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Gene Review

Fgf10  -  fibroblast growth factor 10

Mus musculus

Synonyms: AEY17, BB213776, FGF-10, Fgf-10, Fibroblast growth factor 10, ...
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Disease relevance of Fgf10

  • Defective growth in the anterior palate of Msx1-/- and Fgf10-/- mice leads to a complete cleft palate and supports the anterior-to-posterior direction of palatal closure [1].
  • Congenital heart defects in Fgfr2-IIIb and Fgf10 mutant mice [2].
  • Fgfr2-IIIb and Fgf10 mutant mice provide new models for common components of congenital heart disease [2].
  • FGF-10 deficient mutant male mouse revealed normal corporal bodies with failure of the urethral plate to fuse ventrally consistent with hypospadias [3].
  • A survey of primary human breast carcinomas revealed strongly elevated Fgf10 mRNA levels in approximately 10% of the tumors tested, suggesting that Fgf10 may also be involved in oncogenicity of a subset of human breast cancers [4].
  • Our observations indicate that stromal FGF10 expression may facilitate the multifocal histology observed in prostate adenocarcinoma and suggest the FGF10/FGFR1 axis as a potential therapeutic target in treating hormone-sensitive or refractory prostate cancer [5].

High impact information on Fgf10

  • Fgf10(+/-) mice have a phenotype similar to ALSG, providing a model for this disorder [6].
  • Mutations in the gene encoding fibroblast growth factor 10 are associated with aplasia of lacrimal and salivary glands [6].
  • FGF7 and FGF10, the closest relatives of FGF22, share this activity; other FGFs have distinct effects [7].
  • In Fgf10-/- embryos, limb bud formation was initiated but outgrowth of the limb buds did not occur; however, formation of the clavicles was not affected [8].
  • In mouse, mesodermal Fgf10 acting redundantly with neural Fgf3 is required for induction of the placode [9].

Chemical compound and disease context of Fgf10


Biological context of Fgf10


Anatomical context of Fgf10

  • The signaling pathways between endoderm-derived gastric epithelium and the surrounding mesenchyme are largely unknown; however, the developmental expression profile of the IIIb isoform of Fgfr2 (Fgfr2b) and its main ligand, Fgf10, suggest that they may be strong candidates [11].
  • However, Fgf10-null epithelial cells running though the eyelid groove do not exhibit typical cuboid shape or sufficient proliferation [13].
  • Fibroblast growth factors (FGFs) often mediate epithelial-mesenchymal interactions and mesenchymal Fgf10 is essential for epithelial branching in the developing lung [15].
  • In contrast, despite its vital role during limb-bud formation, Fgf10 appears not to be primarily essential for initial outgrowth of GT, as extrapolated from Fgf10(-/-) GTs [16].
  • The temporal and spatial pattern of gene expression suggests that Fgf10 plays a role in directional outgrowth and possibly induction of epithelial buds, and that positive and negative regulators of Fgf10 are produced by the endoderm [17].

Associations of Fgf10 with chemical compounds

  • We show that altering endogenous gradients of HS sulfation with sodium chlorate or over-O-sulfated synthetic heparin in lung organ cultures dramatically decreases Fgf10 binding [18].
  • The mitogenic activity of FGF-10 could be distinguished from that of KGF by its different sensitivity to heparin and lack of neutralization by a KGF monoclonal antibody [19].
  • Retinoic acid selectively regulates Fgf10 expression and maintains cell identity in the prospective lung field of the developing foregut [20].
  • In cultures of UGS, the FGF-10 null phenotype was partially reversed by the addition of FGF-10 and testosterone, resulting in the formation of prostatic buds [21].
  • Herein, we demonstrate that FGF10 stimulation of mouse lung epithelial cells (MLE15) overexpressing mSpry2 results in both mSpry2 tyrosine phosphorylation and differential binding of mSpry2 to several key upstream target proteins in the MAP kinase-activating pathway [22].

Enzymatic interactions of Fgf10

  • The failure of exogenous FGF10 to phosphorylate its known downstream targets ERK and AKT in lung mesenchymal cultures strongly suggests that FGF10 acts indirectly on the progenitor population via an epithelial intermediate [23].

Regulatory relationships of Fgf10


Other interactions of Fgf10


Analytical, diagnostic and therapeutic context of Fgf10


  1. Regional regulation of palatal growth and patterning along the anterior-posterior axis in mice. Hilliard, S.A., Yu, L., Gu, S., Zhang, Z., Chen, Y.P. J. Anat. (2005) [Pubmed]
  2. Congenital heart defects in Fgfr2-IIIb and Fgf10 mutant mice. Marguerie, A., Bajolle, F., Zaffran, S., Brown, N.A., Dickson, C., Buckingham, M.E., Kelly, R.G. Cardiovasc. Res. (2006) [Pubmed]
  3. Anatomical studies of the fibroblast growth factor-10 mutant, Sonic Hedge Hog mutant and androgen receptor mutant mouse genital tubercle. Yucel, S., Liu, W., Cordero, D., Donjacour, A., Cunha, G., Baskin, L.S. Adv. Exp. Med. Biol. (2004) [Pubmed]
  4. Fgf10 is an oncogene activated by MMTV insertional mutagenesis in mouse mammary tumors and overexpressed in a subset of human breast carcinomas. Theodorou, V., Boer, M., Weigelt, B., Jonkers, J., van der Valk, M., Hilkens, J. Oncogene (2004) [Pubmed]
  5. Enhanced paracrine FGF10 expression promotes formation of multifocal prostate adenocarcinoma and an increase in epithelial androgen receptor. Memarzadeh, S., Xin, L., Mulholland, D.J., Mansukhani, A., Wu, H., Teitell, M.A., Witte, O.N. Cancer. Cell (2007) [Pubmed]
  6. Mutations in the gene encoding fibroblast growth factor 10 are associated with aplasia of lacrimal and salivary glands. Entesarian, M., Matsson, H., Klar, J., Bergendal, B., Olson, L., Arakaki, R., Hayashi, Y., Ohuchi, H., Falahat, B., Bolstad, A.I., Jonsson, R., Wahren-Herlenius, M., Dahl, N. Nat. Genet. (2005) [Pubmed]
  7. FGF22 and its close relatives are presynaptic organizing molecules in the mammalian brain. Umemori, H., Linhoff, M.W., Ornitz, D.M., Sanes, J.R. Cell (2004) [Pubmed]
  8. Fgf10 is essential for limb and lung formation. Sekine, K., Ohuchi, H., Fujiwara, M., Yamasaki, M., Yoshizawa, T., Sato, T., Yagishita, N., Matsui, D., Koga, Y., Itoh, N., Kato, S. Nat. Genet. (1999) [Pubmed]
  9. FGF8 initiates inner ear induction in chick and mouse. Ladher, R.K., Wright, T.J., Moon, A.M., Mansour, S.L., Schoenwolf, G.C. Genes Dev. (2005) [Pubmed]
  10. Efficacy of keratinocyte growth factor-2 in dextran sulfate sodium-induced murine colitis. Miceli, R., Hubert, M., Santiago, G., Yao, D.L., Coleman, T.A., Huddleston, K.A., Connolly, K. J. Pharmacol. Exp. Ther. (1999) [Pubmed]
  11. Stomach development is dependent on fibroblast growth factor 10/fibroblast growth factor receptor 2b-mediated signaling. Spencer-Dene, B., Sala, F.G., Bellusci, S., Gschmeissner, S., Stamp, G., Dickson, C. Gastroenterology (2006) [Pubmed]
  12. Fgf3 signaling from the ventral diencephalon is required for early specification and subsequent survival of the zebrafish adenohypophysis. Herzog, W., Sonntag, C., von der Hardt, S., Roehl, H.H., Varga, Z.M., Hammerschmidt, M. Development (2004) [Pubmed]
  13. A dual role of FGF10 in proliferation and coordinated migration of epithelial leading edge cells during mouse eyelid development. Tao, H., Shimizu, M., Kusumoto, R., Ono, K., Noji, S., Ohuchi, H. Development (2005) [Pubmed]
  14. Unique functions of Sonic hedgehog signaling during external genitalia development. Haraguchi, R., Mo, R., Hui, C., Motoyama, J., Makino, S., Shiroishi, T., Gaffield, W., Yamada, G. Development (2001) [Pubmed]
  15. Lung hypoplasia and neonatal death in Fgf9-null mice identify this gene as an essential regulator of lung mesenchyme. Colvin, J.S., White, A.C., Pratt, S.J., Ornitz, D.M. Development (2001) [Pubmed]
  16. Molecular analysis of external genitalia formation: the role of fibroblast growth factor (Fgf) genes during genital tubercle formation. Haraguchi, R., Suzuki, K., Murakami, R., Sakai, M., Kamikawa, M., Kengaku, M., Sekine, K., Kawano, H., Kato, S., Ueno, N., Yamada, G. Development (2000) [Pubmed]
  17. Fibroblast growth factor 10 (FGF10) and branching morphogenesis in the embryonic mouse lung. Bellusci, S., Grindley, J., Emoto, H., Itoh, N., Hogan, B.L. Development (1997) [Pubmed]
  18. Heparan sulfates expressed in the distal lung are required for Fgf10 binding to the epithelium and for airway branching. Izvolsky, K.I., Zhong, L., Wei, L., Yu, Q., Nugent, M.A., Cardoso, W.V. Am. J. Physiol. Lung Cell Mol. Physiol. (2003) [Pubmed]
  19. Characterization of recombinant human fibroblast growth factor (FGF)-10 reveals functional similarities with keratinocyte growth factor (FGF-7). Igarashi, M., Finch, P.W., Aaronson, S.A. J. Biol. Chem. (1998) [Pubmed]
  20. Retinoic acid selectively regulates Fgf10 expression and maintains cell identity in the prospective lung field of the developing foregut. Desai, T.J., Malpel, S., Flentke, G.R., Smith, S.M., Cardoso, W.V. Dev. Biol. (2004) [Pubmed]
  21. FGF-10 plays an essential role in the growth of the fetal prostate. Donjacour, A.A., Thomson, A.A., Cunha, G.R. Dev. Biol. (2003) [Pubmed]
  22. mSprouty2 inhibits FGF10-activated MAP kinase by differentially binding to upstream target proteins. Tefft, D., Lee, M., Smith, S., Crowe, D.L., Bellusci, S., Warburton, D. Am. J. Physiol. Lung Cell Mol. Physiol. (2002) [Pubmed]
  23. Fgf10 expression identifies parabronchial smooth muscle cell progenitors and is required for their entry into the smooth muscle cell lineage. Mailleux, A.A., Kelly, R., Veltmaat, J.M., De Langhe, S.P., Zaffran, S., Thiery, J.P., Bellusci, S. Development (2005) [Pubmed]
  24. Growth arrest specific gene 1 acts as a region-specific mediator of the Fgf10/Fgf8 regulatory loop in the limb. Liu, Y., Liu, C., Yamada, Y., Fan, C.M. Development (2002) [Pubmed]
  25. Tbx5 is essential for forelimb bud initiation following patterning of the limb field in the mouse embryo. Agarwal, P., Wylie, J.N., Galceran, J., Arkhitko, O., Li, C., Deng, C., Grosschedl, R., Bruneau, B.G. Development (2003) [Pubmed]
  26. BMP4 modulates fibroblast growth factor-mediated induction of proximal and distal lung differentiation in mouse embryonic tracheal epithelium in mesenchyme-free culture. Hyatt, B.A., Shangguan, X., Shannon, J.M. Dev. Dyn. (2002) [Pubmed]
  27. Bmp7 regulates branching morphogenesis of the lacrimal gland by promoting mesenchymal proliferation and condensation. Dean, C., Ito, M., Makarenkova, H.P., Faber, S.C., Lang, R.A. Development (2004) [Pubmed]
  28. Disruption of Fgf10/Fgfr2b-coordinated epithelial-mesenchymal interactions causes cleft palate. Rice, R., Spencer-Dene, B., Connor, E.C., Gritli-Linde, A., McMahon, A.P., Dickson, C., Thesleff, I., Rice, D.P. J. Clin. Invest. (2004) [Pubmed]
  29. Gene expression profiles of mouse submandibular gland development: FGFR1 regulates branching morphogenesis in vitro through BMP- and FGF-dependent mechanisms. Hoffman, M.P., Kidder, B.L., Steinberg, Z.L., Lakhani, S., Ho, S., Kleinman, H.K., Larsen, M. Development (2002) [Pubmed]
  30. The dominant hemimelia mutation uncouples epithelial-mesenchymal interactions and disrupts anterior mesenchyme formation in mouse hindlimbs. Lettice, L., Hecksher-Sørensen, J., Hill, R.E. Development (1999) [Pubmed]
  31. Fibroblast growth factor receptor 2 (FGFR2)-mediated reciprocal regulation loop between FGF8 and FGF10 is essential for limb induction. Xu, X., Weinstein, M., Li, C., Naski, M., Cohen, R.I., Ornitz, D.M., Leder, P., Deng, C. Development (1998) [Pubmed]
  32. Fibroblast growth factor 10 is required for proper development of the mouse whiskers. Ohuchi, H., Tao, H., Ohata, K., Itoh, N., Kato, S., Noji, S., Ono, K. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  33. Associations of FGF-3 and FGF-10 with signaling networks regulating tooth morphogenesis. Kettunen, P., Laurikkala, J., Itäranta, P., Vainio, S., Itoh, N., Thesleff, I. Dev. Dyn. (2000) [Pubmed]
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