Find FGF18 Products
Gene FGF18: FGF18_HUMAN
Fibroblast Growth Factor 18
NCBI/Entrez	8817
HGNC	3674
UniProt/Swiss-Prot/ UniProt/TrEMBL	O76093 Q6UWF1
Ensembl	ENSG00000156427
OMIM	603726
GeneCards	GC05P170779
Synonyms: FGF-18, Fibroblast growth factor 18 precursor, UNQ420/PRO856, zFGF5, ZFGF5

Fibroblast Growth Factor 18 (FGF18)

The human FGF18 (map locus: Entrez/HGNC: 5q34, Whitmore TE, et al. (2000); Ensembl: 5q35.1) gene product, fibroblast growth factor-18/FGF18, is a 207 AA long precursor protein that is cleaved to mature 180 AA FGF18 by removal of a 27 AA signaling sequence. FGF18 has two potential N-linked glycosylation sites, Asn39 and Asn137. Within the FGF family, FGF18 is most similar to FGF8 and FGF17, Maruoka Y, et al. (1998). FGF8, FGF17 and FGF18 compose an FGF subfamily that is involved in embryo development. The role of FGF18 in embryogenesis and post-natal development has been reviewed recently, Haque T, et al. (2007).

FGF18 is a pleiotrophic growth factor involved in the development of early embryonic as well as adult tissues. FGF18 is present at high levels in trophoblast stem (TS) cells and preimplantation embryos, Zhong W, et al. (2006). It is also found in the isthmus organizer within the midbrain hindbrain boundary (MHB), Ohuchi H, et al. (2000); early cortical neurons, Hasegawa H, et al. (2004), embryonic lung tissue, Usui H, et al. (2004) and limb bud mesenchyme, Davidson D, et al. (2005). FGF18 is expressed in hair follicles, Kawano M, et al. (2005). Fgf18 is expressed in osteogenic mesenchymal cells and differentiating osteoblasts during calvarial bone development and in perichondrium of developing long bones, Ohbayashi N, et al. (2002), Liu Z et al. (2002).

FGF18 may be an early marker for colorectal carcinoma, Shimokawa T, et al. (2003). Its expression is up-regulated in colorectal tumors and exerts pro-tumorigenic effects in both epithelial and stromal compartments as a survival factor, Sonvilla G, et al. (2008).

FGF18 has been studied most extensively as a factor involved in endochondral bone development (endochondral ossification) through regulation of both chondrogenesis and osteogenesis, Ohbayashi N, et al. (2002). It is a trophic factor for mature chondrocytes and their progenitors, Ellsworth JL, et al. (2002) and a positive regulator of osteogenesis, Beak JY, et al. (2007). FGF18 negatively regulates chondrogenesis through fibroblast growth factor receptor 3 (FGFR3) and positively regulates osteogenesis through other FGF receptors. Binding of FGF18 to FGFR3 regulates proliferation, differentiation and matrix formation by articular and growth plate chondrocytes. FGFR3 inhibits chondrocyte proliferation, Wang Q, et al. (2001). FGF18 suppresses mesenchyme cell (chondrocyte progenitor) proliferation and promotes differentiation to chondrocytes and production of cartilage matrix. Davidson D, et al. (2005).

FGF18 signaling through FGF receptor 3 may be an important target for therapeutic intervention to address degenerative disorders of cartilage metabolism such as osteoarthritis (OA) and achondroplasia, Moore EE, et al. (2005) and Valverde-Franco G, et al. (2006).

Sigma offers antibodies and shRNAs useful for the study of FGF18 gene products..

References:

1. Beak JY, et al. (2007) Krüppel-like zinc finger protein Glis3 promotes osteoblast differentiation by regulating FGF18 expression. J Bone Miner Res. 22: 1234-1244.
2. Davidson D, et al. (2005) Fibroblast growth factor (FGF) 18 signals through FGF receptor 3 to promote chondrogenesis. J Biol Chem. 280: 20509-20515.
3. Ellsworth JL, et al. (2002) Fibroblast growth factor-18 is a trophic factor for mature chondrocytes and their progenitors. Osteoarthritis Cartilage. 10: 308-320.
4. Haque T, et al. (2007) A review of FGF18: Its expression, signaling pathways and possible functions during embryogenesis and post-natal development. Histol Histopathol. 2: 97-105.
5. Hasegawa H, et al. (2004) Laminar patterning in the developing neocortex by temporally coordinated fibroblast growth factor signaling. J Neurosci. 24: 8711-8719.
6. Kawano M, et al. (2005) Comprehensive analysis of FGF and FGFR expression in skin: FGF18 is highly expressed in hair follicles and capable of inducing anagen from telogen stage hair follicles. J Invest Dermatol. 124: 877-885.
7. Liu Z, et al. (2002) Coordination of chondrogenesis and osteogenesis by fibroblast growth factor 18. Genes Dev. 16: 859-869.
8. Maruoka Y, et al. (1998) Comparison of the expression of three highly related genes, Fgf8, Fgf17 and Fgf18, in the mouse embryo. Mech Dev. 74: 175-187.
9. Moore EE, et al. (2005) Fibroblast growth factor-18 stimulates chondrogenesis and cartilage repair in a rat model of injury-induced osteoarthritis. Osteoarthritis Cartilage. 13: 623-631.
10. Ohbayashi N, et al. (2002) FGF18 is required for normal cell proliferation and differentiation during osteogenesis and chondrogenesis. Genes Dev. 16: 870-879.
11. Ohuchi H, et al. (2000) Involvement of fibroblast growth factor (FGF)18-FGF8 signaling in specification of left-right asymmetry and brain and limb development of the chick embryo. Mech Dev. 95: 55-66.
12. Shimokawa T, et al. (2003) Involvement of the FGF18 gene in colorectal carcinogenesis, as a novel downstream target of the beta-catenin/T-cell factor complex. Cancer Res. 63: 6116-6120.
13. Sonvilla G, et al. (2008) FGF18 in colorectal tumour cells: autocrine and paracrine effects. Carcinogenesis. 29: 15-24.
14. Usui H, et al. (2004) Fgf18 is required for embryonic lung alveolar development. Biochem Biophys Res Commun. 322: 887-892.
15. Valverde-Franco G, et al. (2006) Defects in articular cartilage metabolism and early arthritis in fibroblast growth factor receptor 3 deficient mice. Hum Mol Genet. 15: 1783-1792.
16. Wang Q, et al. (2001) Differential regulation of endochondral bone growth and joint development by FGFR1 and FGFR3 tyrosine kinase domains. Development. 128: 3867-3876.
17. Whitmore TE, et al. (2000) Assignment of fibroblast growth factor 18 (FGF18) to human chromosome 5q34 by use of radiation hybrid mapping and fluorescence in situ hybridization. Cytogenet Cell Genet. 90: 231-233.
18. Zhong W, et al. (2006) FGF ligand family mRNA expression profile for mouse preimplantation embryos, early gestation human placenta, and mouse trophoblast stem cells. Mol Reprod Dev. 73: 540-550.M