1. Function

2. Clinical significance

3. Animal studies

4. References

5. Further reading

6. External links

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.^[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

Further reading

• {{cite journal | vauthors = Igarashi M, Finch PW, Aaronson SA | title = Characterization of recombinant human fibroblast growth factor (FGF)-10 reveals functional similarities with keratinocyte growth factor (FGF-7) | journal = The Journal of Biological Chemistry | volume = 273 | issue = 21 | pages = 13230–5 | date = May 1998 | pmid = 9582367 | doi = 10.1074/jbc.273.21.13230 | author3-link = Stuart A. Aaronson }}
• {{cite journal | vauthors = Sekine K, Ohuchi H, Fujiwara M, Yamasaki M, Yoshizawa T, Sato T, Yagishita N, Matsui D, Koga Y, Itoh N, Kato S | title = Fgf10 is essential for limb and lung formation | journal = Nature Genetics | volume = 21 | issue = 1 | pages = 138–41 | date = January 1999 | pmid = 9916808 | doi = 10.1038/5096 }}
• {{cite journal | vauthors = Jimenez PA, Rampy MA | title = Keratinocyte growth factor-2 accelerates wound healing in incisional wounds | journal = The Journal of Surgical Research | volume = 81 | issue = 2 | pages = 238–42 | date = February 1999 | pmid = 9927546 | doi = 10.1006/jsre.1998.5501 }}
• {{cite journal | vauthors = Ropiquet F, Giri D, Kwabi-Addo B, Schmidt K, Ittmann M | title = FGF-10 is expressed at low levels in the human prostate | journal = The Prostate | volume = 44 | issue = 4 | pages = 334–8 | date = September 2000 | pmid = 10951499 | doi = 10.1002/1097-0045(20000901)44:4<334::AID-PROS11>3.0.CO;2-G }}
• {{cite journal | vauthors = Marchese C, Felici A, Visco V, Lucania G, Igarashi M, Picardo M, Frati L, Torrisi MR | title = Fibroblast growth factor 10 induces proliferation and differentiation of human primary cultured keratinocytes | journal = The Journal of Investigative Dermatology | volume = 116 | issue = 4 | pages = 623–8 | date = April 2001 | pmid = 11286634 | doi = 10.1046/j.0022-202x.2001.01280.x }}
• {{cite journal | vauthors = Bagai S, Rubio E, Cheng JF, Sweet R, Thomas R, Fuchs E, Grady R, Mitchell M, Bassuk JA | title = Fibroblast growth factor-10 is a mitogen for urothelial cells | journal = The Journal of Biological Chemistry | volume = 277 | issue = 26 | pages = 23828–37 | date = June 2002 | pmid = 11923311 | doi = 10.1074/jbc.M201658200 }}
• {{cite journal | vauthors = Yeh BK, Igarashi M, Eliseenkova AV, Plotnikov AN, Sher I, Ron D, Aaronson SA, Mohammadi M | title = Structural basis by which alternative splicing confers specificity in fibroblast growth factor receptors | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 100 | issue = 5 | pages = 2266–71 | date = March 2003 | pmid = 12591959 | pmc = 151329 | doi = 10.1073/pnas.0436500100 }}
• {{cite journal | vauthors = Upadhyay D, Lecuona E, Comellas A, Kamp DW, Sznajder JI | title = Fibroblast growth factor-10 upregulates Na,K-ATPase via the MAPK pathway | journal = FEBS Letters | volume = 545 | issue = 2-3 | pages = 173–6 | date = June 2003 | pmid = 12804770 | doi = 10.1016/S0014-5793(03)00527-1 }}
• {{cite journal | vauthors = Izvolsky KI, Zhong L, Wei L, Yu Q, Nugent MA, Cardoso WV | title = Heparan sulfates expressed in the distal lung are required for Fgf10 binding to the epithelium and for airway branching | journal = American Journal of Physiology. Lung Cellular and Molecular Physiology | volume = 285 | issue = 4 | pages = L838-46 | date = October 2003 | pmid = 12818887 | doi = 10.1152/ajplung.00081.2003 }}
• {{cite journal | vauthors = Tomlinson DC, Grindley JC, Thomson AA | title = Regulation of Fgf10 gene expression in the prostate: identification of transforming growth factor-beta1 and promoter elements | journal = Endocrinology | volume = 145 | issue = 4 | pages = 1988–95 | date = April 2004 | pmid = 14726452 | doi = 10.1210/en.2003-0842 }}
• {{cite journal | vauthors = Upadhyay D, Bundesmann M, Panduri V, Correa-Meyer E, Kamp DW | title = Fibroblast growth factor-10 attenuates H2O2-induced alveolar epithelial cell DNA damage: role of MAPK activation and DNA repair | journal = American Journal of Respiratory Cell and Molecular Biology | volume = 31 | issue = 1 | pages = 107–13 | date = July 2004 | pmid = 14975937 | doi = 10.1165/rcmb.2003-0064OC }}
• {{cite journal | vauthors = Theodorou V, Boer M, Weigelt B, Jonkers J, van der Valk M, Hilkens J | title = Fgf10 is an oncogene activated by MMTV insertional mutagenesis in mouse mammary tumors and overexpressed in a subset of human breast carcinomas | journal = Oncogene | volume = 23 | issue = 36 | pages = 6047–55 | date = August 2004 | pmid = 15208658 | doi = 10.1038/sj.onc.1207816 }}
• {{cite journal | vauthors = Ibrahimi OA, Yeh BK, Eliseenkova AV, Zhang F, Olsen SK, Igarashi M, Aaronson SA, Linhardt RJ, Mohammadi M | title = 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 | journal = Molecular and Cellular Biology | volume = 25 | issue = 2 | pages = 671–84 | date = January 2005 | pmid = 15632068 | pmc = 543411 | doi = 10.1128/MCB.25.2.671-684.2005 }}
• {{cite journal | vauthors = 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 | title = Mutations in the gene encoding fibroblast growth factor 10 are associated with aplasia of lacrimal and salivary glands | journal = Nature Genetics | volume = 37 | issue = 2 | pages = 125–7 | date = February 2005 | pmid = 15654336 | doi = 10.1038/ng1507 }}
• {{cite journal | vauthors = Kovacs D, Falchi M, Cardinali G, Raffa S, Carducci M, Cota C, Amantea A, Torrisi MR, Picardo M | title = Immunohistochemical analysis of keratinocyte growth factor and fibroblast growth factor 10 expression in psoriasis | journal = Experimental Dermatology | volume = 14 | issue = 2 | pages = 130–7 | date = February 2005 | pmid = 15679583 | doi = 10.1111/j.0906-6705.2005.00261.x }}
• {{cite journal | vauthors = Ye F, Duvillié B, Scharfmann R | title = Fibroblast growth factors 7 and 10 are expressed in the human embryonic pancreatic mesenchyme and promote the proliferation of embryonic pancreatic epithelial cells | journal = Diabetologia | volume = 48 | issue = 2 | pages = 277–81 | date = February 2005 | pmid = 15690149 | doi = 10.1007/s00125-004-1638-6 }}
• {{cite journal | vauthors = Beer HD, Bittner M, Niklaus G, Munding C, Max N, Goppelt A, Werner S | title = 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 | journal = Oncogene | volume = 24 | issue = 34 | pages = 5269–77 | date = August 2005 | pmid = 15806171 | doi = 10.1038/sj.onc.1208560 }}

External links

• OMIM entry on aplasia of lacrimal and salivary glands

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