Affinage

GDF6

Growth/differentiation factor 6 · UniProt Q6KF10

Length
455 aa
Mass
50.7 kDa
Annotated
2026-04-28
57 papers in source corpus 27 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GDF6 is a secreted BMP-family ligand that patterns skeletal boundaries, maintains connective tissue matrices, and directs cell fate specification across multiple organ systems. It signals through type I receptors BMPR1A/ALK3 and ALK6 and type II receptors BMPR2, ACVR2A, and ACVR2B to activate canonical SMAD1/5/8 and non-canonical ERK1/2 pathways, driving chondrogenic and NP-like differentiation while inhibiting hypertrophic and osteogenic programs (PMID:14753743, PMID:32992671, PMID:23527555); its activity is antagonized by direct binding to noggin, and gain-of-function mutations conferring noggin resistance cause multiple synostoses syndrome (SYNS4) through hyperactive BMP/SMAD signaling and joint interzone disruption (PMID:26643732, PMID:36744814). Beyond classical BMP signaling, the GDF6 prodomain functions as a ligand for CD99, recruiting CSK to suppress Src kinase activity independently of the mature BMP domain (PMID:33147457). GDF6 mRNA stability is regulated by m6A epitranscriptomic machinery—stabilized by METTL3/IGF2BP1 and destabilized by FTO—and is post-transcriptionally repressed by miR-155-5p and miR-98 targeting its 3′ UTR (PMID:37041485, PMID:39474078, PMID:38074896, PMID:32045359).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1999 High

    The question of how GDF6 relates to BMP antagonism was resolved by showing that GDF6 directly binds noggin, which blocks its epidermal-inducing activity, and that GDF6 can form heterodimers with BMP2 only through cotranslation—establishing GDF6 as a noggin-regulated BMP ligand.

    Evidence Direct binding assay (GDF6–noggin), dissociated Xenopus cell fate assays, heterodimer cotranslation experiments

    PMID:10393114

    Open questions at the time
    • Affinity constants for GDF6–noggin vs other BMP–noggin pairs not determined
    • Heterodimer signaling properties not characterized
  2. 2003 High

    The in vivo requirement of GDF6 for skeletal patterning was established when Gdf6-null mice exhibited joint, ligament, cartilage, and coronal suture defects at sites distinct from Gdf5 mutants, and double mutants showed additive phenotypes, proving non-redundant roles within the GDF5/6/7 subgroup.

    Evidence Single and double Gdf5/Gdf6 knockout mice with skeletal phenotype analysis

    PMID:12606286

    Open questions at the time
    • Downstream transcriptional targets in joint interzone not identified
    • Mechanism distinguishing GDF5 vs GDF6 site specificity unknown
  3. 2006 High

    GDF6 was placed upstream of canonical SMAD1/5/8 signaling in ocular and neural development: its knockdown in zebrafish and Xenopus caused microphthalmia/coloboma, reduced pSMAD1/5/8, decreased Pax6 expression, and increased apoptosis, establishing GDF6 as essential for eye formation.

    Evidence Morpholino knockdown in zebrafish and Xenopus, pSmad1/5/8 immunostaining, TUNEL, Pax6 expression analysis

    PMID:17010201 PMID:17236135

    Open questions at the time
    • Direct receptor engagement in retinal progenitors not defined
    • Whether GDF6 acts cell-autonomously in retina versus via a relay not resolved
  4. 2008 Medium

    Identification of a GDF6 missense mutation causing Klippel-Feil syndrome extended the skeletal boundary-formation role to human vertebral segmentation, supported by Xenopus knockdown recapitulating anterior axial defects.

    Evidence Human mutation identification (p.Leu289Pro), Xenopus morpholino knockdown, expression analysis

    PMID:18425797

    Open questions at the time
    • Functional consequence of p.Leu289Pro on receptor binding or signaling not biochemically tested
    • Limited patient numbers
  5. 2009 Medium

    The requirement of GDF6 for connective tissue integrity was quantified: Gdf6-null mice had 33% lower tail tendon collagen and 45–50% reduced mechanical properties, establishing GDF6 as a regulator of tendon matrix modeling.

    Evidence Gdf6-null mouse, collagen quantification, biomechanical testing

    PMID:19248159

    Open questions at the time
    • Whether GDF6 acts directly on tenocytes or via paracrine signaling not resolved
    • Single anatomical site analyzed
  6. 2010 High

    GDF6 was shown to promote chondrogenic but not hypertrophic/osteogenic differentiation of mesenchymal progenitors, distinguishing its downstream program from BMP-2 and explaining its joint-preserving rather than bone-forming role.

    Evidence Adenoviral GDF6 transduction of C3H10T1/2 cells, differentiation marker profiling, comparison with BMP-2

    PMID:14753743

    Open questions at the time
    • Receptor-level basis for divergent signaling relative to BMP-2 not defined
  7. 2011 High

    A paradox was identified: GDF6 binds type I (ALK3, ALK6) and type II (ACVR2A, ACVR2B, BMPR2) receptors with affinities comparable to BMP-2 yet fails to activate SMAD1/5/8 in the same cells, instead inducing tendon-specific genes—revealing receptor-binding-independent divergence in signaling output.

    Evidence Quantitative receptor binding affinity assays, SMAD signaling assays, Thbs4/osteocalcin gene expression in C3H10T1/2 cells

    PMID:21702718

    Open questions at the time
    • Co-receptor or intracellular scaffolding differences not identified
    • Context-dependency of SMAD activation across cell types not systematically explored
  8. 2012 High

    The mechanism by which GDF6 maintains cranial suture patency was clarified: Gdf6-null mice showed premature coronal suture fusion via accelerated osteogenic differentiation (elevated ALP, Runx2) of suture mesenchyme, positioning GDF6 as an inhibitor of osteoblast commitment at suture boundaries.

    Evidence Gdf6-null mouse, ALP activity, Runx2 immunostaining, developmental staging of suture fusion

    PMID:22693558

    Open questions at the time
    • Whether GDF6 acts cell-autonomously on suture mesenchyme not shown
    • Interaction with other craniosynostosis-associated pathways (FGF, Wnt) not tested
  9. 2013 High

    GDF6 was found to direct adipocyte lineage commitment through BMPR1A and BMPR2/ACVR2A, requiring both SMAD4 and p38 MAPK, with Runx1t1 acting as a downstream transcriptional switch—broadening GDF6 function beyond skeletal boundaries to adipogenesis.

    Evidence GDF6 overexpression and RNAi of Smad4, p38 MAPK, receptors, and Runx1t1 in C3H10T1/2 cells

    PMID:23527555

    Open questions at the time
    • In vivo adipogenic role of GDF6 not validated
    • Whether p38 activation is direct or indirect not resolved
  10. 2015 High

    The gain-of-function mechanism for GDF6 p.Y444N was defined: this mutation renders GDF6 resistant to noggin antagonism and enhances SMAD1/5/8 signaling, causing multiple synostoses syndrome (SYNS4)—proving that the noggin–GDF6 balance is the critical rheostat for joint formation.

    Evidence BMP signaling reporter assays, noggin antagonism assays comparing WT and mutant GDF6, human genetic data

    PMID:26643732

    Open questions at the time
    • Structural basis for noggin resistance not determined
    • Whether other BMP antagonists (e.g. gremlin) are similarly affected not tested
  11. 2016 High

    GDF6 was placed downstream of Ror2/Wnt-PCP signaling in neural plate border specification: Ror2 depletion abolished local GDF6 upregulation and BMP activity at the neural plate border, and GDF6 was sufficient to rescue neural crest induction in Ror2 morphants.

    Evidence Xenopus Ror2 morpholino knockdown, GDF6 rescue, pSmad staining, neural plate border marker analysis

    PMID:27578181

    Open questions at the time
    • Direct transcriptional regulation of GDF6 by Ror2/PCP pathway not demonstrated
    • Mammalian conservation not tested
  12. 2020 High

    Multiple advances defined GDF6 signaling in disc biology and its post-transcriptional regulation: in nucleus pulposus cells GDF6 activates both SMAD1/5/8 and ERK1/2 for anabolic responses; miR-155-5p and miR-98 were validated as direct suppressors of GDF6 mRNA via 3′-UTR binding; and GDF6 knockout caused cochlear aplasia linked to distant cis-regulatory elements.

    Evidence Pathway inhibitor blocking studies in NP cells, dual-luciferase 3′UTR reporter assays for miR-155-5p and miR-98, Gdf6-null mouse cochlear phenotype, iPSC-derived otic cell expression analysis

    PMID:32045359 PMID:32369452 PMID:32992671 PMID:38074896

    Open questions at the time
    • Identity of m6A vs miRNA regulatory hierarchy on GDF6 mRNA not integrated
    • Long-range enhancer–promoter looping mechanism not structurally resolved
  13. 2020 High

    An entirely novel signaling modality was discovered: the GDF6 prodomain (not the mature BMP ligand) binds CD99 and recruits CSK to suppress Src activity; Klippel-Feil-associated prodomain mutations are hyperactive in this axis, revealing a BMP-independent signaling function for the GDF6 precursor.

    Evidence Co-IP/pulldown of GDF6 prodomain–CD99, CSK recruitment assay, Src activity measurement, growth arrest assay in Ewing sarcoma cells

    PMID:33147457

    Open questions at the time
    • Whether prodomain–CD99 signaling operates in skeletal tissues not tested
    • Stoichiometry and structural basis of prodomain–CD99 interaction unknown
    • Relationship between prodomain processing and dual signaling modes undefined
  14. 2023 High

    GDF6 mRNA was shown to be epitranscriptomically regulated: METTL3-mediated m6A methylation stabilizes GDF6 mRNA during dentinogenesis, and gain-of-function knock-in mice (p.Tyr443Asn) confirmed that enhanced GDF6/BMP signaling disrupts joint interzone formation at the transcriptomic level.

    Evidence MeRIP-seq and actinomycin-D stability assays in dental pulp stem cells; CRISPR knock-in mouse with RNA-seq of limb buds

    PMID:36744814 PMID:37041485

    Open questions at the time
    • Which m6A sites on GDF6 mRNA are functionally critical not mapped at nucleotide resolution
    • Transcriptomic changes in knock-in mice not validated at the protein level for all targets
  15. 2024 Medium

    The m6A regulatory circuit was extended: FTO demethylation destabilizes GDF6 mRNA, while IGF2BP1 acts as the m6A reader stabilizing it; FTO depletion increases GDF6 and type I interferon output in RSV-infected cells, linking GDF6 to innate immune regulation.

    Evidence FTO and IGF2BP1 knockdown, m6A-seq, mRNA stability assays, IFN and cytokine measurement in RSV-infected cells

    PMID:39474078

    Open questions at the time
    • Whether GDF6 directly drives IFN production or acts indirectly not resolved
    • Relevance of GDF6-IFN axis beyond RSV infection unknown
  16. 2025 Medium

    GDF6 was shown to exert cardioprotective anti-hypertrophic effects through a non-canonical cAMP/Epac1/AMPKα pathway, distinct from its classical BMP receptor signaling.

    Evidence AAV9-mediated cardiac GDF6 overexpression/knockdown in TAC mouse model, pharmacological AMPKα inhibition, Epac1 knockdown, neonatal rat ventricular myocytes

    PMID:41462947

    Open questions at the time
    • Receptor mediating cAMP/Epac1 activation by GDF6 in cardiomyocytes not identified
    • Single lab, awaits independent confirmation

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for GDF6's divergent signaling through the same receptors as BMP-2, the physiological contexts in which prodomain–CD99 versus mature-ligand–BMPR signaling predominate, and how m6A-dependent mRNA stabilization integrates with miRNA-mediated repression to set GDF6 protein levels in specific tissues.
  • No crystal structure of GDF6–receptor complex available
  • Prodomain cleavage regulation and tissue-specific processing not characterized
  • Integrated quantitative model of epitranscriptomic and miRNA regulation of GDF6 mRNA absent

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0098772 molecular function regulator activity 1
Localization
GO:0005576 extracellular region 4
Pathway
R-HSA-1266738 Developmental Biology 6 R-HSA-162582 Signal Transduction 6 R-HSA-8953854 Metabolism of RNA 2
Partners
ACVR2AACVR2BBMPR1ABMPR2CD99CSKIGF2BP1NOG

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 GDF6 (Xenopus ortholog) directly binds the neural inducer noggin, antagonizing its activity; GDF6 induces epidermis and inhibits neural tissue in dissociated cells, and this activity is blocked by noggin. GDF6 and BMP2 form heterodimers requiring cotranslation in the same cells. Direct binding assay (GDF6-noggin), dissociated cell fate assays, heterodimer formation by cotranslation Development (Cambridge, England) High 10393114
2003 Gdf6 null mutation in mice causes defects in joint, ligament, and cartilage formation at sites distinct from Gdf5 mutants (wrist, ankle, middle ear, coronal suture); double Gdf5/Gdf6 mutants show additive skeletal defects including loss of limb skeletal elements and scoliosis, establishing non-redundant roles for GDF5/6/7 subgroup members in skeletal boundary formation. Gene knockout (single and double null mice), skeletal phenotype analysis Developmental biology High 12606286
2006 Morpholino inhibition of gdf6a in zebrafish recapitulates chorioretinal coloboma, microphthalmia, and anophthalmia, establishing GDF6 as a key regulator of ocular development. Morpholino knockdown in zebrafish, phenotype analysis American journal of human genetics High 17236135
2006 GDF6 knockdown in Xenopus reduces eye size and retinal laminar structure, decreases Smad1/5/8 phosphorylation, reduces Pax6 expression domain, and increases apoptosis along the neural tube and retina, placing GDF6 upstream of canonical BMP/Smad signaling in neural and eye development. Morpholino knockdown (Xenopus), TUNEL staining, immunostaining for pSmad1/5/8 and Pax6 BMC developmental biology High 17010201
2008 GDF6 missense mutation p.Leu289Pro causes Klippel-Feil syndrome; GDF6 knockdown in Xenopus results in anterior axial defects consistent with vertebral segmentation role; GDF6 is expressed at boundaries of developing carpals, tarsals, and vertebrae and in the adult vertebral disc. Human mutation identification, Xenopus morpholino knockdown, expression analysis Human mutation Medium 18425797
2009 GDF6 null mutation causes substantially lower tail tendon collagen content (-33%) and 45-50% reduction in tendon material properties in mice, establishing GDF6 as required for tendon matrix modeling. Gdf6 null mouse, collagen quantification, mechanical testing Anatomical record (Hoboken, N.J. : 2007) Medium 19248159
2009 GDF6 heterozygous mutations in patients with ocular and vertebral anomalies were characterized by SOX9-reporter assay and western analysis; Gdf6+/- mice exhibit variable ocular phenotypes; zebrafish morphants show ocular and skeletal (tail, somite marker) defects with altered noggin1/noggin2 expression. SOX9-reporter assay, western blot, Gdf6+/- mouse, zebrafish morpholino KD, somite marker expression Human molecular genetics High 19129173
2010 Adenoviral BMP-13 (GDF6) transduction of C3H10T1/2 mesenchymal progenitor cells induces chondrogenic differentiation (Alcian blue staining, cartilage-specific markers) but fails to support hypertrophic chondrocyte differentiation or endochondral ossification, unlike BMP-2; BMPR-IB/ALK-6 expression is constitutive and not affected by BMP-13. Adenoviral transduction, RT-PCR, biochemical and histological analysis of differentiation markers, ALP assay Journal of bone and mineral research High 14753743
2011 Recombinant BMP12 (GDF6) and BMP13 bind type I BMPRs (ALK3, ALK6) and type II BMPRs (ACVR2A, ACVR2B, BMPR2) with similar affinities to BMP2, yet BMP12/13 do not activate SMAD1/5/8 signaling in C3H10T1/2 cells and instead dose-dependently induce tendon-specific Thbs4 expression without osteocalcin induction, indicating receptor-binding-independent divergence in downstream signaling. Receptor binding affinity assays, SMAD signaling assays, gene expression (Thbs4, osteocalcin) in C3H10T1/2 cells Growth factors (Chur, Switzerland) High 21702718
2012 Gdf6 is expressed in frontal bone primordia from E10.5-E12.5; Gdf6-/- mice show premature coronal suture fusion due to accelerated differentiation of suture mesenchyme prior to calvarial ossification onset, with increased ALP activity and Runx2 expression in suture mesenchyme, demonstrating that Gdf6 inhibits osteogenic differentiation of coronal suture mesenchyme. Gdf6 null mouse, ALP activity assay, Runx2 immunostaining, developmental staging PloS one High 22693558
2013 Overexpression of Gdf6 induces commitment of pluripotent mesenchymal C3H10T1/2 cells to the adipocyte lineage; this is mediated through type I receptor Bmpr1a and type II receptors Bmpr2 and Acvr2a; both Smad4 and p38 MAPK pathways are required; Runx1t1 is downregulated in committed pre-adipocytes and forced Runx1t1 expression blocks adipocytic commitment. Overexpression, RNAi silencing of Smad4/p38 MAPK, receptor knockdown, Runx1t1 forced expression The FEBS journal High 23527555
2015 A GDF6 missense variant (p.Y444N) in the region critical for binding to receptors and the BMP antagonist NOG causes gain-of-function: mutant GDF6 is a more potent stimulator of canonical BMP signaling (SMAD1/5/8) and is resistant to NOG-mediated antagonism, leading to loss of joint formation (multiple synostoses syndrome SYNS4). Human genetics, BMP signaling reporter assays, NOG antagonism assays, functional comparison of WT vs mutant GDF6 Journal of bone and mineral research High 26643732
2016 Ror2 is required for local upregulation of gdf6 at the neural plate border in Xenopus; Ror2 morphant embryos fail to activate BMP signaling (spatially restricted) at the neural plate border; Gdf6 is sufficient to rescue neural plate border specification in Ror2 morphants, placing Gdf6 downstream of Ror2/Wnt-PCP signaling and upstream of BMP activation for neural crest induction. Xenopus morpholino knockdown of Ror2, rescue with Gdf6, pSmad staining, neural plate border marker analysis Development (Cambridge, England) High 27578181
2020 GDF6 prodomain (not the BMP domain) is a ligand for CD99; GDF6 prodomain binding to CD99 extracellular domain recruits CSK (C-terminal Src kinase) to the YQKKK motif in CD99 intracellular domain, inhibiting Src activity; GDF6 silencing causes Src hyperactivation and p21-dependent growth arrest in Ewing sarcoma; two GDF6 prodomain mutants linked to Klippel-Feil syndrome are hyperactive in CD99-Src signaling. siRNA knockdown, Co-IP/pulldown (GDF6 prodomain-CD99), domain mapping, CSK recruitment assay, Src activity assay, growth arrest assay Cell reports High 33147457
2020 GDF6 signals through SMAD1/5/8 and ERK1/2 phosphorylation in human nucleus pulposus cells; recombinant GDF6 treatment induces anabolic response (increased matrix/NP-phenotypic markers, glycosaminoglycan production) in degenerate NP cells; blocking studies confirm both SMAD-dependent and SMAD-independent (ERK1/2) mechanisms. Recombinant GDF6 treatment, pSmad1/5/8 and pERK1/2 western blot, pathway inhibitor blocking studies, GAG assay, gene expression International journal of molecular sciences High 32992671
2020 High BMPR2 expression in adipose-derived stem cells correlates with enhanced SMAD1/5/8 signaling and greater GDF6 responsiveness; SMAD1/5/8 signaling is required for rhGDF6-induced NP-like differentiation, while ERK1/2 contributes to critical NP gene expression and aggrecan/type II collagen production. Receptor expression profiling, rhGDF6 treatment, SMAD1/5/8 and ERK1/2 inhibitor studies, NP marker gene expression and matrix production Journal of tissue engineering Medium 32489577
2020 Knockout of Gdf6 in mice causes cochlear aplasia; long-range cis-regulatory elements located ~350 kb downstream of GDF6 are required for its expression in the cochlea, as human deletions of this noncoding region cause reduced GDF6 expression (shown in patient iPSC-derived otic lineage cells) and cochlear aplasia. Gdf6 mouse knockout, iPSC-derived otic cells with GDF6 expression analysis, human genomic deletion mapping The Journal of clinical investigation High 32369452
2021 SCDAL lncRNA induces GDF6 expression via direct interaction with SNF5 at the GDF6 promoter; secreted GDF6 promotes endothelial angiogenesis via non-canonical VEGFR2 activation. lncRNA knockdown/overexpression, ChIP/interaction assays at GDF6 promoter, tube formation assay, VEGFR2 signaling analysis Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 34319658
2023 Overloading-induced PIEZO1 activation upregulates miR-155-5p, which suppresses GDF6 mRNA (and downstream SMAD2/3 signaling), causing chondrocyte senescence and OA; miR-155-5p inhibition or recombinant GDF6 rescues joint homeostasis and attenuates OA in vivo. Mouse OA models, PIEZO1 activation, miR-155-5p mimic/inhibitor, GDF6 supplementation, SMAD2/3 signaling assays, in vivo intra-articular injection Cellular signalling Medium 38508350
2023 METTL3-mediated m6A methylation stabilizes GDF6 mRNA in dental pulp stem cells; METTL3 knockdown impairs dentinogenesis differentiation while overexpression promotes it, and this is linked to increased GDF6 (and STC1) mRNA stability. MeRIP-seq, lentiviral METTL3 KD/OE, RNA stability assay (actinomycin D), ALP/alizarin red staining, direct pulp capping model BMC oral health Medium 37041485
2023 GDF6 gain-of-function knock-in mice (p.Tyr443Asn, orthologous to human p.Tyr444Asn) recapitulate SYNS4 joint fusion; embryonic analysis shows joint interzone formation defects and excess chondrogenesis; RNA sequencing reveals enhanced BMP signaling and bone formation pathways, confirming that increased GDF6/BMP activity disrupts joint morphogenesis. CRISPR knock-in mouse, skeletal phenotype analysis, embryonic forelimb joint interzone analysis, RNA sequencing of forelimb buds Journal of bone and mineral research High 36744814
2024 FTO-mediated m6A demethylation destabilizes GDF6 mRNA; depletion of FTO stabilizes GDF6 mRNA and enhances type I interferon production while reducing pro-inflammatory factors in RSV-infected cells; IGF2BP1 (m6A reader) binding is required for GDF6 mRNA stability and downstream IFN production. FTO KD, IGF2BP1 KD, m6A-seq, mRNA stability assays, IFN and cytokine measurement iScience Medium 39474078
2024 GDF6 overexpression in gastric cancer cells promotes EMT via the TGF-β/SMAD3 signaling pathway (upregulating phospho-SMAD3, N-cadherin, vimentin; downregulating E-cadherin); GDF6 silencing reverses these effects. GDF6 siRNA KD and overexpression, western blot for pSMAD3 and EMT markers, CCK-8, scratch, Transwell assays Pathology, research and practice Medium 38850874
2025 GDF6 activates AMPKα through the cAMP/Epac1 pathway to exert anti-hypertrophic cardioprotective effects; GDF6 KD aggravates and GDF6 OE attenuates pressure overload-induced cardiac hypertrophy in mice; AMPKα inhibition or Epac1 KD abolishes GDF6's protective effects. AAV9-mediated cardiac GDF6 OE/KD, TAC mouse model, pharmacological AMPKα inhibition, Epac1 KD, echocardiography, molecular signaling assays, NRVM in vitro Biomedicines Medium 41462947
2020 miR-155-5p from M1-polarized macrophage-derived exosomes directly binds the 3' UTR of GDF6 mRNA to suppress GDF6 protein expression, impairing HUVEC migration and tube formation; miR-155-5p antagomiR promotes angiogenesis and wound healing in diabetic mice by enhancing GDF6. Exosome isolation, high-throughput miRNA sequencing, dual-luciferase 3'UTR reporter assay, HUVEC functional assays, in vivo diabetic wound model Molecular therapy. Nucleic acids High 38074896
2020 miR-98 directly binds GDF6 (and FAPP2) mRNA 3'-UTR to negatively regulate their expression; miR-98 suppresses proliferation, viability, and migration of trophoblast cells; GDF6 knockdown inhibits miR-98-mediated trophoblast proliferation. Dual-luciferase 3'UTR reporter assay, western blot, RT-PCR, trophoblast cell functional assays (EdU, MTT, Transwell) Reproduction (Cambridge, England) Medium 32045359
2020 CRISPR/Cas9 knockout of Gdf6 attenuates migration of murine IMCD3 cells; this effect is rescued by wild-type but not mutant GDF6, establishing GDF6 as required for normal cell migration with variant-specific functional impairment. CRISPR/Cas9 KO, cell migration assay, rescue with WT vs mutant GDF6 European journal of human genetics Medium 32737436

Source papers

Stage 0 corpus · 57 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Multiple joint and skeletal patterning defects caused by single and double mutations in the mouse Gdf6 and Gdf5 genes. Developmental biology 272 12606286
2008 Mutations in GDF6 are associated with vertebral segmentation defects in Klippel-Feil syndrome. Human mutation 148 18425797
2006 GDF6, a novel locus for a spectrum of ocular developmental anomalies. American journal of human genetics 91 17236135
2009 Incomplete penetrance and phenotypic variability characterize Gdf6-attributable oculo-skeletal phenotypes. Human molecular genetics 84 19129173
1999 Xenopus GDF6, a new antagonist of noggin and a partner of BMPs. Development (Cambridge, England) 80 10393114
2003 A general approach for identifying distant regulatory elements applied to the Gdf6 gene. Genome research 77 12915490
2010 BMP12 and BMP13 gene transfer induce ligamentogenic differentiation in mesenchymal progenitor and anterior cruciate ligament cells. Cytotherapy 63 20334610
2010 Mutational screening of CHX10, GDF6, OTX2, RAX and SOX2 genes in 50 unrelated microphthalmia-anophthalmia-coloboma (MAC) spectrum cases. The British journal of ophthalmology 63 20494911
2009 BMP-13 emerges as a potential inhibitor of bone formation. International journal of biological sciences 57 19240811
2009 BMP13 prevents the effects of annular injury in an ovine model. International journal of biological sciences 55 19521550
2011 Bone morphogenetic protein (BMP)1-3 enhances bone repair. Biochemical and biophysical research communications 52 21453682
2004 Adenovirus mediated BMP-13 gene transfer induces chondrogenic differentiation of murine mesenchymal progenitor cells. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 51 14753743
2006 Eye and neural defects associated with loss of GDF6. BMC developmental biology 46 17010201
2006 Structure and protective effect of exopolysaccharide from P. Agglomerans strain KFS-9 against UV radiation. Microbiological research 43 16580187
2010 Genetic defects of GDF6 in the zebrafish out of sight mutant and in human eye developmental anomalies. BMC genetics 40 21070663
2011 Divergent activities of osteogenic BMP2, and tenogenic BMP12 and BMP13 independent of receptor binding affinities. Growth factors (Chur, Switzerland) 39 21702718
2009 Identification of a tendon phenotype in GDF6 deficient mice. Anatomical record (Hoboken, N.J. : 2007) 33 19248159
2014 Distinct effects of platelet-rich plasma and BMP13 on rotator cuff tendon injury healing in a rat model. The American journal of sports medicine 31 25193888
2023 Exosomal miRNA-155-5p from M1-polarized macrophages suppresses angiogenesis by targeting GDF6 to interrupt diabetic wound healing. Molecular therapy. Nucleic acids 30 38074896
2012 In vitro effects of bmp-2, bmp-7, and bmp-13 on proliferation and differentation of mouse mesenchymal stem cells. Biomedical sciences instrumentation 30 22846268
2015 A New Subtype of Multiple Synostoses Syndrome Is Caused by a Mutation in GDF6 That Decreases Its Sensitivity to Noggin and Enhances Its Potency as a BMP Signal. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 29 26643732
2012 The BMP ligand Gdf6 prevents differentiation of coronal suture mesenchyme in early cranial development. PloS one 28 22693558
2008 Unveiling the bmp13 enigma: redundant morphogen or crucial regulator? International journal of biological sciences 28 18797508
2021 A Novel Human Long Noncoding RNA SCDAL Promotes Angiogenesis through SNF5-Mediated GDF6 Expression. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 24 34319658
2020 GDF6-CD99 Signaling Regulates Src and Ewing Sarcoma Growth. Cell reports 23 33147457
2017 Differentiation of MSC and annulus fibrosus cells on genetically engineered silk fleece-membrane-composites enriched for GDF-6 or TGF-β3. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 20 29058815
2014 Leri's pleonosteosis, a congenital rheumatic disease, results from microduplication at 8q22.1 encompassing GDF6 and SDC2 and provides insight into systemic sclerosis pathogenesis. Annals of the rheumatic diseases 19 24442880
2013 Gdf6 induces commitment of pluripotent mesenchymal C3H10T1/2 cells to the adipocyte lineage. The FEBS journal 19 23527555
2020 miR-98 is involved in missed abortion by targeting GDF6 and FAPP2. Reproduction (Cambridge, England) 16 32045359
2020 Regenerative Response of Degenerate Human Nucleus Pulposus Cells to GDF6 Stimulation. International journal of molecular sciences 15 32992671
2005 Detection of potential GDF6 regulatory elements by multispecies sequence comparisons and identification of a skeletal joint enhancer. Genomics 15 15979840
2024 The PIEZO1/miR-155-5p/GDF6/SMAD2/3 signaling axis is involved in inducing the occurrence and progression of osteoarthritis under excessive mechanical stress. Cellular signalling 14 38508350
2020 Long-range cis-regulatory elements controlling GDF6 expression are essential for ear development. The Journal of clinical investigation 14 32369452
2018 Systemic inhibition of BMP1-3 decreases progression of CCl4-induced liver fibrosis in rats. Growth factors (Chur, Switzerland) 14 29482391
2016 Combined effects of engineered tendon matrix and GDF-6 on bone marrow mesenchymal stem cell-based tendon regeneration. Biotechnology letters 14 26956234
2016 Ror2 signaling is required for local upregulation of GDF6 and activation of BMP signaling at the neural plate border. Development (Cambridge, England) 14 27578181
2020 Exoproduction and characterization of a detergent-stable alkaline keratinase from Arthrobacter sp. KFS-1. Biochimie 12 32835736
2019 Lytic KFS-SE2 phage as a novel bio-receptor for Salmonella Enteritidis detection. Journal of microbiology (Seoul, Korea) 12 30706346
2017 Further delineation of the GDF6 related multiple synostoses syndrome. American journal of medical genetics. Part A 12 29130651
2020 High BMPR2 expression leads to enhanced SMAD1/5/8 signalling and GDF6 responsiveness in human adipose-derived stem cells: implications for stem cell therapies for intervertebral disc degeneration. Journal of tissue engineering 11 32489577
2013 A novel extended-spectrum β-lactamase, SGM-1, from an environmental isolate of Sphingobium sp. Antimicrobial agents and chemotherapy 11 23716045
2012 Klippel-Feil syndrome associated with situs inversus: description of a new case and exclusion of GDF1, GDF3 and GDF6 as causal genes. European journal of medical genetics 11 22522086
2023 METTL3 enhances dentinogenesis differentiation of dental pulp stem cells via increasing GDF6 and STC1 mRNA stability. BMC oral health 10 37041485
2021 GDF6 Knockdown in a Family with Multiple Synostosis Syndrome and Speech Impairment. Genes 10 34573339
2004 Comparative sequence analysis of the Gdf6 locus reveals a duplicon-mediated chromosomal rearrangement in rodents and rapidly diverging coding and regulatory sequences. Genomics 8 15475260
2020 Rare heterozygous GDF6 variants in patients with renal anomalies. European journal of human genetics : EJHG 7 32737436
2025 Effects of GDF6 on active protein synthesis by cells of degenerated intervertebral disc. European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society 6 39920317
2018 A Novel GDF6 Mutation in a Family with Multiple Synostoses Syndrome without Hearing Loss. Molecular syndromology 6 30733656
2025 IFNγ regulates ferroptosis in KFs by inhibiting the expression of SPOCD1 through DNMT3A. Cell death discovery 4 39820341
2024 GDF6 in gastric cancer upregulated by helicobacter pylori induces epithelial-mesenchymal translation via the TGF-β/SMAD3 signaling pathway. Pathology, research and practice 4 38850874
2024 The GDF6-FTO axis modulates the innate immune and inflammatory response to human respiratory syncytial virus. iScience 4 39474078
2023 Defective Joint Development and Maintenance in GDF6-Related Multiple Synostoses Syndrome. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 4 36744814
2025 Therapeutic Effects of GDF6-Overexpressing Mesenchymal Stem Cells through Upregulation of the GDF15/SIRT1 Axis in Age-Related Hearing Loss. Frontiers in bioscience (Landmark edition) 3 39862101
2014 Association of rs6982567 near GDF6 with neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in a Han Chinese cohort. BMC ophthalmology 3 25416513
2024 Transcriptomic profiling reveals key early response genes during GDF6-mediated differentiation of human adipose-derived stem cells to nucleus pulposus cells. JOR spine 2 38249721
2025 Dual-Faced Role of GDF6 in Cancer: Mechanistic Insights into Its Context-Dependent Regulation of Metastasis and Immune Evasion Across Human Malignancies. Current issues in molecular biology 1 40699648
2025 GDF6 Alleviates Pathological Cardiac Hypertrophy via AMPKα Signaling Pathway. Biomedicines 0 41462947