fibroblast growth factor 9


Summary: A fibroblast growth factor that was originally identified as a mitogen for GLIAL CELLS. It is expressed primarily in NEURONS.

Top Publications

  1. Barrios F, Filipponi D, Pellegrini M, Paronetto M, Di Siena S, Geremia R, et al. Opposing effects of retinoic acid and FGF9 on Nanos2 expression and meiotic entry of mouse germ cells. J Cell Sci. 2010;123:871-80 pubmed publisher
    ..Finally, we found that recombinant NANOS2 binds to two spermatogonial mRNAs, Gata2 and Taf7l, which are involved in germ-cell differentiation. ..
  2. Yoshioka H, Ishimaru Y, Sugiyama N, Tsunekawa N, Noce T, Kasahara M, et al. Mesonephric FGF signaling is associated with the development of sexually indifferent gonadal primordium in chick embryos. Dev Biol. 2005;280:150-61 pubmed
    ..Our study demonstrated that FGF expressed in the developing mesonephros is involved in the development of the gonad at the sexually indifferent stages through stimulation of gonadal cell proliferation and gonadal marker gene expression. ..
  3. Pirvola U, Zhang X, Mantela J, Ornitz D, Ylikoski J. Fgf9 signaling regulates inner ear morphogenesis through epithelial-mesenchymal interactions. Dev Biol. 2004;273:350-60 pubmed
    ..Together, these data show that Fgf9 signaling is required for inner ear morphogenesis. ..
  4. Gau B, Chen T, Shih Y, Sun H. FUBP3 interacts with FGF9 3' microsatellite and positively regulates FGF9 translation. Nucleic Acids Res. 2011;39:3582-93 pubmed publisher
    ..Altogether, results from this study showed the novel RNA-binding property of FUBP3 and the interaction between FUBP3 and FGF9 3'-UTR UG-repeat promoting FGF9 mRNA translation. ..
  5. del Moral P, De Langhe S, Sala F, Veltmaat J, Tefft D, Wang K, et al. Differential role of FGF9 on epithelium and mesenchyme in mouse embryonic lung. Dev Biol. 2006;293:77-89 pubmed
    Mesothelial Fibroblast Growth Factor 9 (Fgf9) has been demonstrated by inactivation studies in mouse to be critical for the proliferation of the mesenchyme...
  6. Tsai S, Wu M, Chen H, Chuang P, Wing L. Fibroblast growth factor-9 is an endometrial stromal growth factor. Endocrinology. 2002;143:2715-21 pubmed
    ..Herein we demonstrate, for the first time, that FGF-9 is an autocrine estromedin endometrial stromal growth factor that plays roles in cyclic proliferation of uterine endometrial stroma. ..
  7. Abdel Rahman W, Kalinina J, Shoman S, Eissa S, Ollikainen M, Elomaa O, et al. Somatic FGF9 mutations in colorectal and endometrial carcinomas associated with membranous beta-catenin. Hum Mutat. 2008;29:390-7 pubmed publisher
    ..We hypothesized that such tumors might carry mutations in Wnt/beta-catenin target genes. Fibroblast growth factor 9 (FGF9) was an attractive target, as it maps to a common area of loss of heterozygosity (LOH) in ..
  8. Kanda T, Iwasaki T, Nakamura S, Kurokawa T, Ikeda K, Mizusawa H. Self-secretion of fibroblast growth factor-9 supports basal forebrain cholinergic neurons in an autocrine/paracrine manner. Brain Res. 2000;876:22-30 pubmed
    ..Although effective delivery of exogenous FGF-9 into the central nervous system remains a problem to be solved, FGF-9 may be a promising candidate for therapeutic trials in Alzheimer disease. ..
  9. Iwata J, Tung L, Urata M, Hacia J, Pelikan R, Suzuki A, et al. Fibroblast growth factor 9 (FGF9)-pituitary homeobox 2 (PITX2) pathway mediates transforming growth factor ? (TGF?) signaling to regulate cell proliferation in palatal mesenchyme during mouse palatogenesis. J Biol Chem. 2012;287:2353-63 pubmed publisher
    ..We found that fibroblast growth factor 9 (Fgf9) and transcription factor pituitary homeobox 2 (Pitx2) expressions are significantly down-..

More Information


  1. Wu M, Shoji Y, Chuang P, Tsai S. Endometriosis: disease pathophysiology and the role of prostaglandins. Expert Rev Mol Med. 2007;9:1-20 pubmed
    ..In this review, we focus on the expression, regulation and action of prostaglandins in the cellular and molecular mechanisms that contribute to the development and/or maintenance of endometriosis. ..
  2. Wing L, Chuang P, Wu M, Chen H, Tsai S. Expression and mitogenic effect of fibroblast growth factor-9 in human endometriotic implant is regulated by aberrant production of estrogen. J Clin Endocrinol Metab. 2003;88:5547-54 pubmed
  3. Giri D, Ropiquet F, Ittmann M. FGF9 is an autocrine and paracrine prostatic growth factor expressed by prostatic stromal cells. J Cell Physiol. 1999;180:53-60 pubmed
    ..Overexpression of this paracrine and autocrine growth factor may play an important role in the epithelial and stromal proliferation in benign prostatic hyperplasia. ..
  4. Colvin J, Green R, Schmahl J, Capel B, Ornitz D. Male-to-female sex reversal in mice lacking fibroblast growth factor 9. Cell. 2001;104:875-89 pubmed
    ..Here we report male-to-female sex reversal in mice lacking Fibroblast growth factor 9 (Fgf9), demonstrating a novel role for FGF signaling in testicular embryogenesis...
  5. Wu X, Gu M, Huang L, Liu X, Zhang H, Ding X, et al. Multiple synostoses syndrome is due to a missense mutation in exon 2 of FGF9 gene. Am J Hum Genet. 2009;85:53-63 pubmed publisher
    ..Collectively, our data demonstrate a previously uncharacterized mutation in FGF9 as one of the causes of SYNS, implicating an important role of FGF9 in normal joint development. ..
  6. Teishima J, Shoji K, Hayashi T, Miyamoto K, Ohara S, Matsubara A. Relationship between the localization of fibroblast growth factor 9 in prostate cancer cells and postoperative recurrence. Prostate Cancer Prostatic Dis. 2012;15:8-14 pubmed publisher
    b>Fibroblast growth factor 9 (FGF9) enhances cell proliferation and invasiveness in several malignant diseases. The aim of the present study is to investigate the role of FGF9 in postoperative recurrence after radical prostatectomy...
  7. Lovicu F, Overbeek P. Overlapping effects of different members of the FGF family on lens fiber differentiation in transgenic mice. Development. 1998;125:3365-77 pubmed
  8. Kalinina J, Byron S, Makarenkova H, Olsen S, Eliseenkova A, Larochelle W, et al. Homodimerization controls the fibroblast growth factor 9 subfamily's receptor binding and heparan sulfate-dependent diffusion in the extracellular matrix. Mol Cell Biol. 2009;29:4663-78 pubmed publisher
  9. Mattei M, Penault Llorca F, Coulier F, Birnbaum D. The human FGF9 gene maps to chromosomal region 13q11-q12. Genomics. 1995;29:811-2 pubmed
  10. Li Z, Mathew P, Yang J, Starbuck M, Zurita A, Liu J, et al. Androgen receptor-negative human prostate cancer cells induce osteogenesis in mice through FGF9-mediated mechanisms. J Clin Invest. 2008;118:2697-710 pubmed publisher
    ..Androgen receptor-null cells may contribute to the castration-resistant osteoblastic progression of prostate cancer cells in bone and provide a preclinical model for studying therapies that target these cells. ..
  11. Antoine M, Wirz W, Tag C, Gressner A, Marvituna M, Wycislo M, et al. Expression and function of fibroblast growth factor (FGF) 9 in hepatic stellate cells and its role in toxic liver injury. Biochem Biophys Res Commun. 2007;361:335-41 pubmed
    ..Our findings suggest that HSC FGF9 provide a paracrine mitogenic signal to hepatocytes during acute liver injury, while the autocrine FGF9 signaling appears to be not sufficient to induce cell proliferation. ..
  12. Wing L, Chen H, Chuang P, Wu M, Tsai S. The mammalian target of rapamycin-p70 ribosomal S6 kinase but not phosphatidylinositol 3-kinase-Akt signaling is responsible for fibroblast growth factor-9-induced cell proliferation. J Biol Chem. 2005;280:19937-47 pubmed
    ..These studies provide evidence to demonstrate, for the first time, that a novel signaling cascade involving phospholipase Cgamma, calcium, mTOR, and S6K1 is activated by FGF9 in a receptor-specific manner. ..
  13. Chuang P, Sun H, Chen T, Tsai S. Prostaglandin E2 induces fibroblast growth factor 9 via EP3-dependent protein kinase Cdelta and Elk-1 signaling. Mol Cell Biol. 2006;26:8281-92 pubmed
    b>Fibroblast growth factor 9 (FGF-9) is a potent mitogen that controls the proper development of many tissues and organs...
  14. Korf Klingebiel M, Kempf T, Schluter K, Willenbockel C, Brod T, Heineke J, et al. Conditional transgenic expression of fibroblast growth factor 9 in the adult mouse heart reduces heart failure mortality after myocardial infarction. Circulation. 2011;123:504-14 pubmed publisher
    b>Fibroblast growth factor 9 (FGF9) is secreted from bone marrow cells, which have been shown to improve systolic function after myocardial infarction (MI) in a clinical trial...
  15. Schmid S, Bieber M, Zhang F, Zhang M, He B, Jablons D, et al. Wnt and hedgehog gene pathway expression in serous ovarian cancer. Int J Gynecol Cancer. 2011;21:975-80 pubmed publisher
    ..and Obstetrics stage III serous ovarian cancer samples for expression of the Wnt pathway gene AXIN2, fibroblast growth factor 9, and Hh pathway gene expressions of glioma-associated oncogene 1, glioma-associated oncogene 2, patched ..
  16. Agrotis A, Kanellakis P, Kostolias G, Di Vitto G, Wei C, Hannan R, et al. Proliferation of neointimal smooth muscle cells after arterial injury. Dependence on interactions between fibroblast growth factor receptor-2 and fibroblast growth factor-9. J Biol Chem. 2004;279:42221-9 pubmed
    ..These studies demonstrate that, although multiple FGFRs are induced in neointimal SMCs following arterial injury, specific interactions between distinctly spliced FGFR-2 isoforms and FGF-9 contribute to the proliferation of these SMCs. ..
  17. DiNapoli L, Batchvarov J, Capel B. FGF9 promotes survival of germ cells in the fetal testis. Development. 2006;133:1519-27 pubmed
    ..FGF9 is necessary for 11.5 dpc XY gonocyte survival and is the earliest reported factor with a sex-specific role in regulating germ cell survival. ..
  18. Chi L, Itäranta P, Zhang S, Vainio S. Sprouty2 is involved in male sex organogenesis by controlling fibroblast growth factor 9-induced mesonephric cell migration to the developing testis. Endocrinology. 2006;147:3777-88 pubmed
    b>Fibroblast growth factor 9 (FGF9) signal has a role in organogenesis of the mammalian testis by controlling migration of mesonephric cells to the XY gonad, but neither it nor the FGF receptors is expressed sex-specifically...
  19. Kim Y, Kobayashi A, Sekido R, DiNapoli L, Brennan J, Chaboissier M, et al. Fgf9 and Wnt4 act as antagonistic signals to regulate mammalian sex determination. PLoS Biol. 2006;4:e187 pubmed
    ..We show through gain- and loss-of-function experiments that fibroblast growth factor 9 (FGF9) and WNT4 act as opposing signals to regulate sex determination...
  20. Popovici C, Conchonaud F, Birnbaum D, Roubin R. Functional phylogeny relates LET-756 to fibroblast growth factor 9. J Biol Chem. 2004;279:40146-52 pubmed
    ..This non-classical mode of secretion using an internal motif is conserved throughout evolution. ..
  21. Schreiber N, Spicer L. Effects of fibroblast growth factor 9 (FGF9) on steroidogenesis and gene expression and control of FGF9 mRNA in bovine granulosa cells. Endocrinology. 2012;153:4491-501 pubmed publisher
  22. Schreiber N, Totty M, Spicer L. Expression and effect of fibroblast growth factor 9 in bovine theca cells. J Endocrinol. 2012;215:167-75 pubmed publisher
    b>Fibroblast growth factor 9 (FGF9) protein affects granulosa cell (GC) function but is mostly localized to theca cell (TC) and stromal cell of rat ovaries...
  23. Zhang X, Stappenbeck T, White A, Lavine K, Gordon J, Ornitz D. Reciprocal epithelial-mesenchymal FGF signaling is required for cecal development. Development. 2006;133:173-80 pubmed
    ..Thus, these data add to our understanding of FGF-mediated reciprocal epithelial-mesenchymal signaling. ..
  24. Coffey E, Newman D, Sannes P. Expression of fibroblast growth factor 9 in normal human lung and idiopathic pulmonary fibrosis. J Histochem Cytochem. 2013;61:671-9 pubmed publisher
    ..The cellular distribution and established biologic activity of FGF9 make it a potentially strong candidate for contributing to the progression of IPF. ..
  25. Harada M, Murakami H, Okawa A, Okimoto N, Hiraoka S, Nakahara T, et al. FGF9 monomer-dimer equilibrium regulates extracellular matrix affinity and tissue diffusion. Nat Genet. 2009;41:289-98 pubmed publisher
    ..We propose a mechanism in which the range of FGF9 signaling in developing tissues is limited by its ability to homodimerize and its affinity for extracellular matrix heparan sulfate proteoglycans. ..
  26. Garofalo S, Kliger Spatz M, Cooke J, Wolstin O, Lunstrum G, Moshkovitz S, et al. Skeletal dysplasia and defective chondrocyte differentiation by targeted overexpression of fibroblast growth factor 9 in transgenic mice. J Bone Miner Res. 1999;14:1909-15 pubmed
  27. Geske M, Zhang X, Patel K, Ornitz D, Stappenbeck T. Fgf9 signaling regulates small intestinal elongation and mesenchymal development. Development. 2008;135:2959-68 pubmed publisher
    ..Taken together, the interaction of FGF and TGFbeta signaling pathways in the intestinal mesenchyme could represent novel targets for future short bowel syndrome therapies. ..
  28. Plotnikov A, Eliseenkova A, Ibrahimi O, Shriver Z, Sasisekharan R, Lemmon M, et al. Crystal structure of fibroblast growth factor 9 reveals regions implicated in dimerization and autoinhibition. J Biol Chem. 2001;276:4322-9 pubmed
    ..Thus, we propose an autoinhibitory mechanism for FGF9 that is dependent on sequences outside of the beta-trefoil core. Moreover, a model is presented providing a molecular basis for the preferential affinity of FGF9 toward FGFR3. ..
  29. Hecht H, Adar R, Hofmann B, Bogin O, Weich H, Yayon A. Structure of fibroblast growth factor 9 shows a symmetric dimer with unique receptor- and heparin-binding interfaces. Acta Crystallogr D Biol Crystallogr. 2001;57:378-84 pubmed
    ..The potential heparin-binding sites are in a pattern distinct from FGF1 and FGF2. The carbohydrate moiety attached at Asn79 has no structural influence. ..
  30. Huang J, Chuang J. Fibroblast growth factor 9 upregulates heme oxygenase-1 and gamma-glutamylcysteine synthetase expression to protect neurons from 1-methyl-4-phenylpyridinium toxicity. Free Radic Biol Med. 2010;49:1099-108 pubmed publisher
    ..Our previous studies found that fibroblast growth factor 9 (FGF9) prevented 1-methyl-4-phenylpyridinium (MPP(+))-induced nigral dopaminergic neuron death and was ..
  31. Piprek R. Genetic mechanisms underlying male sex determination in mammals. J Appl Genet. 2009;50:347-60 pubmed publisher
    ..Sertoli cells orchestrate testicular differentiation. In the absence of Sry, the predomination of the female pathway results in the realization of a robust genetic program that drives ovarian differentiation. ..
  32. Yin Y, Betsuyaku T, Garbow J, Miao J, Govindan R, Ornitz D. Rapid induction of lung adenocarcinoma by fibroblast growth factor 9 signaling through FGF receptor 3. Cancer Res. 2013;73:5730-41 pubmed publisher
  33. Lin Y, Tsai C, Chung C, Chen P, Sun H, Tsai S, et al. Fibroblast growth factor 9 stimulates steroidogenesis in postnatal Leydig cells. Int J Androl. 2010;33:545-53 pubmed publisher
    b>Fibroblast growth factor 9 (FGF9) is a potent mitogen and survival factor required for morphogenesis during embryonic development and numerous biological functions at adulthood...
  34. Huang J, Hong Y, Chuang J. Fibroblast growth factor 9 prevents MPP+-induced death of dopaminergic neurons and is involved in melatonin neuroprotection in vivo and in vitro. J Neurochem. 2009;109:1400-12 pubmed publisher
    ..b>Fibroblast growth factor 9 (FGF9) is a survival factor for various cell types; however, the effect of FGF9 on DA neurons has not ..
  35. Song J, Slack J. XFGF-9: a new fibroblast growth factor from Xenopus embryos. Dev Dyn. 1996;206:427-36 pubmed
    ..This supports the biochemical results, suggesting that the protein has at least some capacity to be secreted. ..
  36. Chen T, Kuo P, Hsu C, Tsai S, Chen M, Lin C, et al. Microsatellite in the 3' untranslated region of human fibroblast growth factor 9 (FGF9) gene exhibits pleiotropic effect on modulating FGF9 protein expression. Hum Mutat. 2007;28:98 pubmed
    b>Fibroblast growth factor 9 (FGF9) is a member of secreted polypeptide families and involved in many important biological processes, including implantation and morphogenesis during embryogenesis and adult life...
  37. Colvin J, White A, Pratt S, Ornitz D. Lung hypoplasia and neonatal death in Fgf9-null mice identify this gene as an essential regulator of lung mesenchyme. Development. 2001;128:2095-106 pubmed
    ..We suggest a model whereby FGF9 signaling from the epithelium and reciprocal FGF10 signaling from the mesenchyme coordinately regulate epithelial airway branching and organ size during lung embryogenesis. ..
  38. Hendrix N, Wu R, Kuick R, Schwartz D, Fearon E, Cho K. Fibroblast growth factor 9 has oncogenic activity and is a downstream target of Wnt signaling in ovarian endometrioid adenocarcinomas. Cancer Res. 2006;66:1354-62 pubmed
    ..Our findings support the notion that FGF9 is a key factor contributing to the cancer phenotype of OEAs carrying Wnt/beta-catenin pathway defects. ..
  39. Kinkl N, Ruiz J, Vecino E, Frasson M, Sahel J, Hicks D. Possible involvement of a fibroblast growth factor 9 (FGF9)-FGF receptor-3-mediated pathway in adult pig retinal ganglion cell survival in vitro. Mol Cell Neurosci. 2003;23:39-53 pubmed
    ..Taken together, these data suggest that the ligand-receptor couple FGF9-FGFR-3 may function to promote survival of adult mammalian RGC, and their application might be beneficial in retinal degenerative diseases such as glaucoma. ..
  40. Zhao S, Hung F, Colvin J, White A, Dai W, Lovicu F, et al. Patterning the optic neuroepithelium by FGF signaling and Ras activation. Development. 2001;128:5051-60 pubmed
    ..In mouse embryos lacking FGF9, the retinal pigment epithelium extends into the presumptive neural retina, indicating a role of FGF9 in defining the boundary of the neural retina. ..
  41. White A, Lavine K, Ornitz D. FGF9 and SHH regulate mesenchymal Vegfa expression and development of the pulmonary capillary network. Development. 2007;134:3743-52 pubmed
    ..Here, we show that fibroblast growth factor 9 (FGF9) and sonic hedgehog (SHH) signaling to lung mesenchyme, but not to endothelial cells, are each ..
  42. Behr B, Leucht P, Longaker M, Quarto N. Fgf-9 is required for angiogenesis and osteogenesis in long bone repair. Proc Natl Acad Sci U S A. 2010;107:11853-8 pubmed publisher
    ..Moreover, this study further supports the embryonic phenotype previously observed in the developing limb, thus promoting the concept that healing processes in adult organisms may recapitulate embryonic skeletal development. ..
  43. Bowles J, Feng C, Spiller C, Davidson T, Jackson A, Koopman P. FGF9 suppresses meiosis and promotes male germ cell fate in mice. Dev Cell. 2010;19:440-9 pubmed publisher
    ..Using in vitro and in vivo models, we demonstrate that fibroblast growth factor 9 (FGF9) produced in the fetal testis acts directly on germ cells to inhibit meiosis; in addition, FGF9 ..
  44. Schmahl J, Kim Y, Colvin J, Ornitz D, Capel B. Fgf9 induces proliferation and nuclear localization of FGFR2 in Sertoli precursors during male sex determination. Development. 2004;131:3627-36 pubmed
    ..The nuclear localization of FGFR2 coincides with the initiation of Sry expression and the nuclear localization of SOX9 during the early differentiation of Sertoli cells and the determination of male fate. ..
  45. Frontini M, Nong Z, Gros R, Drangova M, O Neil C, Rahman M, et al. Fibroblast growth factor 9 delivery during angiogenesis produces durable, vasoresponsive microvessels wrapped by smooth muscle cells. Nat Biotechnol. 2011;29:421-7 pubmed publisher
    ..Using microarray expression analysis, we discovered that fibroblast growth factor 9 (FGF9) was highly upregulated as human vascular smooth muscle cells (SMCs) assemble into layered cords...
  46. Wu X, Jin C, Wang F, Yu C, McKeehan W. Stromal cell heterogeneity in fibroblast growth factor-mediated stromal-epithelial cell cross-talk in premalignant prostate tumors. Cancer Res. 2003;63:4936-44 pubmed
    ..Epithelium-dependent control of a stromal cell phenotype within a tumor may be a determinant of whether tumors remain in nonmalignant homeostasis or progress to malignancy. ..
  47. Hecht D, Zimmerman N, Bedford M, Avivi A, Yayon A. Identification of fibroblast growth factor 9 (FGF9) as a high affinity, heparin dependent ligand for FGF receptors 3 and 2 but not for FGF receptors 1 and 4. Growth Factors. 1995;12:223-33 pubmed
    ..In conclusion FGF9 presents a unique case of ligand-receptor specificity and fulfills the criteria as a high affinity, heparin-dependent ligand for FGFR3. ..
  48. Yang H, Fang F, Chang R, Yang L. MicroRNA-140-5p suppresses tumor growth and metastasis by targeting transforming growth factor ? receptor 1 and fibroblast growth factor 9 in hepatocellular carcinoma. Hepatology. 2013;58:205-17 pubmed publisher
    ..TGFB receptor 1 (TGFBR1) and fibroblast growth factor 9 (FGF9) were then characterized as the direct targets for miR-140-5p after it was found that ectopic miR-..
  49. Hajihosseini M, Heath J. Expression patterns of fibroblast growth factors-18 and -20 in mouse embryos is suggestive of novel roles in calvarial and limb development. Mech Dev. 2002;113:79-83 pubmed
  50. Chen T, Hsu C, Tsai S, Sun H. AUF1 p42 isoform selectively controls both steady-state and PGE2-induced FGF9 mRNA decay. Nucleic Acids Res. 2010;38:8061-71 pubmed publisher
    b>Fibroblast growth factor 9 (FGF9) is an autocrine/paracrine growth factor that plays vital roles in many physiologic processes including embryonic development...
  51. Hung I, Yu K, Lavine K, Ornitz D. FGF9 regulates early hypertrophic chondrocyte differentiation and skeletal vascularization in the developing stylopod. Dev Biol. 2007;307:300-13 pubmed
    ..In developing stylopod elements, FGF9 promotes chondrocyte hypertrophy at early stages and regulates vascularization of the growth plate and osteogenesis at later stages of skeletal development. ..
  52. Yi L, Domyan E, Lewandoski M, Sun X. Fibroblast growth factor 9 signaling inhibits airway smooth muscle differentiation in mouse lung. Dev Dyn. 2009;238:123-37 pubmed publisher
    ..In this study, we test the hypothesis that fibroblast growth factor 9 (Fgf9) signaling is essential to restrict SMC differentiation to the proximal lung...
  53. Lum M, Turbic A, Mitrovic B, Turnley A. Fibroblast growth factor-9 inhibits astrocyte differentiation of adult mouse neural progenitor cells. J Neurosci Res. 2009;87:2201-10 pubmed publisher
    ..FGF9 therefore has multiple effects on adult neural precursor cell function, enhancing neuronal precursor proliferation and specifically inhibiting GFAP expression. ..