Affinage

FGF10

Fibroblast growth factor 10 · UniProt O15520

Length
208 aa
Mass
23.4 kDa
Annotated
2026-04-28
100 papers in source corpus 48 papers cited in narrative 48 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FGF10 is a secreted paracrine fibroblast growth factor that acts as a master mesenchymal-to-epithelial signal governing organ induction, branching morphogenesis, and progenitor cell maintenance across dozens of tissues including limb, lung, kidney, pancreas, salivary gland, tooth, palate, heart, and brain. It signals primarily through FGFR2b in a ternary complex with heparan sulfate proteoglycans—where specific 2-O- and 6-O-sulfation patterns determine signaling output—to activate MAPK/ERK and PI3K/Akt cascades that drive epithelial proliferation, chemotaxis, and survival while preventing premature differentiation, in part by engaging Notch and β-catenin pathways downstream (PMID:9428423, PMID:9916808, PMID:18230614, PMID:14651921, PMID:23924632). Negative feedback is mediated by Sprouty2 induction, BMP4 antagonism, and Hippo/Yap signaling, while transcription of FGF10 itself is positively regulated by ISL1/GATA4/TBX20 and negatively regulated by NF-κB/SP3 (PMID:12225946, PMID:10821767, PMID:30651296, PMID:22303449, PMID:23558680). Loss-of-function mutations in FGF10 cause LADD (lacrimo-auriculo-dento-digital) syndrome through haploinsufficiency (PMID:17682060).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1997 High

    The identity of the mesenchymal signal that directs lung epithelial budding and limb initiation was unknown; FGF10 was shown to induce directional bud outgrowth of isolated lung endoderm and ectopic limb formation with FGF8 induction in chick flank, establishing it as the key mesenchymal morphogen for these organs.

    Evidence Matrigel culture of embryonic lung endoderm with recombinant FGF10 showing budding; ectopic FGF10 bead application in chick embryo inducing complete limb with Fgf8 induction

    PMID:9187149 PMID:9428423

    Open questions at the time
    • Downstream transcriptional targets in responding epithelia not yet identified
    • Whether FGF10 acts as a chemoattractant versus a proliferative signal was unresolved
    • Receptor specificity not yet genetically established
  2. 1999 High

    Whether FGF10 was strictly required or merely sufficient for limb and lung development was unresolved; Fgf10-null mice demonstrated absolute requirement, with complete limb truncation and lung agenesis, confirming FGF10 as a non-redundant developmental regulator.

    Evidence Fgf10 knockout mouse phenotyping with histology and marker gene analysis

    PMID:9916808

    Open questions at the time
    • Mechanism of FGF10 action at the signaling level not addressed
    • Redundancy with other FGF ligands in other organs unclear
  3. 2000 High

    The receptor through which FGF10 acts in vivo and the breadth of organs affected were not genetically established; phenocopy of FGFR2b-null mice by Fgf10-null mice across thyroid, pituitary, salivary glands, teeth, kidneys, and other organs confirmed FGFR2b as the primary receptor, while BMP4 was identified as an antagonist of FGF10 signaling during lung branching.

    Evidence Fgf10-null versus Fgfr2b-null phenotypic comparison; FGF10-loaded bead cultures with BMP4/Noggin in lung endoderm Matrigel assays

    PMID:10821755 PMID:10821767 PMID:11062007

    Open questions at the time
    • Whether BMP4 acts directly on FGF10 signaling or indirectly through epithelial differentiation was unclear
    • Co-receptor requirements (heparan sulfate) not yet addressed genetically
  4. 2002 High

    The intracellular signaling pathway downstream of FGF10 and its negative feedback regulation were undefined; Sprouty2 was identified as an FGF10-induced negative regulator that suppresses MAPK by altering GRB2/RAF associations, while FGF10 was shown to protect cells via the Grb2-SOS/Ras/RAF/ERK cascade and to serve as a survival factor for dental stem cells.

    Evidence Co-IP and phosphorylation assays in MLE15 cells; dominant-negative Ras/Raf in alveolar cells; anti-FGF10 antibody neutralization and rescue in dental organ culture

    PMID:11880361 PMID:12225946 PMID:12533312

    Open questions at the time
    • PI3K/Akt arm not yet characterized
    • Whether Sprouty2 regulation operates in all FGF10-responsive tissues unknown
  5. 2003 High

    How FGF10 prevents progenitor differentiation at the molecular level was unknown; FGF10 was shown to maintain pancreatic progenitors by activating Notch signaling (Notch1/2, Hes1), with gamma-secretase inhibition abolishing FGF10's anti-differentiation effect, while heparan sulfate O-sulfation patterns were found to control the spatial response to FGF10 in lung.

    Evidence Fgf10-null and overexpressing transgenic pancreas; gamma-secretase inhibitor in pancreatic explants; selectively sulfated heparin treatment of embryonic lung cultures

    PMID:12781692 PMID:14517990 PMID:14651921

    Open questions at the time
    • Whether Notch activation is direct or indirect downstream of FGFR2b signaling unknown
    • Structural basis of HS sulfation selectivity for FGF10 not resolved
  6. 2005 High

    The genetic requirement for heparan sulfate proteoglycans in FGF10 signaling was not established in vivo; zebrafish ext2/extl3 mutants demonstrated that HSPG synthesis is specifically required for FGF10 but not FGF4 signaling during limb development.

    Evidence Positional cloning of zebrafish daedalus (fgf10) mutant; genetic interaction with ext2/extl3; differential rescue by FGF10 versus FGF4

    PMID:16221725

    Open questions at the time
    • Specific HS chain features required for FGF10 versus FGF4 selectivity not defined at structural level
    • Whether this selectivity extends to mammalian systems not tested
  7. 2006 High

    The genetic basis of LADD syndrome was linked to FGF10, and the mechanism was unknown; functional characterization of three LADD-associated FGF10 mutations revealed distinct loss-of-function mechanisms, establishing haploinsufficiency as the disease mechanism.

    Evidence Cell-based biological activity assays of FGF10 LADD mutant proteins

    PMID:17682060

    Open questions at the time
    • Genotype-phenotype correlation across LADD families not fully resolved
    • Whether modifier loci modulate LADD severity unknown
  8. 2008 High

    How HS sulfation patterns specify distinct morphogenetic outcomes downstream of FGF10 was unclear; defined heparin decasaccharides showed that 2-O-sulfation drives end bud expansion via FGFR1b while 6-O-sulfation drives duct elongation, and heparanase was shown to release FGF10-FGFR2b complexes from perlecan to increase signaling.

    Evidence BaF3/FGFR2b cell proliferation assays with defined HS decasaccharide libraries; SPR analysis of FGF10-FGFR2b-perlecan interactions; ex vivo SMG culture with heparanase

    PMID:17959718 PMID:18230614

    Open questions at the time
    • In vivo validation of HS structure-specific morphogenetic switching not achieved
    • Crystal structure of ternary FGF10-FGFR2b-HS complex with defined sulfation not available
  9. 2012 High

    How FGF10 transcription is regulated in specific organ contexts was unresolved; ISL1 was shown to directly bind a conserved FGF10 intronic enhancer, cooperating with GATA4 and TBX20, while NF-κB/RELA-SP3 co-occupancy of the Fgf10 promoter was identified as an inflammation-driven repressive mechanism.

    Evidence ChIP and EMSA for ISL1 at FGF10 enhancer; transgenic enhancer reporter mice; ChIP of LPS-treated mesenchymal cells showing RELA-SP3 promoter occupancy

    PMID:22303449 PMID:23558680

    Open questions at the time
    • Whether ISL1 regulation operates in non-cardiac tissues unknown
    • Epigenetic regulation of FGF10 locus not addressed
  10. 2017 High

    How FGF10 signaling integrates with Hippo pathway and stem cell niche regulation during homeostasis and regeneration was unknown; Hippo/Yap was shown to restrain β-catenin/FGF10 signaling for epithelial lineage commitment, while injury-induced Wnt7b from epithelium induces FGF10 in airway smooth muscle cells to expand the basal stem cell niche.

    Evidence Conditional Hippo/Yap manipulation in lung epithelium; Wnt7b gain/loss-of-function in airway injury models; Fgf10 expression analysis in ASMCs

    PMID:29017029 PMID:30651296

    Open questions at the time
    • Whether this Wnt7b-FGF10 circuit operates in other epithelial stem cell niches unknown
    • Direct Wnt7b transcriptional regulation of Fgf10 promoter not demonstrated
  11. 2020 High

    Whether FGF10-FGFR2b and other FGF-FGFR pairs activate the same downstream pathways in lung was unresolved; receptor-specific conditional knockouts revealed that FGF10-FGFR2b signals primarily through MAPK to promote proliferation and differentiation, while FGF9-FGFR3 preferentially activates PI3K, demonstrating ligand-receptor pair-specific pathway utilization.

    Evidence Receptor-specific conditional knockouts with downstream PI3K and MAPK pathway analysis in lung epithelium

    PMID:32127497

    Open questions at the time
    • Whether pathway preference is cell-type-specific or universal to all FGF10-responsive epithelia unknown
    • Quantitative contribution of each pathway to specific cellular outcomes not determined
  12. 2022 High

    FGF10 was assumed to be exclusively mesenchymal; single-cell RNA-seq and lineage tracing revealed a postnatal switch to epithelial FGF10 expression in salivary gland ductal ionocytes expressing Foxi1/Ascl3/Cftr, revealing a previously unrecognized autocrine/paracrine role in gland homeostasis.

    Evidence Single-cell RNA sequencing atlas; Fgf10CreERT2 lineage tracing; RNA-seq of sorted FGF10+ epithelial populations

    PMID:35417692

    Open questions at the time
    • Functional consequence of epithelial FGF10 loss in adult gland homeostasis not tested by conditional deletion
    • Whether epithelial FGF10 expression occurs in other adult organs unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of the FGF10-FGFR2b-HS ternary complex with defined sulfation patterns, the full spectrum of direct transcriptional targets across different responding epithelia, and whether the developmental FGF10 signaling logic is recapitulated in adult tissue regeneration and cancer progression.
  • No high-resolution structure of FGF10-FGFR2b-HS ternary complex with defined sulfation
  • Comprehensive ChIP-seq for FGF10 downstream effectors across tissues lacking
  • Role in adult tissue homeostasis beyond lung basal cells and salivary gland ionocytes not systematically addressed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 5 GO:0008289 lipid binding 4
Localization
GO:0005576 extracellular region 4 GO:0031012 extracellular matrix 1
Pathway
R-HSA-1266738 Developmental Biology 7 R-HSA-162582 Signal Transduction 5 R-HSA-1500931 Cell-Cell communication 3
Partners
BMP4FGFBP1FGFR2GATA4ISL1SPRY2TBX20

Evidence

Reading pass · 48 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 FGF10 is essential for limb bud outgrowth and pulmonary branching morphogenesis; Fgf10-null mice lack lungs and have complete limb truncation, with failure to form the apical ectodermal ridge (AER) and zone of polarizing activity (ZPA), establishing FGF10 as a required mesenchymal regulator of these structures. Fgf10 knockout mice, histology, marker gene expression analysis Nature genetics High 9916808
1997 FGF10 expressed in the distal lung mesenchyme acts as a directional cue inducing epithelial bud outgrowth and proliferation; isolated lung endoderm in Matrigel treated with FGF10 undergoes budding (unlike FGF7), demonstrating a unique morphogenetic activity. In vitro Matrigel and collagen gel culture of embryonic lung endoderm with recombinant FGF proteins, transgenic Shh overexpression showing Fgf10 downregulation Development (Cambridge, England) High 9428423
1997 FGF10 from the prospective limb mesenchyme induces Fgf8 expression in the adjacent ectoderm and can induce formation of an additional complete limb when applied ectopically, establishing FGF10 as the mesenchymal initiator of limb bud formation upstream of FGF8. Ectopic FGF10 application in chick embryo flank, in situ hybridization for Fgf8 and Sonic hedgehog Development (Cambridge, England) High 9187149
2000 FGF10 acts as the major ligand for FGFR2b in multi-organ development; Fgf10-null mice phenocopy FGFR2b-null mice with agenesis of thyroid, pituitary, salivary glands, and defects in teeth, kidneys, hair follicles, and digestive organs. Fgf10 knockout mouse phenotypic analysis, comparison to Fgfr2b-null phenotype Biochemical and biophysical research communications High 11062007
1998 FGFR2 signaling mediates a reciprocal regulation loop between FGF8 (ectodermal) and FGF10 (mesenchymal) during limb induction; FGFR2 deletion abolishes Fgf8 expression in limb ectoderm and downregulates Fgf10 in mesoderm. FGFR2 domain-deletion knock-in mice, in situ hybridization for Fgf8 and Fgf10 Development (Cambridge, England) High 9435295
2000 FGF10 induces both chemotaxis and proliferation of isolated lung endoderm; BMP4 (expressed in distal endoderm) antagonizes FGF10-induced budding and chemotaxis, while the BMP antagonist Noggin enhances FGF10-induced morphogenesis, establishing opposing roles for FGF10 and BMP4 in branching morphogenesis. FGF10-loaded bead cultures of isolated lung endoderm in Matrigel, exogenous BMP4 and Noggin addition, Bmp4-lacZ reporter mice Development (Cambridge, England) High 10821767
2004 Mesenchymal FGF10 regulates epithelial expression of Sonic hedgehog (Shh) in palate development; Shh is a downstream target of Fgf10/Fgfr2b signaling and signals back to the mesenchyme to promote cell proliferation in both compartments. Fgf10-/-, Fgfr2b-/-, and Shh mutant mouse analysis; cell proliferation assays (BrdU) in palatal epithelium and mesenchyme The Journal of clinical investigation High 15199404
2003 FGF3 and FGF10 act redundantly as signals required for otic placode induction; embryos lacking both Fgf3 and Fgf10 fail to form otic vesicles with aberrant otic marker gene expression, while single mutants show less severe defects. Fgf3/Fgf10 double knockout mice, in situ hybridization for otic markers, cell proliferation and survival assays Development (Cambridge, England) High 12810586
2002 FGF10/FGFR2b signaling is required for mammary placode development (placodes 1, 2, 3, and 5) but not placode 4, identifying two distinct signaling pathways during mammary gland formation. Fgf10-/- and Fgfr2b-/- mouse analysis with Lef1 as epithelial marker Development (Cambridge, England) High 11782400
2003 FGF10 maintains pancreatic progenitor cell proliferation and prevents their differentiation; ectopic FGF10 in transgenic pancreas activates Notch1, Notch2, Jagged1, Jagged2, and Hes1, indicating FGF10 signals through Notch to block differentiation of progenitors. Fgf10 null and FGF10-overexpressing transgenic mice, marker expression (Pdx1, Nkx6.1, Notch pathway genes), proliferation assays Developmental biology High 14651921
2003 FGF10 maintains Notch activation in pancreatic progenitors; gamma-secretase inhibitor suppression of Notch (Hes1 downregulation) abolishes FGF10's ability to sustain progenitor proliferation and block differentiation in pancreatic explant cultures. Dorsal pancreatic epithelium explant culture with FGF10, gamma-secretase inhibitor treatment, Notch target gene expression analysis Developmental dynamics High 14517990
2007 FGF10 signaling from adjacent mesenchyme is required to maintain hepatopancreatic ductal identity; in zebrafish fgf10 mutants, ductal epithelial cells misdifferentiate toward hepatic and pancreatic fates, showing FGF10 prevents organ-specific differentiation of ductal progenitors. Zebrafish fgf10 mutant analysis, marker gene expression, cell fate analysis Nature genetics High 17259985
2009 Fgf10 regulates the timing of neuroepithelial cell (NC) to radial glia (RG) differentiation in the cortex; Fgf10 deletion delays RG differentiation selectively in rostral cortex causing extended symmetric NC divisions, while overexpression has opposing effects, ultimately determining cortical area size and laminar thickness. Fgf10 knockout and overexpression mice, BrdU lineage tracing, cortical progenitor marker analysis Neuron High 19607792
2002 FGF10 is a survival factor for the dental epithelial stem cell compartment (cervical loop) in developing mouse incisors; neutralizing anti-FGF10 antibody induces apoptosis in the cervical loop, and recombinant FGF10 rescues it from apoptosis. Fgf10-null mouse incisor analysis, organ culture with neutralizing antibody and recombinant FGF10, TUNEL assay Development (Cambridge, England) High 11880361
2000 FGF10 is sufficient to stimulate ectopic lacrimal bud formation; Pax6 is a competence factor required for the epithelium to respond to FGF10; inhibition of FGFR2-IIIb suppresses endogenous lacrimal bud development, and FGF10 in mesenchyme-free gland epithelium stimulates growth but not branching. Ocular explant culture with recombinant FGF10, Pax6 mutant analysis, FGFR2-IIIb inhibition, Fgf10-null mouse phenotype Development (Cambridge, England) High 10821755
2002 Tbx5 functions upstream of Wnt2b to regulate Fgf10 expression during limb initiation; Fgf10 in turn maintains Tbx5 expression during limb outgrowth, establishing a Tbx5-Wnt2b-Fgf10 feedback loop for forelimb specification. Zebrafish and chick gain- and loss-of-function experiments, epistasis analysis of Tbx5/Wnt/Fgf pathway interactions Development (Cambridge, England) High 12399308
2005 Heparan sulfate proteoglycans (HSPGs) synthesized by Ext2 and Extl3 are specifically required for FGF10 (but not FGF4) signaling during zebrafish limb development; genetic interaction between fgf10 and extl3 mutants, and FGF10 protein rescues target gene activation in fgf10 but not ext2/extl3 mutants. Zebrafish fgf10 (daedalus) mutant positional cloning, genetic interaction with ext2/extl3 mutants, exogenous FGF10/FGF4 protein rescue assays Development (Cambridge, England) High 16221725
2007 Heparanase cleaves perlecan heparan sulfate to release FGF10 and FGF10-FGFR2b complexes from the basement membrane ECM, increasing MAPK signaling, epithelial clefting, and lateral branch formation during submandibular gland branching morphogenesis. Ex vivo SMG culture with heparanase inhibition/addition, solid-phase binding assay, surface plasmon resonance (SPR) analysis of FGF10-FGFR2b-perlecan interactions, FGF10-FGFR2b complex as HS probe Development (Cambridge, England) High 17959718
2003 Specific O-sulfation patterns of heparan sulfate modulate FGF10 signaling in the lung; O-sulfated groups are critical for FGF10 signaling activation in epithelium during lung bud formation, and regionally distributed HS sulfation patterns determine the spatial response to FGF10. Embryonic lung culture with selectively sulfated heparins, disruption of endogenous HS gradients, gene expression analysis Developmental biology High 12781692
2008 Specific heparan sulfate structures with 2-O- and 6-O-sulfation form a ternary signaling complex (FGF10·FGFR2b·HS) and modulate distinct FGF10-mediated outcomes in submandibular gland epithelia: 2-O-sulfation drives end bud expansion via FGFR1b, while 6-O-sulfation alone drives duct elongation. BaF3/FGFR2b cell proliferation assay with defined heparin decasaccharide libraries, primary SMG epithelia morphogenesis assays, receptor and marker gene expression analysis The Journal of biological chemistry High 18230614
2005 FGF10 in the palatal mesenchyme is required for MEE cell survival and normal expression of Jagged2 and Tgfbeta3 in the palatal epithelium; Fgf10 is epistatic to Jagged2 and Tgfbeta3 during palatogenesis. Fgf10-null mouse analysis, TUNEL and BrdU assays, in situ hybridization for Jagged2 and Tgfbeta3 Developmental biology High 15572143
2002 mSprouty2 (mSpry2) is induced by FGF10 in lung epithelium and negatively regulates FGF10-activated MAP kinase signaling; FGF10 stimulation causes mSpry2 tyrosine phosphorylation, increased association with GRB2, SH2B2, and RAF, and decreased binding to PTP2 and GAP1, resulting in net MAPK suppression. MLE15 cell overexpression of mSpry2, co-immunoprecipitation, phosphorylation assays, subcellular localization imaging after FGF10 stimulation American journal of physiology. Lung cellular and molecular physiology High 12225946
2004 FGF10 targets in lung epithelium include genes associated with cell rearrangement, migration, and lipid metabolism (not cell proliferation) at initial budding stages; FGF10 also induces genes implicated in tumor invasion/metastasis in multiple developing organs. Gene expression profiling of lung epithelial explants treated with FGF10 in absence of mesenchyme; validation by in situ hybridization and local FGF10 bead application in intact lungs The Journal of biological chemistry High 15556938
2006 Cessation of FGF10 signaling in the dental stem cell compartment causes transition from crown to root formation; continuous FGF10 maintains the apical bud/stem cell compartment, and forced FGF10 overexpression during the crown-to-root transition inhibits Hertwig's epithelial root sheath formation. Fgf10-null incisor transplantation under kidney capsule, BrdU labeling, CK14/Notch2 immunostaining, FGF10 overexpression in transitional molar germs Development (Cambridge, England) High 16510502
2011 FGF10/FGFR2b signaling from the myocardium to epicardium is essential for cardiac fibroblast migration into the compact myocardium; inactivation reduces epicardial-derived cells in the myocardium, decreases myocardial proliferation, and produces a smaller thin-walled heart. Fgf10/Fgfr2b conditional knockout mice, lineage tracing of epicardial-derived cells, myocardial proliferation assays Development (Cambridge, England) High 21750042
2009 In the absence of GDNF and Spry1, kidney development requires FGF10 for ureteric bud branching; removing even one Fgf10 allele in Gdnf-/-;Spry1-/- double mutants causes complete failure of ureter and kidney development, demonstrating FGF10 can substitute for GDNF/RET signaling when negative regulation is relieved. Triple and quadruple knockout mouse genetics (Gdnf, Spry1, Fgf10), renal morphology analysis PLoS genetics High 20084103
2006 LADD syndrome mutations in FGF10 are loss-of-function; three different FGF10 LADD mutants have severely impaired biological activity by distinct mechanisms, and haploinsufficiency of FGF10 causes LADD syndrome. Functional assays of FGF10 LADD mutant proteins in cell-based biological activity assays Molecular and cellular biology High 17682060
2005 FGF-binding protein (FGF-BP) is a novel interaction partner of FGF-10 (as well as FGF-7 and FGF-22) and enhances the activity of low concentrations of these ligands; FGF-BP expression increases after skin injury, potentially amplifying FGF10 activity at wound sites. Co-precipitation/binding assays demonstrating FGF-BP interaction with FGF-10, activity enhancement assays, wound expression analysis Oncogene Medium 15806171
2011 2-O- and 6-O-sulfation of heparan sulfate are required for Fgf10-Fgfr2b signaling during lacrimal gland development; combined Hs2st;Hs6st deletion abolishes lacrimal gland development, disrupts Fgf10-Fgfr2b-HS ternary complex formation on cell surface, prevents Fgf10-induced lacrimal bud induction, and abrogates ERK signaling downstream of FGF10. Conditional knockout of Hs2st, Hs6st1, Hs6st2 in lacrimal gland; phage display antibodies for HS structure; genetic interaction with Fgf10; explant induction assays; ERK signaling analysis The Journal of biological chemistry High 21357686
2013 Localized Fgf10 expression is not required for branching morphogenesis per se; ubiquitous FGF10 overexpression rescues lung agenesis in Fgf10 knockout mice. FGF10 prevents differentiation of distal epithelial progenitors into Sox2-expressing airway cells by activating epithelial β-catenin signaling, which negatively regulates Sox2; once cells commit to Sox2+ airway fate, FGF10 prevents ciliated cell differentiation and promotes basal cell differentiation. Fgf10 knockout rescue with ubiquitous Fgf10 overexpression; Dkk1 co-overexpression epistasis; β-catenin signaling analysis in epithelium; Sox2 expression analysis Development (Cambridge, England) High 23924632
2017 During lung homeostasis, basal stem cells (BSCs) maintain stemness by downregulating Hippo signaling (nuclear Yap), generating an Fgf10-expressing stromal niche; after injury, epithelial-derived Wnt7b induces Fgf10 expression in airway smooth muscle cells (ASMCs) to extend the BSC niche for regeneration. Conditional Hippo pathway manipulation, Wnt7b gain/loss-of-function, Fgf10 expression analysis in ASMCs, airway injury models, live imaging/fractionation Developmental cell High 29017029
2017 FGF10 exerts neuroprotection after spinal cord injury via FGFR2/PI3K/Akt signaling (reducing apoptosis and repairing neurites) and inhibits microglia/macrophage activation and pro-inflammatory cytokine release through TLR4/NF-κB pathway suppression; siRNA knockdown of FGFR2 abolishes FGF10's anti-apoptotic effects in vitro. Mouse SCI model with exogenous FGF10; PI3K inhibitor (LY294002) and FGFR2 siRNA knockdown; NF-κB and PI3K/Akt pathway analysis Cell death & disease Medium 28981091
2016 FGF10 ameliorates cerebral ischemia injury by activating PI3K/Akt signaling (anti-apoptotic) and inhibiting NF-κB-dependent neuroinflammation; PI3K/Akt blockade partially reverses neuroprotection but does not affect anti-inflammation, indicating these are distinct downstream mechanisms. Mouse MCAO model with intraventricular FGF10; wortmannin and Akt inhibitor treatment; NF-κB and PI3K/Akt pathway analysis; TUNEL and caspase activity assays Scientific reports Medium 26813160
2003 FGF10 protects alveolar epithelial cells from cyclic stretch-induced DNA damage via MAPK activation through the Grb2-SOS/Ras/RAF-1/ERK1/2 pathway; dominant-negative RAS and RAF-1 inhibitors block FGF10-induced ERK phosphorylation and abolish protection. Cyclic stretch of AEC, FGF10 pretreatment, alkaline unwinding and DNA fragmentation assays, MAPK pathway inhibitors, dominant-negative RAS-expressing cells American journal of physiology. Lung cellular and molecular physiology High 12533312
2006 FGF10 stimulates preadipocyte proliferation in white adipose tissue through the Ras/MAPK pathway, leading to cyclin D2 expression and p130 phosphorylation; FGF10 also induces pRb expression required for adipogenesis. Fgf10-null WAT analysis, MEF cell stimulation with FGF10, Ras/MAPK inhibitor, cyclin D2 and p130/pRb analysis Molecular and cellular endocrinology High 16513252
2012 ISL1 directly binds to a conserved intronic enhancer element of FGF10 to regulate its transcription in the cardiac outflow tract; GATA4 and TBX20 cooperate with ISL1 to enhance FGF10 transcription from this element. ChIP and EMSA demonstrating ISL1 occupancy of FGF10 intronic enhancer; transgenic mice with human FGF10 enhancer reporter; luciferase reporter assays with GATA4 and TBX20 co-expression PloS one High 22303449
2013 NF-κB activation suppresses FGF10 expression via RELA-SP3 interactions at the Fgf10 promoter; RELA subunit and SP3 co-occupy the Fgf10 promoter upon LPS treatment and suppress SP1-mediated transcription, linking inflammation to reduced FGF10 during lung development. Fgf10 promoter luciferase assays, ChIP of LPS-treated fetal lung mesenchymal cells, constitutively active IKKβ and dominant-negative IκB overexpression The Journal of biological chemistry High 23558680
2017 miR-327 targets FGF10 to prevent beige adipocyte differentiation; β-adrenergic stimulation upregulates FGF10 which acts through FGFR2 in an autocrine loop to promote preadipocyte differentiation into beige adipocytes; systemic miR-327 inhibition induces WAT browning. miRNA gain/loss-of-function experiments, local WAT miR-327 delivery, FGF10 and FGFR2 expression/signaling analysis, adipocyte differentiation assays in vivo and in vitro Nature communications High 29233981
2014 FGF10 regulates foetal right-ventricular cardiomyocyte proliferation through FOXO3/p27kip1 pathway; FGF10 and FGFR2b are expressed in cardiomyocytes (not fibroblasts), indicating cell-autonomous signaling; in vivo FGF10 overexpression in adult mice promotes cardiomyocyte but not fibroblast cell-cycle re-entry. Fgf10-null heart analysis, primary cardiomyocyte cultures, FOXO3/p27kip1 pathway analysis, cell-type-specific expression analysis, in vivo FGF10 overexpression Cardiovascular research High 25344367
2020 FGF9 and FGF10 activate distinct intracellular signaling pathways in lung epithelial cells: FGF10 signals through FGFR2b to activate primarily MAPK pathways promoting epithelial proliferation and differentiation, whereas FGF9 signals through FGFR3 to preferentially use PI3K pathways promoting distal fate specification and opposing FGF10-FGFR2b signaling. Receptor-specific conditional knockouts, ligand-receptor combination assays, downstream PI3K and MAPK pathway analysis in lung epithelium Science signaling High 32127497
2010 TGF-β signaling in cranial neural crest (CNC) cells induces Scleraxis and FGF10 expression; FGF10 in turn regulates myogenic cell proliferation and organization during tongue muscle development; exogenous FGF10 rescues muscle cell number in Tgfbr2-CNC conditional knockout mice. Wnt1-Cre;Tgfbr2 conditional knockout mice, FGF10 rescue experiment, TGF-β2 bead induction of Scleraxis in tongue explants Developmental biology High 20193675
2022 FGF10 expression switches from mesenchymal to epithelial cells in salivary glands postnatally; epithelial FGF10-positive cells express ionocyte markers (Foxi1, Foxi2, Ascl3, Cftr) and represent a specialized ductal ionocyte population that maintains gland homeostasis via FGFR2b signaling. Single-cell RNA sequencing atlas of salivary gland; inducible Fgf10CreERT2:R26-tdTomato lineage tracing; RNA-seq of sorted FGF10+ mesenchymal and epithelial populations Cell reports High 35417692
2019 Hippo signaling promotes epithelial lineage commitment by curbing Fgf10 and β-catenin signaling; both inactivation of Hippo (nuclear Yap) and ablation of Yap increase β-catenin and Fgf10 signaling, demonstrating a cytoplasmic role for Yap in regulating epithelial progenitor differentiation. Conditional Yap/Taz inactivation and Hippo pathway manipulation in lung epithelium; β-catenin and Fgf10 signaling analysis Development (Cambridge, England) High 30651296
2009 Mesodermal FGF8 and FGF10 have overlapping functions in outflow tract/right ventricle development and pharyngeal arch artery formation; compound mesodermal Fgf8;Fgf10 mutants show synergistic cardiovascular defects, demonstrating functional redundancy and FGF dosage sensitivity. MesP1Cre-mediated compound Fgf8;Fgf10 mesodermal knockouts, cardiac morphology and marker analysis Circulation research High 20035084
2008 Stromal FGF10 induces migration and invasion of pancreatic cancer cells through FGFR2-IIIb, and upregulates MT1-MMP and TGF-β1 mRNA expression while increasing TGF-β1 protein secretion from cancer cell lines. FGF10 stimulation of CFPAC-1 and AsPC-1 pancreatic cancer cell lines, migration/invasion assays, FGFR2-IIIb interaction, MT1-MMP and TGF-β1 mRNA/protein quantification British journal of cancer Medium 18594526
2009 FGF10-FGFR2b-Sprouty2 signaling pathway mediates increased branching in response to tracheal occlusion (elevated intraluminal pressure); tracheal occlusion fails to increase branching in Fgfr2b-null mice or when FGFR2b antisense is used, and is attenuated in Fgf10 hypomorphic lungs. Tracheal occlusion in wild-type, Fgfr2b-null, and Fgf10 hypomorphic lungs; RT-PCR for Fgf10, Vegf, Sprouty2, Shh; antisense Fgfr2b organ culture Mechanisms of development High 18082381
2009 FGF10 signal from pancreatic mesenchyme is required for progenitor expansion; the Fgf10-arrested progenitor state is reversible, and cell competence toward endocrine and ductal fates depends on gestational timing of Fgf10 expression; sustained Fgf10 during secondary transition causes irreversible loss of Ngn3 expression and endocrine competence. Conditional Fgf10 gain-of-function with temporal control, Ngn3 and Ptf1a expression analysis, lineage competence assays Mechanisms of development High 19969077
2017 The Dlx5-FGF10 signaling cascade regulates cranial neural crest (CNC) cell proliferation and myoblast differentiation in oropharyngeal patterning; Dlx5 loss downregulates FGF10 pathway, and activation of FGF10 signaling rescues CNC cell proliferation and myogenic differentiation in Dlx5 mutants. Dlx5 conditional knockout mice, FGF10 pathway activation rescue experiments, proliferation and apoptosis analysis in CNC and muscle progenitor cells Development (Cambridge, England) High 28982687

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Fgf10 is essential for limb and lung formation. Nature genetics 973 9916808
1997 Fibroblast growth factor 10 (FGF10) and branching morphogenesis in the embryonic mouse lung. Development (Cambridge, England) 794 9428423
2000 FGF10 acts as a major ligand for FGF receptor 2 IIIb in mouse multi-organ development. Biochemical and biophysical research communications 495 11062007
1998 Fibroblast growth factor receptor 2 (FGFR2)-mediated reciprocal regulation loop between FGF8 and FGF10 is essential for limb induction. Development (Cambridge, England) 458 9435295
1997 The mesenchymal factor, FGF10, initiates and maintains the outgrowth of the chick limb bud through interaction with FGF8, an apical ectodermal factor. Development (Cambridge, England) 446 9187149
2000 Bmp4 and Fgf10 play opposing roles during lung bud morphogenesis. Development (Cambridge, England) 398 10821767
2004 Disruption of Fgf10/Fgfr2b-coordinated epithelial-mesenchymal interactions causes cleft palate. The Journal of clinical investigation 296 15199404
2003 Fgf3 and Fgf10 are required for mouse otic placode induction. Development (Cambridge, England) 238 12810586
2002 Role of FGF10/FGFR2b signaling during mammary gland development in the mouse embryo. Development (Cambridge, England) 221 11782400
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 210 11066089
2003 Expression and function of FGF10 in mammalian inner ear development. Developmental dynamics : an official publication of the American Association of Anatomists 205 12761848
2002 FGF10 maintains stem cell compartment in developing mouse incisors. Development (Cambridge, England) 187 11880361
2002 The limb identity gene Tbx5 promotes limb initiation by interacting with Wnt2b and Fgf10. Development (Cambridge, England) 182 12399308
2000 FGF10 is an inducer and Pax6 a competence factor for lacrimal gland development. Development (Cambridge, England) 175 10821755
2003 Requirements for FGF3 and FGF10 during inner ear formation. Development (Cambridge, England) 172 14623822
2003 FGF10 signaling maintains the pancreatic progenitor cell state revealing a novel role of Notch in organ development. Developmental biology 165 14651921
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