Affinage

FGF3

Fibroblast growth factor 3 · UniProt P11487

Length
239 aa
Mass
26.9 kDa
Annotated
2026-06-09
100 papers in source corpus 34 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 10/10 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FGF3 is a secreted heparin-binding growth factor that acts as a paracrine morphogen during embryogenesis, signaling preferentially through the FGFR2-IIIb isoform to drive otic, hindbrain, pituitary, and craniofacial patterning (PMID:8622866, PMID:11959820, PMID:11437442, PMID:12385757). The mature protein is secreted, glycosylated, and tethered to the cell surface and extracellular matrix through heparan sulfate, from which it can be displaced by soluble heparin; its C-terminal region determines receptor affinity, mitogenic potency, and transforming activity (PMID:8223431, PMID:8622866). FGF3 has an unusual dual subcellular fate: it is translated chiefly from an upstream CUG codon, and competing signals within the same protein—a cleaved signal peptide directing secretion versus a bipartite nuclear localization motif with upstream N-terminal sequences directing nuclear import—partition it between the secretory pathway and the nucleus (PMID:8076608). The mode of cell-surface presentation governs biological output, as anchoring FGF3 independently of heparan sulfate markedly increases its transforming potential (PMID:12084721). In development, FGF3 cooperates with FGF8 and FGF10 as an inductive signal: with FGF8 it establishes rhombomere 4 as a hindbrain signaling center patterning r5/r6, and with FGF10 it acts redundantly and dose-dependently for otic placode induction and otic vesicle formation (PMID:12135921, PMID:12121619, PMID:11959820, PMID:11437442, PMID:12385757, PMID:12810586, PMID:14623822, PMID:10769226). It refines dorsal otic patterning by restraining ventral expansion of Wnt3a and operates within a Hoxa1/Mafb→Fgf3→Gbx2 WNT cascade (PMID:17855431). FGF3 specifies adenohypophyseal progenitors and pituitary lineage boundaries from the ventral diencephalon, drives epibranchial placode neurogenesis from pharyngeal endoderm, and signals through MAPK/ERK to upregulate Pea3 and thereby Krox20 in the hindbrain (PMID:15229178, PMID:16077091, PMID:20553903, PMID:18514643). Along the posterior axis FGF3 restrains BMP signaling to coordinate neural tube closure and neural crest timing, while BMP reciprocally antagonizes FGF3 expression (PMID:18823972, PMID:27144312). Its transcription is controlled at the PS4A promoter element by GATA-4 and SOX7 as activators and SOX6—which recruits the co-repressor CtBP2 via a PLNLSS motif—as a repressor (PMID:11504872, PMID:15082719, PMID:11842118, PMID:8265348). Postnatally, vagal sensory neuron-derived FGF3 enhances glucose-stimulated insulin secretion, and dysregulated FGF3 promotes mammary tumorigenesis through an FGF3/FGFR1/STAT3 axis with direct FGF3–FGFR1 binding (PMID:39413782, PMID:37496658).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1993 High

    Establishing FGF3 as a bona fide secreted, heparin-binding, receptor-activating growth factor answered whether it functions extracellularly like other FGFs and mapped its activity determinants.

    Evidence COS-1 secretion and glycosylation analysis, heparin-Sepharose binding, NIH3T3 transformation and mitogenesis assays, and chimeric FGF3 constructs

    PMID:8223431

    Open questions at the time
    • Receptor isoform preference not yet defined
    • Endogenous developmental sites of action not addressed
  2. 1994 High

    Resolving the dual subcellular fate of FGF3 explained how a single CUG-initiated protein can be both secreted and nuclear, revealing competing trafficking signals within one polypeptide.

    Evidence In vitro translation, deletion/replacement mutagenesis, heterologous fusion proteins, and subcellular fractionation in COS-1 cells

    PMID:8076608

    Open questions at the time
    • Functional role of the nuclear pool not defined
    • Physiological regulation of CUG vs AUG initiation in vivo unknown
  3. 1996 High

    Defining FGFR2-IIIb as the preferred receptor and mapping C-terminal affinity determinants established the receptor specificity underlying FGF3 signaling.

    Evidence FGFR2-IIIb vs IIIc binding assays, Xenopus/zebrafish chimeric proteins, transformation and heparin displacement assays in COS-1/NIH3T3 cells

    PMID:8622866

    Open questions at the time
    • Structural basis of IIIb selectivity not resolved
    • In vivo receptor usage across tissues not tested
  4. 2001 High

    Dissecting the Fgf3 promoter answered how its transcription is positively and negatively controlled, identifying PS4A as the central regulatory hub and a GATA-4/SOX7 activator versus SOX6/CtBP2 repressor logic.

    Evidence DNase-I footprinting, deletion reporter assays in F9 cells, yeast one/two-hybrid, mammalian Co-IP, RNAi, and EMSA across multiple studies

    PMID:11504872 PMID:11842118 PMID:15082719 PMID:8265348

    Open questions at the time
    • How these factors are coordinated in specific developmental contexts unclear
    • Chromatin-level regulation not addressed
  5. 2002 High

    Genetic and pharmacological studies in zebrafish and mouse established FGF3, acting with FGF8 and FGF10, as the inductive signal for hindbrain segmentation and otic placode formation, defining its core morphogen role.

    Evidence Single and double morpholino knockdown, genetic double nulls, SU5402 time-window inhibition, cell transplantation, and ectopic expression with otic/rhombomere marker analysis

    PMID:10769226 PMID:11437442 PMID:11959820 PMID:12121619 PMID:12135921 PMID:12385757 PMID:12810586 PMID:14623822

    Open questions at the time
    • Relative contribution of secreted vs cell-surface FGF3 in vivo unresolved
    • Quantitative dose thresholds for distinct outcomes undefined
  6. 2007 High

    Epistasis in the mouse otic vesicle placed FGF3 in a WNT-initiated cascade, showing it restrains Wnt3a to focus inductive signals and patterns dorsal otic identity between Hoxa1/Mafb and Gbx2.

    Evidence Fgf3 null mouse analysis with Wnt3a expression and multi-gene epistasis against Hoxa1, Mafb, and Gbx2 mutants

    PMID:17855431

    Open questions at the time
    • Direct molecular link between FGF3 signaling and Wnt3a restriction unknown
    • Receptor mediating dorsal otic patterning not identified
  7. 2008 Medium

    Studies of pituitary and hindbrain development extended FGF3's role to lineage specification and target gene control, showing it specifies adenohypophyseal progenitors, sets pituitary lineage boundaries, and drives Pea3→Krox20 via MAPK/ERK.

    Evidence Zebrafish fgf3 mutant/morphant analysis with lineage markers, Shh epistasis, live POMC reporter imaging, chick morpholino knockdown and FGFR inhibition with Pea3/Krox20 analysis

    PMID:15229178 PMID:18514643 PMID:18823972 PMID:20553903

    Open questions at the time
    • Direct transcriptional targets of FGF3-driven ERK in each context not fully enumerated
    • Single-lab findings for several contexts
  8. 2016 High

    Mouse genetics established a reciprocal FGF3–BMP antagonism along the posterior axis, defining FGF3 as a restraint on BMP signaling that coordinates neural tube closure and neural crest timing.

    Evidence Fgf3 null mouse with Noggin and BMP receptor epistasis, in vitro BMP4 treatment of PSM explants, and neural crest/tube marker and proliferation analysis

    PMID:18823972 PMID:27144312

    Open questions at the time
    • Molecular mechanism by which FGF3 limits BMP signaling not defined
    • Receptor used in PSM-to-neuroepithelium signaling unknown
  9. 2023 Medium

    Newer work added postnatal and disease functions, showing vagal-derived FGF3 enhances insulin secretion, FGF3 acts as a dose-dependent axon guidance cue via FGFR1, and dysregulated FGF3 drives mammary tumorigenesis through direct FGF3–FGFR1 binding and STAT3/Akt signaling.

    Evidence Conditional vagal overexpression/ablation with glucose and GSIS assays, chick explant guidance assays with FGFR1 loss-of-function, and FGF3–FGFR1 Co-IP with shRNA knockdown and xenograft assays

    PMID:33684917 PMID:37496658 PMID:37834446 PMID:39413782

    Open questions at the time
    • FGFR1 (vs FGFR2-IIIb) usage across contexts not reconciled
    • Mechanism of concentration-dependent attraction vs repulsion unresolved
    • Tumor findings from single model/lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • The function of the nuclear FGF3 pool and how receptor choice (FGFR2-IIIb vs FGFR1) and cell-surface presentation are selected to produce distinct developmental and pathological outcomes remain unresolved.
  • No assigned function for nuclear FGF3
  • No unified model linking receptor/co-receptor context to specific cellular outcomes
  • Structural basis of signaling not determined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3 GO:0060089 molecular transducer activity 3 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005576 extracellular region 2 GO:0031012 extracellular matrix 2 GO:0005634 nucleus 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 2
Partners
FGF10FGF8FGFR1FGFR2

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 Mouse FGF3 is translated almost exclusively from an upstream CUG codon (rather than the AUG codon), producing a single protein that is distributed in both the nucleus and the secretory pathway. Secretion is mediated by cleavage adjacent to a signal peptide, whereas nuclear localization is determined by a classical bipartite nuclear localization motif together with upstream N-terminal sequences. These competing signals within the same protein determine its dual subcellular fate. Deletion and replacement mutants in reticulocyte lysates and transfected COS-1 cells; fusion to heterologous protein; subcellular fractionation The EMBO journal High 8076608
1993 Xenopus FGF3 (XFGF3) is secreted and glycosylated (31 kDa, signal-peptide cleaved), associates with cell surface and extracellular matrix via heparin-binding, and can be displaced by soluble heparin. It induces morphological transformation of NIH3T3 cells and stimulates DNA synthesis in cells expressing FGFR1 and FGFR2 isoforms. Chimeric proteins between XFGF3 and mouse FGF3 showed that the C-terminal region determines differences in receptor affinity, mitogenic potency, and transforming activity. COS-1 cell transfection, conditioned medium assays, heparin-Sepharose binding, NIH3T3 transformation assay, C57MG/BALB/MK mitogenesis assay, chimeric construct analysis The EMBO journal High 8223431
1996 Zebrafish FGF3 (ZFGF3) is secreted as a heterogeneous set of glycoproteins (29–30.5 kDa), associates strongly with extracellular matrix, and binds the IIIb isoform of FGFR2 with higher affinity than the IIIc isoform (similar to mouse FGF3). Hybrid proteins between Xenopus and zebrafish FGF3 implicate the C-terminal region in determining receptor affinity differences, mitogenic potency, and transforming activity. COS-1 cell transfection, receptor binding assays with FGFR2-IIIb vs IIIc, NIH3T3 transformation assay, chimeric construct analysis, heparin displacement Oncogene High 8622866
2001 SOX6 binds the key regulatory element PS4A in the Fgf-3 promoter and strongly represses Fgf-3 transcription. SOX6 recruits the co-repressor CtBP2 via a short PLNLSS motif, and SOX6 binding to CtBP2 is required for co-operative repression of the Fgf-3 promoter through PS4A. Yeast one-hybrid screen, reporter gene assays, yeast two-hybrid, co-immunoprecipitation in mammalian cells, mutational analysis of SOX6, in situ hybridization, co-expression in NIH3T3 cells Nucleic acids research High 11504872
2004 SOX7 activates Fgf-3 transcription by binding the PS4A element of the Fgf-3 promoter, competing with GATA-4 for PS4A occupancy. In GATA-4-deficient ES cells, Fgf-3 expression upon differentiation depends on SOX7, as shown by RNAi knockdown of Sox7. SOX2, by contrast, is a poor activator and negatively modulates GATA-4-driven Fgf-3 activation when co-expressed. Reporter gene assays, RNAi knockdown, co-expression studies in F9 and ES cells, nuclear extract complexes on PS4A, in situ hybridization The Journal of biological chemistry High 15082719
2002 GATA-4 binds two sites in the Fgf-3 promoter: PS4A (positive regulatory element) and PS13 (negative regulatory element near P3). Efficient binding to PS4A requires both zinc fingers and the basic domain of GATA-4 engaging a second flanking sequence, and this dual-zinc-finger binding is essential for Fgf-3 promoter activation. PS13 negative activity depends on its proximity to the transcription initiation site. Mutational analysis of GATA-4 truncation deletions, reporter gene assays, DNase-I footprinting, EMSA/DNA bending assays, promoter deletion constructs Nucleic acids research High 11842118
1993 The Fgf-3 promoter contains at least two positive and three negative regulatory elements. The PS4A element is essential for promoter activity in both undifferentiated and differentiated F9 cells, and deletions encompassing PS4A abolish retinoic acid inducibility and basal promoter activity. Stable and transient transfection of CAT reporter constructs, progressive and targeted deletion mutants, DNase-I footprinting in F9 embryonal carcinoma cells Nucleic acids research High 8265348
2004 A 5.7-kb enhancer upstream of mouse Fgf3 mediates embryonic expression in the midbrain, hindbrain, surface ectoderm, dorsal root ganglia, and CNS. Sonic hedgehog (Shh) signaling is required for Fgf3 expression in ventral CNS and DRG (Shh-dependent), whereas expression in cranial ganglion cells is Shh-independent. Transgenic reporter mice carrying Fgf3 genomic regions; deletional analysis; breeding into Shh mutant background; in situ hybridization Developmental dynamics Medium 15108308
2002 In zebrafish, FGF3 and FGF8 are both expressed in rhombomere 4 (r4) and together are required for development of adjacent rhombomeres 5 and 6. Transplantation of r4 cells or misexpression of either FGF3 or FGF8 can induce r5/r6 marker expression, establishing r4 as an FGF-mediated signaling center for early hindbrain patterning. Antisense morpholino knockdown, cell transplantation, misexpression experiments, time-lapse imaging, in situ hybridization for r5/r6 markers Development (Cambridge, England) High 12121619 12135921
2002 In zebrafish, combined loss of Fgf3 and Fgf8 via morpholino knockdown causes complete failure of otic placode formation and absence of early placode markers (pax2.1, dlx3), without affecting cell division or death. Either factor alone produces only partial reduction; the temporal requirement for FGF signaling is between 60% epiboly and tailbud stages. The earliest otic event, pax8 expression, does not require Fgf3/Fgf8, placing their action downstream of initial otic territory specification. Antisense morpholino knockdown (fgf3 and fgf8 single and double), FGFR inhibitor SU5402 time-window experiments, otic marker in situ hybridization, cell death/proliferation assays Development (Cambridge, England) High 11437442 11959820 12385757
2003 In mice, Fgf3 and Fgf10 act redundantly and in a dose-sensitive manner for otic placode induction: single mutants have partial defects, but double Fgf3/Fgf10 mutants fail to form otic vesicles. Fgf3 is expressed in hindbrain neurectoderm while Fgf10 is expressed in underlying mesenchyme, indicating that FGF signals for otic induction emanate from both sources. Genetic double knockout (Fgf3 and Fgf10 null alleles), compound heterozygote allelic series, otic marker gene expression analysis, cell proliferation and survival assays Development (Cambridge, England) High 12810586 14623822
2000 Ectopic expression of FGF3 in chick embryos induces formation of ectopic otic placodes expressing otic marker genes, which subsequently form vesicles with inner ear gene expression patterns. FGF2 under the same conditions has no effect, demonstrating specificity of FGF3 in inducing inner ear fate. In ovo electroporation-based gene transfer for ectopic FGF3 expression in chick, ectopic FGF2 control, otic marker in situ hybridization Development (Cambridge, England) Medium 10769226
2007 In mouse, Fgf3 expressed in hindbrain neurectoderm is required for dorsal otic patterning and endolymphatic duct formation. Fgf3 mutants show altered molecular patterning of the otic vesicle, and Fgf3 prevents ventral expansion of r5-6 Wnt3a, thereby focusing inductive WNT signals on the dorsal otic vesicle. Epistasis analysis places Fgf3 between hindbrain-expressed Hoxa1/Mafb and otic vesicle-expressed Gbx2 in the WNT-initiated cascade for dorsal otic patterning. Fgf3 null mouse genetic analysis, morphological and molecular otic patterning markers, Wnt3a expression analysis, genetic epistasis with Hoxa1, Mafb, and Gbx2 mutants Development (Cambridge, England) High 17855431
2004 In zebrafish, Fgf3 signaling from the ventral diencephalon is required non-cell-autonomously for expression of pituitary specification genes (lim3, pit1) in adenohypophyseal progenitor cells. Without Fgf3, early specification fails and adenohypophyseal cells subsequently die by apoptosis. Shh can induce adenohypophyseal cells ectopically but cannot rescue pituitary development in fgf3 mutants, indicating Fgf3 does not act via Shh. lia/fgf3 null mutant analysis, in situ hybridization for pituitary markers, epistasis with Shh pathway (Shh rescue experiments), apoptosis assays Development (Cambridge, England) High 15229178
2005 In zebrafish, Fgf3 derived specifically from pharyngeal endodermal pouches is required for neurogenesis (not initial induction) of epibranchial placodes. Tissue transplants demonstrate endoderm is the cellular source of the neurogenic signal. Ectopic fgf3 expression is sufficient to induce phox2a-positive neurons even in endoderm-deficient embryos, but neither endoderm nor Fgf3 is required for initial placode induction (foxi1 expression is unaffected). Morpholino knockdown of fgf3, endoderm ablation, mosaic cell transplantation, ectopic fgf3 overexpression, placode marker in situ hybridization Development (Cambridge, England) High 16077091
2010 In chick hindbrain, FGF3 (acting through the MAPK/Erk1/2 pathway) is required for upregulation of the ETS-domain transcription factor Pea3, which in turn is necessary for expression of Krox20 in rhombomeres 3 and 5. FGF signaling is a major contributor to ERK1/2 activation and downstream Pea3/Erm target expression in the hindbrain. Morpholino knockdown, pharmacological FGFR inhibition, in situ hybridization for FGF pathway components (ligands, receptors, MAPK components), Krox20 and Pea3 expression analysis Developmental biology Medium 20553903
2008 In chick hindbrain, BMP activity antagonizes FGF3 expression: blocking follistatin translation with morpholinos or overexpressing BMP strongly inhibits FGF3 expression, while adding follistatin increases FGF3 levels. FGF3 expression also requires FGF activity itself, suggesting an autoregulatory loop. This BMP-FGF3 antagonism is required for correct expression of Krox20, Hoxb1, and EphA4. Morpholino knockdown of follistatin, BMP overexpression, follistatin protein addition, in situ hybridization for FGF3 and segmentation genes Developmental biology Medium 18823972
2016 In mouse, PSM-derived FGF3 restrains BMP signaling in the adjacent neuroepithelium. Loss of FGF3 elevates BMP signals, causing increased neuroepithelium proliferation, delayed neural tube closure, and premature neural crest specification. Increasing BMP signaling (by removing one Noggin copy in Fgf3 mutants) exacerbates all phenotypes; decreasing BMP signaling (by removing BMP receptor) alleviates them. Elevated BMP4 depletes PSM progenitors in vitro, phenocopying the Fgf3 mutant axis defect. Fgf3 null mouse, genetic epistasis with Noggin and BMP receptor mutants, BMP4 in vitro treatment of PSM explants, neural crest/tube marker analysis, apoptosis/proliferation assays PLoS genetics High 27144312
1998 FGF3 localizes to the otocyst epithelium in mouse, and antisense oligonucleotides against FGF3 suppress otic capsule chondrogenesis in cultured periotic mesenchyme, establishing FGF3 as an otocyst-derived signal capable of initiating chondrogenesis of surrounding mesenchyme. Endogenous FGF3 localization (immunostaining), antisense oligonucleotide knockdown in periotic mesenchyme/otocyst co-culture system, chondrogenesis assay Growth factors (Chur, Switzerland) Medium 9570039
2002 Cell-surface-associated FGF3 (via heparan sulfate proteoglycan) is required for NIH3T3 cell transformation: dominant-negative FGFR2(IIIb) reverts the transformed phenotype more efficiently than IIIc, consistent with FGF3's higher affinity for the IIIb isoform. Attaching FGF3 to a GPI membrane anchor (independent of heparan sulfate) greatly increases its transforming potential, indicating that the mode of cell-surface presentation determines biological activity. Dominant-negative FGFR2(IIIb vs IIIc) expression in transformed DMI cells, GPI-anchored FGF3 mutant construction and transformation assay, heparin displacement, soft agar anchorage-independent growth The Journal of biological chemistry Medium 12084721
2008 In zebrafish, FGF3 signal from the ventral diencephalon delineates the melanotrope/corticotrope lineage boundary in the developing pituitary. Hypomorphic FGF3 morpholino knockdown specifically defects pars intermedia POMC cells while leaving pars distalis POMC, growth hormone, and prolactin expression intact. This lineage-specific role is independent of Lim3/Pit1 expression, indicating a function distinct from early progenitor specification. Hypomorphic fgf3 morpholino knockdown, time-lapse confocal live imaging with GFP:pomc reporter zebrafish, in situ hybridization for pituitary lineage markers Developmental biology Medium 18514643
2008 In Ciona intestinalis, FGF3 expressed in the floor plate of the developing nerve cord directs notochord convergent extension (CE) via non-MAPK FGF signaling. A dominant-negative FGF receptor suppresses polarized actin-rich protrusions in notochord cells, resulting in defective CE. In Xenopus mesoderm explants, inhibiting FGF signaling perturbs CE and disrupts membrane localization of Dishevelled (Dsh), a PCP/CE regulator, placing FGF3 upstream of PCP components. Dominant-negative FGFR expression in Ciona, inhibition of Ciona FGF3 activity, actin protrusion imaging, Xenopus CE explant assay, Dishevelled membrane localization Development (Cambridge, England) Medium 19036800
2019 In zebrafish, Fgf3 controls the number of serotonergic and dopaminergic CSF-contacting cells in the posterior hypothalamus by regulating proliferation and cell survival. Fgf3 acts via the ETS-domain transcription factor etv5b (a known FGF downstream target) to control serotonergic progenitor proliferation. Loss of fgf3 also upregulates its own expression, suggesting a self-compensatory mechanism. Fgf3 morpholino knockdown (null mutant analysis), immunostaining for serotonergic/dopaminergic/neuroendocrine markers, proliferation and apoptosis assays, etv5b expression analysis, hypothalamic transcriptome analysis Biology open Medium 31036752
2024 Fgf3 mRNA is upregulated in mouse vagal ganglia under acute metabolic stress. Vagal sensory neuron-derived FGF3 enhances glucose-stimulated insulin secretion (GSIS) and improves glucose metabolism. Restriction of Fgf3 overexpression to pancreas-projecting vagal sensory neurons recapitulates the insulinotropic effect, and genetic ablation of Fgf3 in pancreatic vagal afferents exacerbates high-fat diet-induced glucose intolerance and blunts GSIS. Conditional vagal sensory overexpression and genetic ablation of Fgf3, glucose tolerance tests, GSIS assays, electrostimulation of vagal afferents Developmental cell High 39413782
2023 FGF3 expressed in the chick ventral diencephalon (hypothalamus) acts as a concentration-dependent guidance cue for thalamocortical axons (TCAs): 100 ng/mL is attractant while 500 ng/mL is repellent. Inhibition of FGF3 function disrupts correct navigation of thalamic axons in vitro. In vitro chick explant guidance assays with recombinant FGF3 at different concentrations, inhibition of FGF3 signaling, expression analysis Developmental neuroscience Medium 33684917
2023 FGF3 expressed in the chick hypothalamus acts as a chemorepellent for neighboring prethalamic GABAergic axons. This guidance function is mediated through FGFR1 downstream signaling, as demonstrated by gene expression analysis and FGFR1 loss-of-function studies. In vitro chick explant guidance assays, FGF3 inhibition, FGFR1 expression analysis, FGFR1 loss-of-function, GABAergic axon tracing International journal of molecular sciences Medium 37834446
2023 In TA2 mice, MMTV-activated FGF3 promotes spontaneous mammary tumorigenesis via the FGF3/FGFR1/STAT3 signaling pathway. FGF3 physically binds FGFR1 (demonstrated by co-immunoprecipitation). FGF3 or FGFR1 knockdown decreases STAT3 and Akt phosphorylation. STAT3 and Akt mutually activate each other's phosphorylation, and inhibiting either increases FGFR1 expression. Co-immunoprecipitation of FGF3-FGFR1, shRNA knockdown of FGF3 and FGFR1, pharmacological STAT3/Akt inhibitors, proliferation/migration/invasion assays, xenograft tumor assay Frontiers in oncology Medium 37496658
2012 In parthenogenetic mouse embryos, Fgf3 is strongly upregulated and drives excessive Fgfr2 phosphorylation, which promotes primitive endoderm differentiation at the expense of epiblast identity (increased Gata4, decreased Sox2/Nanog). Inhibition of Fgfr2 with SU5402 in parthenotes restores normal Nanog/Gata4 levels without affecting Fgf3 expression, placing Fgf3 upstream of Fgfr2 in this pathway. FGFR2 inhibition with SU5402, immunostaining for lineage markers (Sox2, Nanog, Gata4), RT-qPCR for Fgf3/Fgfr2, analysis of Fgfr2 phosphorylation Developmental dynamics Medium 22930543
1998 FGF-3 (but not FGF-4) expressed in mouse mammary myoepithelial cells strongly stimulates production of pro-MMP-9 and pro-MMP-2, and upregulates plasminogen activators, contributing to matrix invasion. FGF-3-producing cells are invasive in Matrigel-coated chambers. FGF-4 has no effect on these protease secretions. Retroviral FGF-3 and FGF-4 expression in EF43 cells, Matrigel invasion assay, gelatin zymography for MMPs, plasminogen activator assays, tumorigenicity assays in syngeneic mice Oncogene Medium 9798677
2015 Fgf3 expression in zebrafish pharyngeal pouches is regulated downstream of Wnt5b/Wntless (Wls) secretion. In wls morphants and wnt5b mutants, fgf3 expression is reduced in pharyngeal pouches along the anteroposterior axis. Introducing fgf3 mRNA rescues jaw cartilage defects in Wnt5b- and Wls-deficient larvae. Wls is required for Wnt5b but not Wnt11 secretion in pharyngeal tissue, and fgf3 regulates chondrogenic cell proliferation downstream of Wnt5b/Wls. Morpholino knockdown of wls and wnt9a/wnt11, wnt5b mutant analysis, fgf3 mRNA rescue, cell proliferation assays, pharyngeal cartilage staining Journal of cell science Medium 25934698

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Fgf3 and Fgf10 are required for mouse otic placode induction. Development (Cambridge, England) 239 12810586
2001 Zebrafish fgf3 and fgf8 encode redundant functions required for otic placode induction. Developmental biology 211 11437442
2000 Associations of FGF-3 and FGF-10 with signaling networks regulating tooth morphogenesis. Developmental dynamics : an official publication of the American Association of Anatomists 209 11066089
2002 Fgf3 and Fgf8 are required together for formation of the otic placode and vesicle. Development (Cambridge, England) 202 11959820
2002 Fgf8 and Fgf3 are required for zebrafish ear placode induction, maintenance and inner ear patterning. Mechanisms of development 187 12385757
2002 FGF3 and FGF8 mediate a rhombomere 4 signaling activity in the zebrafish hindbrain. Development (Cambridge, England) 186 12135921
2003 Requirements for FGF3 and FGF10 during inner ear formation. Development (Cambridge, England) 172 14623822
1995 Multiple roles for FGF-3 during cranial neural development in the chicken. Development (Cambridge, England) 161 7789270
2007 Duplication of FGF3, FGF4, FGF19 and ORAOV1 causes hair ridge and predisposition to dermoid sinus in Ridgeback dogs. Nature genetics 156 17906623
2002 Establishment of hindbrain segmental identity requires signaling by FGF3 and FGF8. Current biology : CB 129 12121619
1992 Developmental expression of the Xenopus int-2 (FGF-3) gene: activation by mesodermal and neural induction. Development (Cambridge, England) 128 1425349
2013 FGF3/FGF4 amplification and multiple lung metastases in responders to sorafenib in hepatocellular carcinoma. Hepatology (Baltimore, Md.) 127 22890726
2003 Fgf3 and Fgf8 dependent and independent transcription factors are required for otic placode specification. Development (Cambridge, England) 122 12668634
1996 The role of FGF-3 in early inner ear development: an analysis in normal and kreisler mutant mice. Developmental biology 114 8631508
1994 Competition between nuclear localization and secretory signals determines the subcellular fate of a single CUG-initiated form of FGF3. The EMBO journal 110 8076608
2000 Induction of inner ear fate by FGF3. Development (Cambridge, England) 109 10769226
2004 Fgf3 signaling from the ventral diencephalon is required for early specification and subsequent survival of the zebrafish adenohypophysis. Development (Cambridge, England) 106 15229178
2003 Unique and combinatorial functions of Fgf3 and Fgf8 during zebrafish forebrain development. Development (Cambridge, England) 106 12900450
2007 Differential requirements for FGF3, FGF8 and FGF10 during inner ear development. Developmental biology 82 17601531
2007 Fgf3 is required for dorsal patterning and morphogenesis of the inner ear epithelium. Development (Cambridge, England) 77 17855431
1998 Expression and functions of FGF-3 in Xenopus development. The International journal of developmental biology 76 9879707
1996 Expression of Fgf-3 in relation to hindbrain segmentation, otic pit position and pharyngeal arch morphology in normal and retinoic acid-exposed mouse embryos. Anatomy and embryology 74 8800419
1996 Gene defect in hypodontia: exclusion of EGF, EGFR, and FGF-3 as candidate genes. Journal of dental research 65 8831628
2001 SOX6 binds CtBP2 to repress transcription from the Fgf-3 promoter. Nucleic acids research 64 11504872
2005 Endoderm-derived Fgf3 is necessary and sufficient for inducing neurogenesis in the epibranchial placodes in zebrafish. Development (Cambridge, England) 58 16077091
2008 FGF3 in the floor plate directs notochord convergent extension in the Ciona tadpole. Development (Cambridge, England) 53 19036800
2002 An expanded domain of fgf3 expression in the hindbrain of zebrafish valentino mutants results in mis-patterning of the otic vesicle. Development (Cambridge, England) 53 12399318
2004 SOX7 and GATA-4 are competitive activators of Fgf-3 transcription. The Journal of biological chemistry 50 15082719
1998 Crouzon-like craniofacial dysmorphology in the mouse is caused by an insertional mutation at the Fgf3/Fgf4 locus. Developmental dynamics : an official publication of the American Association of Anatomists 49 9626498
1994 Targeted disruption of int-2 (fgf-3) causes developmental defects in the tail and inner ear. Molecular reproduction and development 47 7999362
2009 Modulation of Fgf3 dosage in mouse and men mirrors evolution of mammalian dentition. Proceedings of the National Academy of Sciences of the United States of America 46 20018768
2007 SNP genome scanning localizes oto-dental syndrome to chromosome 11q13 and microdeletions at this locus implicate FGF3 in dental and inner-ear disease and FADD in ocular coloboma. Human molecular genetics 46 17656375
1993 Amplified region of chromosome band 11q13 in breast and squamous cell carcinomas encompasses three CpG islands telomeric of FGF3, including the expressed gene EMS1. Genes, chromosomes & cancer 44 7685625
1996 The zebrafish Fgf-3 gene: cDNA sequence, transcript structure and genomic organization. Gene 43 8654946
2011 Redundant and dosage sensitive requirements for Fgf3 and Fgf10 in cardiovascular development. Developmental biology 41 21664901
2008 Homozygous FGF3 mutations result in congenital deafness with inner ear agenesis, microtia, and microdontia. Clinical genetics 41 18435799
2016 An FGF3-BMP Signaling Axis Regulates Caudal Neural Tube Closure, Neural Crest Specification and Anterior-Posterior Axis Extension. PLoS genetics 40 27144312
2001 Phenotypic consequences of lung-specific inducible expression of FGF-3. Proceedings of the National Academy of Sciences of the United States of America 32 11331772
1993 FGF3 from Xenopus laevis. The EMBO journal 32 8223431
1993 First experience with FGF-3 (INT-2) amplification in women with epithelial ovarian cancer. British journal of cancer 31 8494710
2008 Inhibition of BMPs by follistatin is required for FGF3 expression and segmental patterning of the hindbrain. Developmental biology 30 18823972
2009 Boundary cells regulate a switch in the expression of FGF3 in hindbrain rhombomeres. BMC developmental biology 29 19232109
2008 Syndromic congenital sensorineural deafness, microtia and microdontia resulting from a novel homoallelic mutation in fibroblast growth factor 3 (FGF3). European journal of human genetics : EJHG 28 18701883
1998 FGF-3 and FGF-4 elicit distinct oncogenic properties in mouse mammary myoepithelial cells. Oncogene 28 9798677
2017 Hypomethylated Fgf3 is a potential biomarker for early detection of oral cancer in mice treated with the tobacco carcinogen dibenzo[def,p]chrysene. PloS one 26 29073177
2010 Analysis of expression and function of FGF-MAPK signaling components in the hindbrain reveals a central role for FGF3 in the regulation of Krox20, mediated by Pea3. Developmental biology 25 20553903
1996 Secretion and mitogenic activity of zebrafish FGF3 reveal intermediate properties relative to mouse and Xenopus homologues. Oncogene 24 8622866
2014 BMP4 and FGF3 haplotypes increase the risk of tendinopathy in volleyball athletes. Journal of science and medicine in sport 22 24661680
2004 Regulatory analysis of the mouse Fgf3 gene: control of embryonic expression patterns and dependence upon sonic hedgehog (Shh) signalling. Developmental dynamics : an official publication of the American Association of Anatomists 22 15108308
2002 Inducible expression of FGF-3 in mouse mammary gland. Proceedings of the National Academy of Sciences of the United States of America 22 12169667
2015 Control of Wnt5b secretion by Wntless modulates chondrogenic cell proliferation through fine-tuning fgf3 expression. Journal of cell science 21 25934698
2010 A FGF3 mutation associated with differential inner ear malformation, microtia, and microdontia. The Laryngoscope 21 19950373
2005 Comparative genomics on mammalian Fgf3-Fgf4 locus. International journal of oncology 21 15942670
2000 Detection of c-erbB-2 and FGF-3 (INT-2) gene amplification in epithelial ovarian cancer. International journal of oncology 21 10853025
1994 Int-2/FGF3 amplification is a better independent predictor of relapse than c-myc and c-erbB-2/neu amplifications in primary human breast cancer. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 21 7892157
1993 Activation of both Wnt-1 and Fgf-3 by insertion of mouse mammary tumor virus downstream in the reverse orientation: a reappraisal of the enhancer insertion model. Virology 21 8386870
2011 Expression of hindbrain boundary markers is regulated by FGF3. Biology open 20 23213398
1995 The proto-oncogene FGF-3 is constitutively expressed in tumorigenic, but not in non-tumorigenic, clones of a human colon carcinoma cell line. Oncogene 20 7784081
2011 Variable expressivity of FGF3 mutations associated with deafness and LAMM syndrome. BMC medical genetics 19 21306635
1993 Identification of positive and negative regulatory elements involved in the retinoic acid/cAMP induction of Fgf-3 transcription in F9 cells. Nucleic acids research 19 8265348
2016 Fgf3 and Fgf16 expression patterns define spatial and temporal domains in the developing chick inner ear. Brain structure & function 18 26995070
2013 Candidate gene studies in hypodontia suggest role for FGF3. European archives of paediatric dentistry : official journal of the European Academy of Paediatric Dentistry 18 23549991
2013 Fgf3 and Fgf10a work in concert to promote maturation of the epibranchial placodes in zebrafish. PloS one 17 24358375
2002 Ectopic expression of FGF-3 results in abnormal prostate and Wolffian duct development. Oncogene 17 11896623
2013 Fgf22 regulated by Fgf3/Fgf8 signaling is required for zebrafish midbrain development. Biology open 16 23789101
1998 Role of FGF3 in otic capsule chondrogenesis in vitro: an antisense oligonucleotide approach. Growth factors (Chur, Switzerland) 16 9570039
2013 Increased FGF3 and FGF4 gene dosage is a risk factor for craniosynostosis. Gene 15 24120895
2022 LY2874455 and Abemaciclib Reverse FGF3/4/19/CCND1 Amplification Mediated Gefitinib Resistance in NSCLC. Frontiers in pharmacology 14 35814257
2008 Differential requirements for Fgf3 and Fgf8 during mouse forebrain development. Developmental dynamics : an official publication of the American Association of Anatomists 14 18942154
2000 The zebrafish fth1, slc3a2, men1, pc, fgf3 and cycd1 genes define two regions of conserved synteny between linkage group 7 and human chromosome 11q13. Gene 14 11167010
1996 Aberrant FGF-2, FGF-3, FGF-4 and C-erb-B2 gene copy number in human ovarian, breast and endometrial tumours. Growth factors (Chur, Switzerland) 14 8962718
2015 Screening a novel FGF3 antagonist peptide with anti-tumor effects on breast cancer from a phage display library. Molecular medicine reports 13 26323695
2008 In vivo time-lapse imaging delineates the zebrafish pituitary proopiomelanocortin lineage boundary regulated by FGF3 signal. Developmental biology 13 18514643
2008 Retinoic acid-induced inner ear teratogenesis caused by defective Fgf3/Fgf10-dependent Dlx5 signaling. Birth defects research. Part B, Developmental and reproductive toxicology 12 18412219
2000 Progression in MCF-7 breast cancer cell tumorigenicity: compared effect of FGF-3 and FGF-4. Breast cancer research and treatment 11 10845805
1998 Evaluation of the tumorigenic and angiogenic potential of human fibroblast growth factor FGF3 in nude mice. Journal of cancer research and clinical oncology 11 9645456
2013 The original family revisited after 37 years: odontoma-dysphagia syndrome is most likely caused by a microduplication of chromosome 11q13.3, including the FGF3 and FGF4 genes. Clinical oral investigations 10 22297612
2012 A novel method for retinoic acid administration reveals differential and dose-dependent downregulation of Fgf3 in the developing inner ear and anterior CNS. Developmental dynamics : an official publication of the American Association of Anatomists 10 22334445
2023 Identification of a homozygous frameshift mutation in the FGF3 gene in a consanguineous Iranian family: First report of labyrinthine aplasia, microtia, and microdontia syndrome in Iran and literature review. Molecular genetics & genomic medicine 9 36934406
2002 GATA-4 interacts distinctively with negative and positive regulatory elements in the Fgf-3 promoter. Nucleic acids research 9 11842118
2021 FGF3 from the Hypothalamus Regulates the Guidance of Thalamocortical Axons. Developmental neuroscience 8 33684917
2016 Fgf3-Fgf4-cis: A new mouse line for studying Fgf functions during mouse development. Genesis (New York, N.Y. : 2000) 8 26666435
2014 Studies of genes involved in craniofacial development and tumorigenesis: FGF3 contributes to isolated oral clefts and may interact with PAX9. Acta odontologica Scandinavica 8 24697712
2023 FGF3 Directs the Pathfinding of Prethalamic GABAergic Axons. International journal of molecular sciences 6 37834446
2019 Fgf3 is crucial for the generation of monoaminergic cerebrospinal fluid contacting cells in zebrafish. Biology open 6 31036752
2016 FGF2, FGF3 and FGF4 expression pattern during molars odontogenesis in Didelphis albiventris. Acta histochemica 6 28012573
2024 Vagal sensory neuron-derived FGF3 controls insulin secretion. Developmental cell 5 39413782
1997 Identification of a MMTV insertion mutation within the coding region of the Fgf-3 protooncogene. Virology 5 9375020
2023 Fibroblast growth factor 3 promotes spontaneous mammary tumorigenesis in Tientsin albino 2 mice via the FGF3/FGFR1/STAT3 pathway. Frontiers in oncology 4 37496658
2021 Inactivation of Fgf3 and Fgf4 within the Fgf3/Fgf4/Fgf15 gene cluster reveals their redundant requirement for mouse inner ear induction and embryonic survival. Developmental dynamics : an official publication of the American Association of Anatomists 4 34719815
2019 Polymorphisms in FGF3, FGF10, and FGF13 May Contribute to the Presence of Temporomandibular Disorders in Patients Who Required Orthognathic Surgery. The Journal of craniofacial surgery 4 31574782
2014 Predicting responsiveness to sorafenib: can the determination of FGF3/FGF4 amplifications enrich for clinical benefit? Hepatobiliary surgery and nutrition 4 25202691
2012 Ectopic expression of Fgf3 leads to aberrant lineage segregation in the mouse parthenote preimplantation embryos. Developmental dynamics : an official publication of the American Association of Anatomists 4 22930543
2023 Primer on FGF3. Differentiation; research in biological diversity 3 37741710
2002 FGF3 attached to a phosholipid membrane anchor gains a high transforming capacity. Implications of microdomains for FGF3 cell transformation. The Journal of biological chemistry 3 12084721
1994 The effect of fgf-3 int-2 on growth and transformation of mcf-10a normal human mammary epithelial-cells is distinct from fgf-1 and fgf-2. International journal of oncology 3 21567063
2024 Neuroanatomical anomalies due to a defect in the FGF3 gene, associated with the Labyrinthine Aplasia, Microtia and Microdontia syndrome: insights from the placement of auditory brainstem implants in two siblings. Therapeutic advances in rare disease 2 39483301
1999 Sequence analysis of the transcription control region upstream of the human FGF-3 gene. DNA sequence : the journal of DNA sequencing and mapping 2 10727086
1994 Cooperation between mutant p53 and the ras, raf, erbb-2 and fgf-3 oncogenes for transformation of mammary epithelial-cells. International journal of oncology 1 21559693
2025 Single-Gene Deletion of FGF3 in a Patient With Features of 11q13 Microdeletion Syndrome. American journal of medical genetics. Part A 0 39976283

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