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FLASH GENE
Symbol FGF8 contributors: mct - updated : 12-12-2018
HGNC name fibroblast growth factor 8 (androgen-induced)
HGNC id 3686
Corresponding disease
BFPH bilateral femoral and pelvic bones hypoplasia , isolated
KAL6 Kallmann syndrome
Location 10q24.32      Physical location : 103.529.886 - 103.535.759
Synonym name
  • androgen-induced growth factor
  • heparin-binding growth factor 8
  • Synonym symbol(s) AIGF, HBGF8, MGC149376, FGF-8, HBGF-8, HH6, KAL6
    DNA
    TYPE functioning gene
    STRUCTURE 5.94 kb     6 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    text structure six exons including four alternative exon 1
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 1036 27.8 244 - 2003 12778074
    also called variant F/isoform F
    5 splicing 949 24.4 215 cells (increase tumor growth) of prostatic cancer 2003 12778074
    also called variant B/isoform B
    6 splicing 1003 26.5 233 - 2003 12778074
    also called variant E/isoform E
    5 splicing 916 23.2 204 in the cardiac progenitors 2003 12778074
  • also called variant A/isoform A
  • role for FGF8A and NOTCH signaling in regulating MG (Muller glial cell) quiescence, activation, and proliferation (PMID: 28445734)
  • role for CDC42 in an FGF8A-specific signaling pathway essential for vertebrate neuronal development (PMID: 23994638)
  • 5 - 856 - 140 - 2003 12778074
    EXPRESSION
    Type restricted
    constitutive of
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrainhindbrain   
    Reproductivefemale systembreast   
     female systemovary   
     male systemtestis   
     male systemprostate   
    Urinarykidney    
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text developing brain (isthmus midbrain) letf-right (L/R) axis determination
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    HOMOLOGY
    interspecies homolog to murine Fgf8
    homolog to Drosophila FGF8
    Homologene
    FAMILY
  • fibroblast growth factors family
  • FGF8 subfamily
  • CATEGORY signaling growth factor
    SUBCELLULAR LOCALIZATION extracellular
    basic FUNCTION
  • stimulating growth of the cells in an autocrine manner
  • mediating hormonal action on the growth of cancer cells
  • FGF4 and FGF8 are the principal FGFs required for both axis extension and limb bud outgrowth
  • expression in prostate cancer cells increases their growth as intratibial tumors and modulates formation of bone lesions
  • FGF8, FGF17 and EMX2 play distinct roles in the molecular regionalization of frontal cortex subdivisions (
  • involved in gastrulation, regionalization of the brain, axial elongation and organogenesis of the limb and face
  • may participate in the degradation of cartilage and exacerbation of osteoarthritis
  • regulates myoblast differentiation through the regulation of MYOD1 expression
  • may have a physiological role in bone acting in an autocrine/paracrine manner
  • crucial role of a defined FGF8 expression pattern controlling inner ear formation in vertebrates
  • regulating the development of the thalamic motor learning area
  • FGF8 signalling is both required and sufficient to induce rostral Cajal-Retzius cells
  • in addition to its organizer function, plays a crucial role in maintaining the lineage boundary at the midbrain-hindbrain by restricting cell movement
  • GBX2 and FGF8 are sequentially required for formation of the midbrain-hindbrain compartment boundary
  • FGF4 and FGF8 action maintains WNT signaling, and that both signaling pathways are required in parallel to maintain PSM (presomitic mesoderm) progenitor tissue
  • FGF4 and FGF8 signaling acts as the sole mediator of wavefront activity
  • chemotactic and chemokinetic for cardiac neural crest
  • with FGF17, is a key factor in the patterning of the mid-hindbrain region with a complex picture of spatiotemporal gene expression during the various stages of cerebellar development
  • HTRA1 and FGF8 may function coordinately in the common FGF signaling pathway
  • FGF8 and FGF10 promotes the proliferation of the cardiac progenitor cells that form the arterial pole of the heart
  • FGF8 signaling is involved in craniofacial development
  • FGF8 receiving cells control likely both, the propagation width and the signal strength of the morphogen
  • FGF8 acts as a binary switch that distinguishes tubular elongation from lumen formation in kidney
  • regulates postnatal development of paraventricular nucleus neuroendocrine cells
  • FGF8 and FGFR3 may play an important role in the onset of deep zone necrosis and pathogenesis in osteochondropathy Kashin-Beck disease in adolescent children
  • FGF8 and SHH promote the survival and maintenance of multipotent neural crest progenitors
  • FGF8, FGF17 and FGF18 are required for closure of the embryonic ventral body wall
  • key regulator of limb development and several limb enhancer elements, and key signaling factor for embryo patterning
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
  • FOXC1 - FGF8 signaling regulates mammalian jaw patterning, providing a mechanistic basis for the pathogenesis of syngnathia
  • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • HOXA2 expression (in mouse), fibroblast growth factor tyrosine kinase receptors
  • interacting with IHH (may be playing different roles and acting synergistically to promote chondrogenesis during digit primordia elongation)
  • FGF4 and FGF8 are the critical ligands for FGF signaling in the presomitic mesoderm
  • key role of senataxin in neuronal differentiation through FGF8 signalling
  • HTRA1 directly cleaves FGF8 in the extracellular region, and this cleavage results in decreased activation of FGF signaling, which is essential for many physiological processes
  • OTX2 prevents the presumptive RPE region from forming the neural retina (NR) by repressing the expression of both FGF8 and SOX2 which induce the NR cell fate
  • FGF8, a key mediator of cell survival, migration, proliferation, and patterning in the developing head, is a high affinity ligand for CUBN
  • plasma membrane binding of FGF8, and most likely of the FGF8 family members FGF17 and FGF18, to CUBN improves Fgf ligand endocytosis and availability to FgfRs, thus modulating Fgf signaling activity
  • TBX1 coordinates the WNT-dependent epithelial destabilization of pouch-forming cells with their collective migration towards FGF8A-expressing mesodermal guideposts
  • FGF8 activates RAS-ERK pathway to specify hindbrain
  • TBX2, which is a target gene of BMP signal, down-regulates FGF8 signaling by inhibiting the expression of FLRT3, a positive regulator of this pathway
  • GMNN regulates FGF8 and NOTCH signaling to regulate somite segmentation during somitogenesis
  • CUBN-FGF8 interaction may be relevant in human pathology, including in cancer progression, heart or neural tube defects
  • cell & other
    REGULATION
    induced by by androgen
    PAX2
    repressed by RA (Retinoic acid controls body axis extension by directly repressing FGF8 transcription)
    ASSOCIATED DISORDERS
    corresponding disease(s) KAL6 , BFPH
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       gain of function
    in breast and eophageal cancers
    tumoral     --over  
    in prostate cancer
    tumoral     --over  
    in bone metastases of human prostate cancer
    constitutional germinal mutation      
    contribute to the formation of the VATER/VACTERL association
    Susceptibility to hypospadias
    Variant & Polymorphism other polymorphisms increasing the risk of hypospadias
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    right isomerism in mutant mice -/-