103 11562755
2013 Dkk1 and MSX2-Wnt7b signaling reciprocally regulate the endothelial-mesenchymal transition in aortic endothelial cells. Arteriosclerosis, thrombosis, and vascular biology 97 23685555
2002 The WNT7b promoter is regulated by TTF-1, GATA6, and Foxa2 in lung epithelium. The Journal of biological chemistry 96 11914369
2015 Identification of myopia-associated WNT7B polymorphisms provides insights into the mechanism underlying the development of myopia. Nature communications 77 25823570
2014 Wnt7b is an important intrinsic regulator of hair follicle stem cell homeostasis and hair follicle cycling. Stem cells (Dayton, Ohio) 76 24222445
2002 Expression of WNT7A in human normal tissues and cancer, and regulation of WNT7A and WNT7B in human cancer. International journal of oncology 75 12239632
2015 Expression of WNT5A in Idiopathic Pulmonary Fibrosis and Its Control by TGF-β and WNT7B in Human Lung Fibroblasts. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 69 26538547
2013 Role of WNT7B-induced noncanonical pathway in advanced prostate cancer. Molecular cancer research : MCR 58 23386686
2002 Expression patterns of Wnt8b and Wnt7b in the chicken embryonic brain suggest a correlation with forebrain patterning centers and morphogenesis. Neuroscience 58 12150789
2019 Increased glycolysis mediates Wnt7b-induced bone formation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 53 30913395
2019 circ_0001730 promotes proliferation and invasion via the miR-326/Wnt7B axis in glioma cells. Epigenomics 47 31304776
2019 Long noncoding RNA OIP5-AS1 targets Wnt-7b to affect glioma progression via modulation of miR-410. Bioscience reports 46 30498093
2015 Wnt7b is required for epithelial progenitor growth and operates during epithelial-to-mesenchymal signaling in pancreatic development. Developmental biology 46 25576928
2018 Histone demethylase LSD1 regulates bone mass by controlling WNT7B and BMP2 signaling in osteoblasts. Bone research 45 29707403
2020 Inducible expression of Wnt7b promotes bone formation in aged mice and enhances fracture healing. Bone research 44 32047703
2011 Secreted Wnt antagonist Dickkopf-1 controls kidney papilla development coordinated by Wnt-7b signalling. Developmental biology 44 21354128
2020 Wnt7b-induced Sox11 functions enhance self-renewal and osteogenic commitment of bone marrow mesenchymal stem cells. Stem cells (Dayton, Ohio) 41 32346881
2019 miR-342-5p inhibits osteosarcoma cell growth, migration, invasion, and sensitivity to Doxorubicin through targeting Wnt7b. Cell cycle (Georgetown, Tex.) 36 31601147
2019 LncRNA TMPO-AS1 serves as a ceRNA to promote osteosarcoma tumorigenesis by regulating miR-199a-5p/WNT7B axis. Journal of cellular biochemistry 36 31680323
2020 Extracellular vesicular Wnt7b mediates HPV E6-induced cervical cancer angiogenesis by activating the β-catenin signaling pathway. Journal of experimental & clinical cancer research : CR 35 33234148
2019 Klotho/FGF23 axis mediates high phosphate-induced vascular calcification in vascular smooth muscle cells via Wnt7b/β-catenin pathway. The Kaohsiung journal of medical sciences 32 31001900
2000 Retroviral expression of Wnt-1 and Wnt-7b produces different effects in mouse mammary epithelium. Journal of cell science 31 10825286
2018 Wnt7b signalling through Frizzled-7 receptor promotes dendrite development by coactivating CaMKII and JNK. Journal of cell science 29 29898920
2018 Combination with TMZ and miR-505 inhibits the development of glioblastoma by regulating the WNT7B/Wnt/β-catenin signaling pathway. Gene 27 29906532
2007 Human chorionic gonadotropin (hCG) up-regulates wnt5b and wnt7b in the mammary gland, and hCGbeta transgenic female mice present with mammary Gland tumors exhibiting characteristics of the Wnt/beta-catenin pathway activation. Endocrinology 27 17510243
2023 LncRNA OIP5-AS1/miR-410-3p/Wnt7b axis promotes the proliferation of rheumatoid arthritis fibroblast-like synoviocytes via regulating the Wnt/β-catenin pathway. Autoimmunity 26 36942896
2021 Epigenetic regulation of Wnt7b expression by the cis-acting long noncoding RNA Lnc-Rewind in muscle stem cells. eLife 26 33432928
2021 Fzd7/Wnt7b signaling contributes to stemness and chemoresistance in pancreatic cancer. Cancer medicine 26 33934523
2014 Wnt7b can replace Ihh to induce hypertrophic cartilage vascularization but not osteoblast differentiation during endochondral bone development. Bone research 24 26273517
2022 Canonical WNT Signaling Activated by WNT7B Contributes to L-HBs-Mediated Sorafenib Resistance in Hepatocellular Carcinoma by Inhibiting Mitophagy. Cancers 22 36497264
2022 EZH2 interacts with HP1BP3 to epigenetically activate WNT7B that promotes temozolomide resistance in glioblastoma. Oncogene 22 36517590
1998 High expression of Wnt7b in human superficial bladder cancer vs invasive bladder cancer. British journal of cancer 22 9461004
2023 α7nAChR activation in AT2 cells promotes alveolar regeneration through WNT7B signaling in acute lung injury. JCI insight 20 37410546
2016 An electrochemical biosensor for double-stranded Wnt7B gene detection based on enzymatic isothermal amplification. Biosensors & bioelectronics 20 27326913
2017 The WNT7B protein promotes the migration and differentiation of human dental pulp cells partly through WNT/beta-catenin and c-Jun N-terminal kinase signalling pathways. Archives of oral biology 17 29268145
2016 Wnt7b Signaling from the Ureteric Bud Epithelium Regulates Medullary Capillary Development. Journal of the American Society of Nephrology : JASN 17 27432740
2021 The Role of miR-640: A Potential Suppressor in Breast Cancer via Wnt7b/β-catenin Signaling Pathway. Frontiers in oncology 16 33912460
2021 WNT7B represses epithelial-mesenchymal transition and stem-like properties in bladder urothelial carcinoma. Biochimica et biophysica acta. Molecular basis of disease 16 34562599
2008 The p53 transcriptional target gene wnt7b contributes to NGF-inducible neurite outgrowth in neuronal PC12 cells. Differentiation; research in biological diversity 16 18177422
2023 LncRNA MALAT1 mediates osteogenic differentiation in osteoporosis by regulating the miR-485-5p/WNT7B axis. Frontiers in endocrinology 15 36760811
2022 The WNT7A/WNT7B/GPR124/RECK signaling module plays an essential role in mammalian limb development. Development (Cambridge, England) 15 35552394
2020 Knockdown of LINC00657 inhibits ox-LDL-induced endothelial cell injury by regulating miR-30c-5p/Wnt7b/β-catenin. Molecular and cellular biochemistry 15 32577947
2021 WNT7B Regulates Cholangiocyte Proliferation and Function During Murine Cholestasis. Hepatology communications 14 34558852
2020 Combined Omics Approaches Reveal the Roles of Non-canonical WNT7B Signaling and YY1 in the Proliferation of Human Pancreatic Progenitor Cells. Cell chemical biology 14 33125912
2022 Total Saponins of Radix Clematis Regulate Fibroblast-Like Synoviocyte Proliferation in Rheumatoid Arthritis via the LncRNA OIP5-AS1/MiR-410-3p/Wnt7b Signaling Pathway. Evidence-based complementary and alternative medicine : eCAM 12 35668775
2022 miR-342-5p inhibits odonto/osteogenic differentiation of human dental pulp stem cells via targeting Wnt7b. Oral diseases 10 35322903
2021 WNT7B overexpression rescues bone loss caused by glucocorticoids in mice. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 10 34118078
2014 Transgenic increase of Wnt7b in neural progenitor cells decreases expression of T-domain transcription factors and impairs neuronal differentiation. Brain research 10 24953933
2024 Wnt7b acts in concert with Wnt5a to regulate tissue elongation and planar cell polarity via noncanonical Wnt signaling. Proceedings of the National Academy of Sciences of the United States of America 9 39172791
2020 MicroRNA-503-3p affects osteogenic differentiation of human adipose-derived stem cells by regulation of Wnt2 and Wnt7b under cyclic strain. Stem cell research & therapy 9 32711579
2018 The Wnt7b/β-catenin signaling pathway is involved in the protective action of calcitonin gene-related peptide on hyperoxia-induced lung injury in premature rats. Cellular & molecular biology letters 9 29416550
2019 Narrowband UVB treatment induces expression of WNT7B, WNT10B and TCF7L2 in psoriasis skin. Archives of dermatological research 8 31089877
2019 The role of Wnt7B in the mediation of dentinogenesis via the ERK1/2 pathway. Archives of oral biology 8 31181411
2024 RBM39 Enhances Cholangiocarcinoma Growth Through EZH2-mediated WNT7B/β-catenin Pathway. Cellular and molecular gastroenterology and hepatology 7 39278404
2022 Bi-allelic variants in WNT7B disrupt the development of multiple organs in humans. Journal of medical genetics 7 35790350
2022 Inhibition of Wnt7b reduces the proliferation, invasion, and migration of colorectal cancer cells. Molecular biology reports 7 36472725
2021 circ_0082375 promotes the progression of glioma by regulating Wnt7B. Translational neuroscience 7 34868669
2021 Wnt7b Inhibits Osteoclastogenesis via AKT Activation and Glucose Metabolic Rewiring. Frontiers in cell and developmental biology 7 34881243
2007 Expression of MIG-6, WNT-9A, and WNT-7B during osteoarthritis. Annals of the New York Academy of Sciences 7 18056042
2024 m6A modification of CDC5L promotes lung adenocarcinoma progression through transcriptionally regulating WNT7B expression. American journal of cancer research 6 39113868
2024 Activation of the WNT7B/β-Catenin Pathway Initiates GLUT1 Expression and Promotes Aerobic Glycolysis in Colorectal Cancer Cells. Nutrition and cancer 6 39434562
2025 Regulatory Effects of the Wnt7b/β-Catenin/MMP-2 Signaling Pathway on Scleral Stiffness in Guinea Pigs With Form-Deprivation Myopia. Investigative ophthalmology & visual science 5 40338179
2023 circPTK2 promotes proliferation, migration and invasion of trophoblast cells through the miR-619/WNT7B pathway in preeclampsia. Molecular and cellular biochemistry 5 36913151
2019 MicroRNA-19b restricts Wnt7b to the hem, which induces aspects of hippocampus development in the avian forebrain. Development (Cambridge, England) 5 31578189
2021 miR-296-5p Inhibits the Secretion of Pulmonary Surfactants in Pulmonary Epithelial Cells via the Downregulation of Wnt7b/β-Catenin Signaling. BioMed research international 4 33490270
2021 The miR-34a/WNT7B modulates the sensitivity of cholangiocarcinoma cells to p53-mediated photodynamic therapy toxicity. Biochemical and biophysical research communications 4 34999254
2024 miR-199a-5p modulates choroidal neovascularization by regulating Wnt7b/Wnt/β-catenin signaling pathway. Journal of molecular histology 3 38662168
2024 LINC01605 promotes malignant phenotypes of cervical cancer via miR-149-3p/WNT7B axis. Gene 3 38734188
2023 Wnt7b expressed by hypertrophic chondrocytes is a stimulatory factor for endochondral ossification that is regulated by Smad4 activity. Development (Cambridge, England) 3 37539462
2022 Icariside II Attenuates Vascular Remodeling Via Wnt7b/CCND1 Axis. Journal of cardiovascular pharmacology 3 35170494
2021 Circ_0105346 Knockdown Inhibits Osteosarcoma Development via Regulating miR-1182/WNT7B Axis. Cancer management and research 3 33505171
2021 Evaluation of WNT Signaling Pathway Gene Variants WNT7B rs6519955, SFRP4 rs17171229 and RSPO2 rs611744 in Patients with Dupuytren's Contracture. Genes 3 34573275
2015 [Establishment of a chondrocyte degeneration model by over-expression of human Wnt7b gene in 293ft cell line]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 3 25818782
2025 Renal tubular epithelial cell related partial epithelial-mesenchymal transition in AAⅠ induced renal fibrosis via Wnt7b/β-catenin signaling. Frontiers in pharmacology 2 40432885
2024 A founder variant expands the phenotype of WNT7B-related PDAC syndrome. Clinical genetics 2 38417950
2023 Wnt7b: Is It an Important Factor in the Bone Formation Process after Calvarial Damage? Journal of clinical medicine 2 36769446
2021 How to Use Online Tools to Generate New Hypotheses for Mammary Gland Biology Research: A Case Study for Wnt7b. Journal of mammary gland biology and neoplasia 2 33625717
2020 Analysis of Wnt7B and BMP4 expression patterns in congenital pulmonary airway malformation. Pediatric pulmonology 2 31962011
2026 Piezo1 induces Wnt7b+ astrocytes transformation to modulate glial scar stiffness and neuro-regeneration after stroke. Theranostics 1 41346705
2025 Aristolochic acid I abnormally activates the wnt7b/β-catenin signaling pathway and affects the repair of renal tubules. Chemico-biological interactions 1 39921188
2025 ZNF831-YTHDF1-DNMT1/3a feedback loop regulates lung carcinogenesis and progression through WNT7B-FZD5-β-catenin signalling axis. Free radical biology & medicine 1 40975192
2024 Wnt7B enhances the osteogenic differentiation of lipopolysaccharide-stimulated human periodontal ligament stem cells and inhibits the M1 polarization of macrophages by binding FZD4. Molecular medicine reports 1 39301638
2023 Overexpression of Wnt7b antagonizes the inhibitory effect of dexamethasone on osteoblastogenesis of ST2 cells. Endokrynologia Polska 1 36704983
2023 Plasma Wnt7b protein in rheumatoid arthritis: Detection of interstitial lung disease. Immunobiology 1 37290224
2022 Wnt7b/β-catenin signaling pathway mediated by retinoid acid involved in the transdifferentiation of primary fetal alveolar epithelial type II cells. General physiology and biophysics 1 36454116
2015 [The changes of Wnt7b/β-catenin signaling pathway molecules in the differentiation of fetal alveolar epithelial type II cells]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 1 26429533

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