FGF8
Available structures PDB Ortholog search:PDBeRCSB List of PDB id codes 2FDB
Identifiers
Aliases	FGF8, AIGF, FGF-8, HBGF-8, HH6, KAL6, fibroblast growth factor 8
External IDs	OMIM:600483;MGI:99604;HomoloGene:7715;GeneCards:FGF8;OMA:FGF8 - orthologs
Gene location (Human) Chr. Chromosome 10 (human)[1] Band 10q24.32 Start 101,770,109bp[1] End 101,780,371bp[1]
Gene location (Mouse) Chr. Chromosome 19 (mouse)[2] Band 19 C3|19 38.75 cM Start 45,725,237bp[2] End 45,731,354bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gonad sural nerve Brodmann area 9 monocyte cingulate gyrus anterior cingulate cortex prefrontal cortex right frontal lobe tendon primary visual cortex Top expressed in surface ectoderm Apical ectodermal ridge footplate third ventricle medial nasal prominence pituitary stalk infundibular recess tail of embryo lateral nasal prominence endoderm More reference expression data BioGPS More reference expression data
Gene ontology Molecular function type 1 fibroblast growth factor receptor binding type 2 fibroblast growth factor receptor binding growth factor activity fibroblast growth factor receptor binding chemoattractant activity protein tyrosine kinase activity 1-phosphatidylinositol-3-kinase activity phosphatidylinositol-4,5-bisphosphate 3-kinase activity Cellular component extracellular region intracellular anatomical structure external side of plasma membrane extracellular space Biological process negative regulation of neuron apoptotic process cell migration involved in mesendoderm migration male genitalia development epithelial to mesenchymal transition involved in endocardial cushion formation outflow tract morphogenesis embryonic heart tube development mesonephros development heart looping forebrain neuron development blood vessel remodeling central nervous system neuron development positive regulation of ERK1 and ERK2 cascade metanephros development cell proliferation in forebrain positive regulation of mitotic nuclear division gonad development pharyngeal system development branching involved in salivary gland morphogenesis apoptotic process dopaminergic neuron differentiation cell fate commitment limb morphogenesis kidney development lung development anatomical structure morphogenesis signal transduction involved in regulation of gene expression regulation of odontogenesis of dentin-containing tooth response to oxidative stress embryo development ending in birth or egg hatching forebrain morphogenesis development of the heart telencephalon development branching involved in ureteric bud morphogenesis midbrain-hindbrain boundary development branching involved in blood vessel morphogenesis thyroid-stimulating hormone-secreting cell differentiation positive chemotaxis mesodermal cell migration cell differentiation dorsal/ventral axon guidance corticotropin hormone secreting cell differentiation organ induction neural plate morphogenesis positive regulation of organ growth negative regulation of apoptotic process BMP signaling pathway outflow tract septum morphogenesis odontogenesis thyroid gland development pallium development gastrulation canonical Wnt signaling pathway subpallium development lung morphogenesis response to organic cyclic compound otic vesicle formation forebrain dorsal/ventral pattern formation heart morphogenesis aorta morphogenesis generation of neurons MAPK cascade neuroepithelial cell differentiation multicellular organism development fibroblast growth factor receptor signaling pathway positive regulation of gene expression negative regulation of cardiac muscle tissue development determination of left/right symmetry inner ear morphogenesis positive regulation of cell population proliferation bone development motor neuron axon guidance positive regulation of cell division embryonic hindlimb morphogenesis phosphatidylinositol phosphate biosynthetic process phosphatidylinositol-3-phosphate biosynthetic process peptidyl-tyrosine phosphorylation positive regulation of cell differentiation regulation of signaling receptor activity positive regulation of protein kinase B signaling positive regulation of G protein-coupled receptor signaling pathway positive regulation of peptidyl-tyrosine phosphorylation Sources:Amigo /QuickGO
Orthologs Species Human Mouse Entrez 2253 14179 Ensembl ENSG00000107831 ENSMUSG00000025219 UniProt P55075 P37237 RefSeq (mRNA) NM_001206389 NM_006119 NM_033163 NM_033164 NM_033165 NM_001166361 NM_001166362 NM_001166363 NM_010205 NM_001379139 NM_001379140 RefSeq (protein) NP_001193318 NP_006110 NP_149353 NP_149354 NP_149355 NP_001159833 NP_001159834 NP_001159835 NP_034335 NP_001366068 NP_001366069 NP_001390029 Location (UCSC) Chr 10: 101.77 – 101.78 Mb Chr 19: 45.73 – 45.73 Mb PubMed search [3] [4]
Wikidata
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Fibroblast growth factor 8(FGF-8) is aprotein that in humans is encoded by theFGF8gene.^[5][6][7]

The protein encoded by this gene belongs to thefibroblast growth factor (FGF) family. FGF proteins are multifunctional signaling molecules with broadmitogenic and cell survival activity, playing critical roles in embryonic development, cell proliferation,morphogenesis, tissue repair, and tumor progression.^[8] FGF8 signals primarily throughfibroblast growth factor receptor 1 (FGFR1) to trigger downstream pathways involved in neural and limb development.^[9]

FGF8 is essential for establishing themidbrain–hindbrain boundary (mesencephalon/metencephalon), a key signaling center during brain development. This region is defined by cross-repression betweenOtx2 andGbx2, which helps maintain FGF8 expression. FGF8 then induces the expression of transcription factors, forming feedback loops that guide the development of themidbrain andhindbrain.^[10][11]

In theforebrain, FGF8 helps define cortical areas by regulating transcription factors such asEmx2,Pax6,COUP-TF1, andCOUP-TF2. These factors are expressed in opposing gradients and interact to establish the anterior–posterior patterning of the cerebral cortex.^[12][13]

FGF8 plays a pivotal role in early embryonic patterning, influencing the development of all three germ layers. In themesoderm, FGF8 helps regulatesomite formation through theClock and wavefront model, promoting segmentation and the establishment of anterior–posterior identity.^[14][15]

In theendoderm, FGF8 acts in coordination withretinoic acid (RA) to direct organ specification. Low levels of FGF8 promote the formation of anterior endodermal derivatives such as the liver and pancreas,^[16] while higher levels specify posterior structures such as the hindgut.^[17]

FGF8 is secreted by theapical ectodermal ridge (AER) at the distal end of limb buds and is essential for limb initiation, patterning, and outgrowth.^[18] Loss of FGF8 results in limb reduction or absence, with forelimbs and proximal segments being most affected.^[19] FGF8 also influencesSonic hedgehog (Shh) signaling and is involved in tendon and digit formation.^[20][21]

FGF8 also contributes to craniofacial development, including the formation of the teeth, palate, mandible, and salivary glands. Altered expression can result in craniofacial abnormalities such as cleft palate, mandibular hypoplasia, or tooth agenesis.^[22] In conclusion, FGF8 expression has effects on a person’s facial appearance, brain, lungs,heart, kidneys, and limbs. If there is not enough FGF8 or too much, there can be defects in all ofthese systems like limb loss, cleft lip/ palate, kidney disease, and neurodevelopmental defects.

This protein is known to be a factor that supportsandrogen and anchorage independent growth of mammary tumor cells. Overexpression of this gene has been shown to increase tumor growth andangiogenesis. The adult expression of this gene was once thought to be restricted totestes andovaries but has been described in several organ systems.^[23] Temporal and spatial pattern of this gene expression suggests its function as an embryonic epithelial factor. Studies of the mouse and chick homologs reveal roles in midbrain and limb development,organogenesis, embryogastrulation and left-right axis determination. The alternative splicing of this gene results in four transcript variants.^[24]

FGF8 has been documented to play a role in oralmaxillogacial diseases and CRISPR-cas9 gene targeting on FGF8 may be key in treating these diseases. Cleft lip and/or palate (CLP) genome wide gene analysis shows a D73H missense mutation in the FGF8 gene^[22] which reduces the binding affinity of FGF8. Loss ofTBX1 and Tfap2 can result in proliferation and apoptosis in the palate cells increasing the risk of CLP. Overexpression of FGF8 due to misregulation of the Gli processing gene may result in cliliopathies. Agnathia, a malformation of the mandible, is often a lethal condition that comes from the absence ofBMP4 regulators (noggin and chordin), resulting in high levels of BMP4 signaling, which in turn drastically reduces FGF8 signaling, increasing cell death during mandibular outgrowth.^[22] Lastly, the ability for FGF8 to regulate cell proliferation has caused interest in its effects on tumors or squamous cell carcinoma. CRISPR-cas9 gene targeting methods are currently being studied to determine if they are the key to solving FGF8 mutations associated with oral diseases.

FGF-8 knockout models have led to lethality in gastrulating state embryos in mice models.^[25] Research has demonstrated that decreased expression of FGF-8 can alter the cleft lip pathology in mice.^[26] However, due to the importance that FGF-8 has in the development and programming in multiple organ systems, full "knockout" models have led to embryonic death in multiple studies, limiting the ability to study the removal of the morphogen in adult models.^[27] While knockout experiments have occurred with this gene, a lack of/mutation in FGF8 in the early stages of embryo development is lethal. Disruption of the gene in later developmental stages has caused several issues with limb formation and development. Researchers hope to determine a way to study the signaling molecule in the future to investigate how to prevent defects includingKallmann syndrome.

• GeneReviews/NCBI/NIH/UW entry on Kallmann syndrome
• FGF8 human gene location in theUCSC Genome Browser.
• FGF8 human gene details in theUCSC Genome Browser.

• Genes on human chromosome 10

• Articles with short description
• Short description matches Wikidata