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.[2]
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. Although this gene is also implicated to be a primary factor in the process of wound healing.[2]
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.[3]
References
↑Emoto H, Tagashira S, Mattei MG, Yamasaki M, Hashimoto G, Katsumata T, Negoro T, Nakatsuka M, Birnbaum D, Coulier F, Itoh N (September 1997). "Structure and expression of human fibroblast growth factor-10". The Journal of Biological Chemistry. 272 (37): 23191–4. doi:10.1074/jbc.272.37.23191. PMID9287324.
↑Itoh N, Ohta H (2014). "Fgf10: a paracrine-signaling molecule in development, disease, and regenerative medicine". Current Molecular Medicine. 14 (4): 504–9. doi:10.2174/1566524014666140414204829. PMID24730525.
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): 13230–5. doi:10.1074/jbc.273.21.13230. PMID9582367.
Sekine K, Ohuchi H, Fujiwara M, Yamasaki M, Yoshizawa T, Sato T, Yagishita N, Matsui D, Koga Y, Itoh N, Kato S (January 1999). "Fgf10 is essential for limb and lung formation". Nature Genetics. 21 (1): 138–41. doi:10.1038/5096. PMID9916808.
Jimenez PA, Rampy MA (February 1999). "Keratinocyte growth factor-2 accelerates wound healing in incisional wounds". The Journal of Surgical Research. 81 (2): 238–42. doi:10.1006/jsre.1998.5501. PMID9927546.
Marchese C, Felici A, Visco V, Lucania G, Igarashi M, Picardo M, Frati L, Torrisi MR (April 2001). "Fibroblast growth factor 10 induces proliferation and differentiation of human primary cultured keratinocytes". The Journal of Investigative Dermatology. 116 (4): 623–8. doi:10.1046/j.0022-202x.2001.01280.x. PMID11286634.
Bagai S, Rubio E, Cheng JF, Sweet R, Thomas R, Fuchs E, Grady R, Mitchell M, Bassuk JA (June 2002). "Fibroblast growth factor-10 is a mitogen for urothelial cells". The Journal of Biological Chemistry. 277 (26): 23828–37. doi:10.1074/jbc.M201658200. PMID11923311.
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): 173–6. doi:10.1016/S0014-5793(03)00527-1. PMID12804770.
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): L838–46. doi:10.1152/ajplung.00081.2003. PMID12818887.
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): 1988–95. doi:10.1210/en.2003-0842. PMID14726452.
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): 107–13. doi:10.1165/rcmb.2003-0064OC. PMID14975937.
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): 6047–55. doi:10.1038/sj.onc.1207816. PMID15208658.
Entesarian M, Matsson H, Klar J, Bergendal B, Olson L, Arakaki R, Hayashi Y, Ohuchi H, Falahat B, Bolstad AI, Jonsson R, Wahren-Herlenius M, Dahl N (February 2005). "Mutations in the gene encoding fibroblast growth factor 10 are associated with aplasia of lacrimal and salivary glands". Nature Genetics. 37 (2): 125–7. doi:10.1038/ng1507. PMID15654336.
Kovacs D, Falchi M, Cardinali G, Raffa S, Carducci M, Cota C, Amantea A, Torrisi MR, Picardo M (February 2005). "Immunohistochemical analysis of keratinocyte growth factor and fibroblast growth factor 10 expression in psoriasis". Experimental Dermatology. 14 (2): 130–7. doi:10.1111/j.0906-6705.2005.00261.x. PMID15679583.
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): 277–81. doi:10.1007/s00125-004-1638-6. PMID15690149.
Beer HD, Bittner M, Niklaus G, Munding C, Max N, Goppelt A, Werner S (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): 5269–77. doi:10.1038/sj.onc.1208560. PMID15806171.