FGF10

FGF10
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1NUN
Identifiers
Aliases	FGF10, fibroblast growth factor 10
External IDs	OMIM: 602115; MGI: 1099809; HomoloGene: 3284; GeneCards: FGF10; OMA:FGF10 - orthologs
Gene location (Human) Chr. Chromosome 5 (human) Band 5p12 Start 44,300,247 bp End 44,389,706 bp
Gene location (Mouse) Chr. Chromosome 13 (mouse) Band 13 D2.3|13 67.14 cM Start 118,806,327 bp End 118,928,651 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in buccal mucosa cell synovial joint canal of the cervix ectocervix synovial membrane left uterine tube vagina gastric mucosa caput epididymis muscle layer of sigmoid colon Top expressed in otic pit muscle layer of seminal vesicle hair lamina propria of vagina spermatid dentate gyrus of hippocampal formation granule cell pituitary stalk zygote primordial pancreas embryo More reference expression data BioGPS n/a
Gene ontology Molecular function heparin binding type 2 fibroblast growth factor receptor binding growth factor activity protein binding 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 nucleus cell surface extracellular matrix plasma membrane extracellular space collagen-containing extracellular matrix Biological process bud outgrowth involved in lung branching limb bud formation organ growth semicircular canal morphogenesis embryonic pattern specification bud elongation involved in lung branching positive regulation of canonical Wnt signaling pathway muscle cell fate commitment tear secretion positive regulation of Ras protein signal transduction positive regulation of urothelial cell proliferation regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling limb development radial glial cell differentiation female genitalia morphogenesis mesonephros development odontogenesis of dentin-containing tooth prostatic bud formation blood vessel remodeling regulation of saliva secretion angiogenesis establishment of mitotic spindle orientation positive regulation of ERK1 and ERK2 cascade embryonic digestive tract morphogenesis animal organ morphogenesis hair follicle morphogenesis metanephros development lung saccule development lung epithelium development positive regulation of Notch signaling pathway negative regulation of cell population proliferation branch elongation involved in salivary gland morphogenesis branching involved in salivary gland morphogenesis positive regulation of white fat cell proliferation bronchiole morphogenesis limb morphogenesis blood vessel morphogenesis lung development thymus development positive regulation of fibroblast proliferation negative regulation of cell differentiation ERK1 and ERK2 cascade positive regulation of epithelial cell migration positive regulation of mitotic cell cycle spleen development smooth muscle cell differentiation positive regulation of transcription, DNA-templated positive regulation of Wnt signaling pathway Harderian gland development protein localization to cell surface respiratory system development epidermis development positive regulation of peptidyl-tyrosine phosphorylation metanephros morphogenesis pancreas development mammary gland bud formation positive chemotaxis mesenchymal-epithelial cell signaling involved in lung development positive regulation of hair follicle cell proliferation lacrimal gland development positive regulation of MAPK cascade cell differentiation positive regulation of keratinocyte proliferation positive regulation of ATP-dependent activity positive regulation of epithelial cell proliferation involved in wound healing epithelial cell differentiation organ induction positive regulation of epithelial cell proliferation epidermis morphogenesis wound healing epithelial cell proliferation regulation of activin receptor signaling pathway positive regulation of DNA replication chemotaxis embryonic genitalia morphogenesis salivary gland development positive regulation of keratinocyte migration response to lipopolysaccharide thyroid gland development keratinocyte proliferation semicircular canal fusion mammary gland specification epithelial cell migration white fat cell differentiation regulation of gene expression lung alveolus development branching morphogenesis of an epithelial tube embryonic digestive tract development lung proximal/distal axis specification fibroblast growth factor receptor signaling pathway involved in mammary gland specification actin cytoskeleton reorganization positive regulation of vascular endothelial growth factor receptor signaling pathway pituitary gland development response to estradiol secretion by lung epithelial cell involved in lung growth mesenchymal cell differentiation involved in lung development lung morphogenesis response to organic cyclic compound somatic stem cell population maintenance tissue regeneration otic vesicle formation epithelial cell proliferation involved in salivary gland morphogenesis cell-cell signaling male genitalia morphogenesis positive regulation of DNA repair salivary gland morphogenesis MAPK cascade embryonic camera-type eye development induction of positive chemotaxis urothelial cell proliferation animal organ formation fibroblast growth factor receptor signaling pathway regulation of smoothened signaling pathway determination of left/right symmetry inner ear morphogenesis positive regulation of cell population proliferation submandibular salivary gland formation type II pneumocyte differentiation negative regulation of extrinsic apoptotic signaling pathway in absence of ligand digestive tract development regulation of epithelial cell proliferation epithelial tube branching involved in lung morphogenesis positive regulation of lymphocyte proliferation positive regulation of transcription by RNA polymerase II phosphatidylinositol phosphate biosynthetic process phosphatidylinositol-3-phosphate biosynthetic process peptidyl-tyrosine phosphorylation regulation of signaling receptor activity positive regulation of protein kinase B signaling positive regulation of G1/S transition of mitotic cell cycle Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2255 14165 Ensembl ENSG00000070193 ENSMUSG00000021732 UniProt O15520 O35565 RefSeq (mRNA) NM_004465 NM_008002 RefSeq (protein) NP_004456 NP_032028 Location (UCSC) Chr 5: 44.3 – 44.39 Mb Chr 13: 118.81 – 118.93 Mb PubMed search
Wikidata
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Fibroblast growth factor 10 is a protein that in humans is encoded by the FGF10 gene.

Function

The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. Fibroblast growth factor 10 is a paracrine signaling molecule seen first in the limb bud and organogenesis development. FGF10 starts the developing of limbs and its involved in the branching of morphogenesis in multiple organs such as the lungs, skin, ear and salivary glands. During the limb development Tbx4/Tbx5 stimulate the production of FGF10 in the lateral plate mesoderm where it will create an epithelial-mesenchymal FGF signal with FGF8. This positive feedback loop will increase the amount of mesenchyme resulting in a bulge. Afterwards, FGF10 will induce the formation of apical ectodermal ridge (AER) where the foot and hands will be formed. Lung development uses the same epithelial-mesenchymal signaling from FGF10 in the foregut mesenchyme with FGFR2 in the foregut epithelium. FGF10 signaling is required for epithelial branching. Therefore, all branching morphogen organs such as the lungs, skin, ear and salivary glands required the constant expression of FGF10. This protein exhibits mitogenic activity for keratinizing epidermal cells, but essentially no activity for fibroblasts, which is similar to the biological activity of FGF7.

Clinical significance

Nonsense mutations may also occur with the absence of FGF10 such as LADD and ALSG syndrome. Nevertheless, complications may arise from FGF10 signaling such as pancreatic and breast cancer. Moreover, studies have identified variants near the FGF10 locus as a genetic risk factor for breast cancer susceptibility. Although this gene is also implicated to be a primary factor in the process of wound healing. Heterozygous FGF10 variants and childhood intestinal lung disease (child) linked to potential early lethal outcomes. Also, FGF10 variants have been associated with abnormal epithelial repair. FGF10 haploinsufficiency have been shown to increased risk of chronic‐obstructive pulmonary disease (COPD). Individuals with haploinsufficiency for FGF10 have significantly reduced Tiffeneau index, resembling chronic restrictive and obstructive pulmonary disease.

Animal studies

FGF10 knockout mice die right after birth. The mice showed no developing organs such as lungs, salivary glands, kidney or definitive limbs once autopsied. Studies of the mouse homolog suggested that this gene is required for embryonic epidermal morphogenesis including brain development, lung morphogenesis, and initiation of limb bud formation. FGF Knockout mice also have impaired epicardial cell expansion following neonatal heart injury, as well as reduced expression of epicardial markers Wt1 and Tbx18, and mesenchymal markers such as Snai1, Twist1, and Postn. Mice deficient for FGF10 fail to develop normal mammary glands. Guinea Pig model has shown that FGF10 monoclonal antibody can decrease the number of inflammatory cells in the dermis and its inhibitory effect on inflammatory cells is like that of hydrocortisone butyrate.

Interactions

FGF10 has been shown to interact with Heparan sulfate and Toll-like receptors.

See also

• Turtle shell

Further reading

• Igarashi M, Finch PW, Aaronson SA (May 1998). "Characterization of recombinant human fibroblast growth factor (FGF)-10 reveals functional similarities with keratinocyte growth factor (FGF-7)". The Journal of Biological Chemistry. 273 (21): 13230–13235. doi:10.1074/jbc.273.21.13230. PMID 9582367.
• Sekine K, Ohuchi H, Fujiwara M, Yamasaki M, Yoshizawa T, Sato T, et al. (January 1999). "Fgf10 is essential for limb and lung formation". Nature Genetics. 21 (1): 138–141. doi:10.1038/5096. PMID 9916808. S2CID 7296564.
• Jimenez PA, Rampy MA (February 1999). "Keratinocyte growth factor-2 accelerates wound healing in incisional wounds". The Journal of Surgical Research. 81 (2): 238–242. doi:10.1006/jsre.1998.5501. PMID 9927546.
• Ropiquet F, Giri D, Kwabi-Addo B, Schmidt K, Ittmann M (September 2000). "FGF-10 is expressed at low levels in the human prostate". The Prostate. 44 (4): 334–338. doi:10.1002/1097-0045(20000901)44:4<334::AID-PROS11>3.0.CO;2-G. PMID 10951499. S2CID 35828553.
• Marchese C, Felici A, Visco V, Lucania G, Igarashi M, Picardo M, et al. (April 2001). "Fibroblast growth factor 10 induces proliferation and differentiation of human primary cultured keratinocytes". The Journal of Investigative Dermatology. 116 (4): 623–628. doi:10.1046/j.0022-202x.2001.01280.x. PMID 11286634.
• Bagai S, Rubio E, Cheng JF, Sweet R, Thomas R, Fuchs E, et al. (June 2002). "Fibroblast growth factor-10 is a mitogen for urothelial cells". The Journal of Biological Chemistry. 277 (26): 23828–23837. doi:10.1074/jbc.M201658200. PMID 11923311.
• Yeh BK, Igarashi M, Eliseenkova AV, Plotnikov AN, Sher I, Ron D, et al. (March 2003). "Structural basis by which alternative splicing confers specificity in fibroblast growth factor receptors". Proceedings of the National Academy of Sciences of the United States of America. 100 (5): 2266–2271. Bibcode:2003PNAS..100.2266Y. doi:10.1073/pnas.0436500100. PMC 151329. PMID 12591959.
• Upadhyay D, Lecuona E, Comellas A, Kamp DW, Sznajder JI (June 2003). "Fibroblast growth factor-10 upregulates Na,K-ATPase via the MAPK pathway". FEBS Letters. 545 (2–3): 173–176. Bibcode:2003FEBSL.545..173U. doi:10.1016/S0014-5793(03)00527-1. PMID 12804770. S2CID 40221645.
• Izvolsky KI, Zhong L, Wei L, Yu Q, Nugent MA, Cardoso WV (October 2003). "Heparan sulfates expressed in the distal lung are required for Fgf10 binding to the epithelium and for airway branching". American Journal of Physiology. Lung Cellular and Molecular Physiology. 285 (4): L838 – L846. doi:10.1152/ajplung.00081.2003. PMID 12818887. S2CID 23937684.
• Tomlinson DC, Grindley JC, Thomson AA (April 2004). "Regulation of Fgf10 gene expression in the prostate: identification of transforming growth factor-beta1 and promoter elements". Endocrinology. 145 (4): 1988–1995. doi:10.1210/en.2003-0842. PMID 14726452.
• Upadhyay D, Bundesmann M, Panduri V, Correa-Meyer E, Kamp DW (July 2004). "Fibroblast growth factor-10 attenuates H2O2-induced alveolar epithelial cell DNA damage: role of MAPK activation and DNA repair". American Journal of Respiratory Cell and Molecular Biology. 31 (1): 107–113. doi:10.1165/rcmb.2003-0064OC. PMID 14975937.
• Theodorou V, Boer M, Weigelt B, Jonkers J, van der Valk M, Hilkens J (August 2004). "Fgf10 is an oncogene activated by MMTV insertional mutagenesis in mouse mammary tumors and overexpressed in a subset of human breast carcinomas". Oncogene. 23 (36): 6047–6055. doi:10.1038/sj.onc.1207816. PMID 15208658. S2CID 19488696.
• Ibrahimi OA, Yeh BK, Eliseenkova AV, Zhang F, Olsen SK, Igarashi M, et al. (January 2005). "Analysis of mutations in fibroblast growth factor (FGF) and a pathogenic mutation in FGF receptor (FGFR) provides direct evidence for the symmetric two-end model for FGFR dimerization". Molecular and Cellular Biology. 25 (2): 671–684. doi:10.1128/MCB.25.2.671-684.2005. PMC 543411. PMID 15632068.
• Entesarian M, Matsson H, Klar J, Bergendal B, Olson L, Arakaki R, et al. (February 2005). "Mutations in the gene encoding fibroblast growth factor 10 are associated with aplasia of lacrimal and salivary glands". Nature Genetics. 37 (2): 125–127. doi:10.1038/ng1507. PMID 15654336. S2CID 36863833.
• Kovacs D, Falchi M, Cardinali G, Raffa S, Carducci M, Cota C, et al. (February 2005). "Immunohistochemical analysis of keratinocyte growth factor and fibroblast growth factor 10 expression in psoriasis". Experimental Dermatology. 14 (2): 130–137. doi:10.1111/j.0906-6705.2005.00261.x. PMID 15679583. S2CID 36797243.
• Ye F, Duvillié B, Scharfmann R (February 2005). "Fibroblast growth factors 7 and 10 are expressed in the human embryonic pancreatic mesenchyme and promote the proliferation of embryonic pancreatic epithelial cells". Diabetologia. 48 (2): 277–281. doi:10.1007/s00125-004-1638-6. PMID 15690149.
• Beer HD, Bittner M, Niklaus G, Munding C, Max N, Goppelt A, et al. (August 2005). "The fibroblast growth factor binding protein is a novel interaction partner of FGF-7, FGF-10 and FGF-22 and regulates FGF activity: implications for epithelial repair". Oncogene. 24 (34): 5269–5277. doi:10.1038/sj.onc.1208560. PMID 15806171. S2CID 75364.

External links

• OMIM entry on aplasia of lacrimal and salivary glands