Genomes and Genes
Gene Symbol: Fgf9
Description: fibroblast growth factor 9
Alias: Eks, fibroblast growth factor 9, FGF-9, GAF, HBGF-9, elbow knee synostosis, glia-activating factor
- 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 pubmedb>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...
- 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
- Michos O, Panman L, Vintersten K, Beier K, Zeller R, Zuniga A. Gremlin-mediated BMP antagonism induces the epithelial-mesenchymal feedback signaling controlling metanephric kidney and limb organogenesis. Development. 2004;131:3401-10 pubmed..As a consequence, the metanephric mesenchyme is eliminated by apoptosis, in the same way as the core mesenchymal cells of the limb bud. ..
- Bagheri Fam S, Sim H, Bernard P, Jayakody I, Taketo M, Scherer G, et al. Loss of Fgfr2 leads to partial XY sex reversal. Dev Biol. 2008;314:71-83 pubmed..the XY gonad, presumptive Sertoli cells begin to differentiate when SRY up-regulates SOX9, which in turn activates FGF9 and PGDS to maintain its own expression...
- 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..We report that FGF9 is normally expressed in the distal region of the optic vesicle that is destined to become the neural retina, ..
- 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..Here we identify Fgf9 as a second FGF ligand that is critical for skeletal development...
- Nie X. Apoptosis, proliferation and gene expression patterns in mouse developing tongue. Anat Embryol (Berl). 2005;210:125-32 pubmed..Fgf2 was seen in the tongue muscles at the late embryonic and postnatal stages. These results suggest that Bmp and Fgf signalling regulates tongue development at multiple stages, possibly related to proliferation and differentiation. ..
- 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..We show here that, during the precartilage and cartilage stages, Fgf9 is expressed in specific nonsensory domains of the otic epithelium and its receptors, Fgfr1(IIIc) and Fgfr2(IIIc), ..
- Moniot B, Declosmenil F, Barrionuevo F, Scherer G, Aritake K, Malki S, et al. The PGD2 pathway, independently of FGF9, amplifies SOX9 activity in Sertoli cells during male sexual differentiation. Development. 2009;136:1813-21 pubmed publisher..In the mouse XY gonad, SOX9 upregulates Fgf9, which initiates a Sox9/Fgf9 feedforward loop, and Sox9 expression is stimulated by the prostaglandin D2 (PGD2) ..
- Weaver M, Batts L, Hogan B. Tissue interactions pattern the mesenchyme of the embryonic mouse lung. Dev Biol. 2003;258:169-84 pubmed..zone correlates with the presence of an overlying mesothelial layer, which, as in vivo, expresses Fibroblast Growth Factor 9 (Fgf9)...
- 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...
- 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..However, no FGF has been shown to regulate lung mesenchyme. In embryonic lung, Fgf9 is detected in airway epithelium and visceral pleura at E10.5, but is restricted to the pleura by E12.5...
- Mariani F, Ahn C, Martin G. Genetic evidence that FGFs have an instructive role in limb proximal-distal patterning. Nature. 2008;453:401-5 pubmed publisher..Fibroblast growth factor (FGF) gene family members are key AER-derived signals, with Fgf4, Fgf8, Fgf9 and Fgf17 expressed specifically in the mouse AER...
- Klein O, Lyons D, Balooch G, Marshall G, Basson M, Peterka M, et al. An FGF signaling loop sustains the generation of differentiated progeny from stem cells in mouse incisors. Development. 2008;135:377-85 pubmed..These data reveal that the generation of differentiated progeny from a particular stem cell population can be differently regulated in the embryo and adult. ..
- Ottolenghi C, Omari S, Garcia Ortiz J, Uda M, Crisponi L, Forabosco A, et al. Foxl2 is required for commitment to ovary differentiation. Hum Mol Genet. 2005;14:2053-62 pubmed..This suggests the possible continued involvement of sex-determining genes in maintaining ovarian function throughout female reproductive life. ..
- Mailleux A, Tefft D, Ndiaye D, Itoh N, Thiery J, Warburton D, et al. Evidence that SPROUTY2 functions as an inhibitor of mouse embryonic lung growth and morphogenesis. Mech Dev. 2001;102:81-94 pubmed..These results indicate for the first time that mSPROUTY2 functions as a negative regulator of embryonic lung morphogenesis and growth. ..
- Liu C, Bingham N, Parker K, Yao H. Sex-specific roles of beta-catenin in mouse gonadal development. Hum Mol Genet. 2009;18:405-17 pubmed publisher..Our results demonstrate that beta-catenin is responsible for transducing sex-specific signals in the SF1-positive somatic cell population during mouse gonadal development. ..
- 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..Here we show that FGF9 and FGFR3, a high-affinity receptor for this ligand, have similar developmental expression patterns, particularly ..
- 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 publisherb>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...
- Gregoire E, Lavery R, Chassot A, Akiyama H, Treier M, Behringer R, et al. Transient development of ovotestes in XX Sox9 transgenic mice. Dev Biol. 2011;349:65-77 pubmed publisher..Finally, ovarian cells of the XX Wt1:Sox9 ovotestis undergo apoptosis during late embryogenesis leading to complete female-to-male sex reversal of the transgenic mice at birth...
- Murakami H, Okawa A, Yoshida H, Nishikawa S, Moriya H, Koseki H. Elbow knee synostosis (Eks): a new mutation on mouse Chromosome 14. Mamm Genome. 2002;13:341-4 pubmed
- 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..Interestingly, FGF9, a growth factor crucial for sex differentiation and survival of fetal gonocytes, upregulates levels of NANOS2 in ..
- 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..Here we describe the cloning and expression of the mouse homologue of FGF9, and the use of a panel of soluble FGF receptors and genetically engineered cells to study its receptor binding ..
- White A, Xu J, Yin Y, Smith C, Schmid G, Ornitz D. FGF9 and SHH signaling coordinate lung growth and development through regulation of distinct mesenchymal domains. Development. 2006;133:1507-17 pubmed..In previous studies, we have shown that FGF9 signals are essential for lung mesenchyme development...
- 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 ..
- 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 pubmedRecently, we demonstrated that loss of Fgf9 results in a block of testis development and a male to female sex-reversed phenotype; however, the function of Fgf9 in sex determination was unknown...
- Brennan J, Capel B. One tissue, two fates: molecular genetic events that underlie testis versus ovary development. Nat Rev Genet. 2004;5:509-21 pubmed
- Wilhelm D, Martinson F, Bradford S, Wilson M, Combes A, Beverdam A, et al. Sertoli cell differentiation is induced both cell-autonomously and through prostaglandin signaling during mammalian sex determination. Dev Biol. 2005;287:111-24 pubmed..Our data indicate a mechanism whereby Sry uses both a cell-autonomous mechanism and a PGD2-mediated signaling mechanism to stimulate expression of Sox9 and induce the differentiation of Sertoli cells in vivo. ..
- 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 pubmedMesothelial Fibroblast Growth Factor 9 (Fgf9) has been demonstrated by inactivation studies in mouse to be critical for the proliferation of the mesenchyme...
- Colvin J, Feldman B, Nadeau J, Goldfarb M, Ornitz D. Genomic organization and embryonic expression of the mouse fibroblast growth factor 9 gene. Dev Dyn. 1999;216:72-88 pubmedb>Fibroblast growth factor 9 (FGF9), originally cloned as glial-activating factor from human glioma cells, is expressed in adult rat brain and kidney...
- 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...
- DiNapoli L, Batchvarov J, Capel B. FGF9 promotes survival of germ cells in the fetal testis. Development. 2006;133:1519-27 pubmedIn addition to its role in somatic cell development in the testis, our data have revealed a role for Fgf9 in XY germ cell survival. In Fgf9-null mice, germ cells in the XY gonad decline in numbers after 11...
- Sun X, Mariani F, Martin G. Functions of FGF signalling from the apical ectodermal ridge in limb development. Nature. 2002;418:501-8 pubmed..In the complete absence of both FGF4 and FGF8 activities, limb development fails. We present a model to explain how the mutant phenotypes arise from FGF-mediated effects on limb bud size and cell survival. ..
- Gay D, Kwon O, Zhang Z, Spata M, Plikus M, Holler P, et al. Fgf9 from dermal ?? T cells induces hair follicle neogenesis after wounding. Nat Med. 2013;19:916-23 pubmed publisher..Here we show that fibroblast growth factor 9 (Fgf9), initially secreted by ?? T cells, modulates hair follicle regeneration after wounding the skin ..
- Kim H, Rice D, Kettunen P, Thesleff I. FGF-, BMP- and Shh-mediated signalling pathways in the regulation of cranial suture morphogenesis and calvarial bone development. Development. 1998;125:1241-51 pubmed..b>Fgf9 was expressed throughout the calvarial mesenchyme, the dura mater, the developing bones and the overlying skin, but ..
- Chassot A, Ranc F, Gregoire E, Roepers Gajadien H, Taketo M, Camerino G, et al. Activation of beta-catenin signaling by Rspo1 controls differentiation of the mammalian ovary. Hum Mol Genet. 2008;17:1264-77 pubmed publisher..Thus, a balance between Sox9 and beta-catenin activation determines the fate of the gonad, with Rspo1 acting as a crucial regulator of canonical beta-catenin signaling required for female development. ..
- Hrabe de Angelis M, Flaswinkel H, Fuchs H, Rathkolb B, Soewarto D, Marschall S, et al. Genome-wide, large-scale production of mutant mice by ENU mutagenesis. Nat Genet. 2000;25:444-7 pubmed..Our mutant lines are freely accessible to non-commercial users (for information, see http://www.gsf.de/ieg/groups/enu-mouse.html). ..
- Lin Y, Chen L, Lin C, Luo Y, Tsai R, Wang F. Neuron-derived FGF9 is essential for scaffold formation of Bergmann radial fibers and migration of granule neurons in the cerebellum. Dev Biol. 2009;329:44-54 pubmed publisherAlthough fibroblast growth factor 9 (FGF9) is widely expressed in the central nervous system (CNS), the function of FGF9 in neural development remains undefined...
- Peters H, Balling R. Teeth. Where and how to make them. Trends Genet. 1999;15:59-65 pubmed..This cascade provides a molecular model by which reciprocal tissue interactions are controlled. ..
- 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 publisherThe spontaneous dominant mouse mutant, Elbow knee synostosis (Eks), shows elbow and knee joint synosotsis, and premature fusion of cranial sutures...
- Huang Y, Jin C, Hamana T, Liu J, Wang C, An L, et al. Overexpression of FGF9 in prostate epithelial cells augments reactive stroma formation and promotes prostate cancer progression. Int J Biol Sci. 2015;11:948-60 pubmed publisherBone metastasis is the major cause of morbidity and mortality of prostate cancer (PCa). Fibroblast growth factor 9 (FGF9) has been reported to promote PCa bone metastasis...
- Arman E, Haffner Krausz R, Gorivodsky M, Lonai P. Fgfr2 is required for limb outgrowth and lung-branching morphogenesis. Proc Natl Acad Sci U S A. 1999;96:11895-9 pubmed..Possible epithelial-mesenchymal interactions between the splicing alternatives of Fgfr2 and their specific ligands will be discussed. ..
- Wright T, Hatch E, Karabagli H, Karabagli P, Schoenwolf G, Mansour S. Expression of mouse fibroblast growth factor and fibroblast growth factor receptor genes during early inner ear development. Dev Dyn. 2003;228:267-72 pubmed..Fgf16 was expressed in the posterior otic cup and vesicle, suggesting roles in otic cell fate decisions and/or axis formation. ..
- Vanhoutteghem A, Messiaen S, Hervé F, Delhomme B, Moison D, Petit J, et al. The zinc-finger protein basonuclin 2 is required for proper mitotic arrest, prevention of premature meiotic initiation and meiotic progression in mouse male germ cells. Development. 2014;141:4298-310 pubmed publisher..In view of the extreme evolutionary conservation of BNC2, the findings described here are likely to apply to many species. ..
- Combes A, Bowles J, Feng C, Chiu H, Khoo P, Jackson A, et al. Expression and functional analysis of Dkk1 during early gonadal development. Sex Dev. 2011;5:124-30 pubmed publisher..Nor did we find significant differences in expression of key markers of testis and ovarian development. We propose that DKK1 may play a protective role that is not unmasked by loss-of-function in the absence of other stressors. ..
- Barak H, Huh S, Chen S, Jeanpierre C, Martinovic J, Parisot M, et al. FGF9 and FGF20 maintain the stemness of nephron progenitors in mice and man. Dev Cell. 2012;22:1191-207 pubmed publisher..Here we provide evidence that Fgf20 and Fgf9, expressed in the niche, and Fgf9, secreted from the adjacent ureteric bud, are necessary and sufficient to ..
- Tucker A, Al Khamis A, Ferguson C, Bach I, Rosenfeld M, Sharpe P. Conserved regulation of mesenchymal gene expression by Fgf-8 in face and limb development. Development. 1999;126:221-8 pubmed..Regulation of gene expression by Fgf8 in association with CD44 is thus conserved between limb and mandibular arch development. ..
- Mansour S, Li C, Urness L. Genetic rescue of Muenke syndrome model hearing loss reveals prolonged FGF-dependent plasticity in cochlear supporting cell fates. Genes Dev. 2013;27:2320-31 pubmed publisher..This property might be exploited for the regulation of sensory cell regeneration from support cells. ..
- SINGLA D, Wang J. Fibroblast Growth Factor-9 Activates c-Kit Progenitor Cells and Enhances Angiogenesis in the Infarcted Diabetic Heart. Oxid Med Cell Longev. 2016;2016:5810908 pubmed publisher..Overall, our data suggests FGF-9 has the potential to attenuate vascular cell apoptosis, activate c-Kit progenitor cells, and enhance angiogenesis and neovascularization in C57BL/6 and db/db mice leading to improved cardiac function. ..
- Muthukrishnan S, Yang X, Friesel R, Oxburgh L. Concurrent BMP7 and FGF9 signalling governs AP-1 function to promote self-renewal of nephron progenitor cells. Nat Commun. 2015;6:10027 pubmed publisher..While JUN is regulated by BMP7, we find that its partner FOS is regulated by FGF9. We demonstrate that BMP7 and FGF9 coordinately regulate AP-1 transcription to promote G1-S cell cycle progression ..
- Muenke M, Schell U. Fibroblast-growth-factor receptor mutations in human skeletal disorders. Trends Genet. 1995;11:308-13 pubmed..Comparison of these specific mutations with the resulting phenotypes is now providing new insight into the role of these receptors in normal and abnormal bone development. ..
- Mattei M, De Moerlooze L, Lovec H, Coulier F, Birnbaum D, Dickson C. Mouse fgf9 (fibroblast growth factor 9) is localized on chromosome 14. Mamm Genome. 1997;8:617-8 pubmed
- Huang H, Yang X, Bao M, Cao H, Miao X, Zhang X, et al. Ablation of the Sox11 Gene Results in Clefting of the Secondary Palate Resembling the Pierre Robin Sequence. J Biol Chem. 2016;291:7107-18 pubmed publisher..Extensive analyses of gene expression inSox11 deficiency identified FGF9 as a potential candidate target of Sox11 in the modulation of cell proliferation both in the mandible and the ..
- Puk O, Moller G, Geerlof A, Krowiorz K, Ahmad N, Wagner S, et al. The pathologic effect of a novel neomorphic Fgf9(Y162C) allele is restricted to decreased vision and retarded lens growth. PLoS ONE. 2011;6:e23678 pubmed publisher..Among the Fgf pathway ligands, Fgf9 (UniProt: P54130) has been demonstrated to participate in maturation of various organs and tissues including ..
- Lee J, Yu Q, Shin J, Sebzda E, Bertozzi C, Chen M, et al. Klf2 is an essential regulator of vascular hemodynamic forces in vivo. Dev Cell. 2006;11:845-57 pubmed..These findings identify Klf2 as an essential hemodynamic regulator in vivo and suggest that hemodynamic regulation in response to fluid shear stress is required for cardiovascular development and function. ..
- Yin Y, Castro A, Hoekstra M, Yan T, Kanakamedala A, Dehner L, et al. Fibroblast Growth Factor 9 Regulation by MicroRNAs Controls Lung Development and Links DICER1 Loss to the Pathogenesis of Pleuropulmonary Blastoma. PLoS Genet. 2015;11:e1005242 pubmed publisher..b>Fibroblast Growth Factor 9 (FGF9) is expressed in the mesothelium and epithelium during lung development and primarily functions to ..
- Lavery R, Lardenois A, Ranc Jianmotamedi F, Pauper E, Gregoire E, Vigier C, et al. XY Sox9 embryonic loss-of-function mouse mutants show complete sex reversal and produce partially fertile XY oocytes. Dev Biol. 2011;354:111-22 pubmed publisher..Taken together, we found that XY Sf1:Cre(Tg/+); Sox9(flox/flox) females are capable of producing viable offspring albeit at a reduced level. ..
- Fujimoto Y, Tanaka S, Yamaguchi Y, Kobayashi H, Kuroki S, Tachibana M, et al. Homeoproteins Six1 and Six4 regulate male sex determination and mouse gonadal development. Dev Cell. 2013;26:416-30 pubmed publisher..The regulation of Fog2 induces Sry expression in male sex determination, and the regulation of Nr5a1 in gonadal precursor formation determines gonadal size. ..
- Chassot A, Gregoire E, Lavery R, Taketo M, de Rooij D, Adams I, et al. RSPO1/?-catenin signaling pathway regulates oogonia differentiation and entry into meiosis in the mouse fetal ovary. PLoS ONE. 2011;6:e25641 pubmed publisher..Our results demonstrate that RSPO1/?-catenin signaling is involved in meiosis in fetal germ cells and contributes to the cellular decision of germ cells to differentiate into oocyte or sperm...
- Lauriol J, Cabrera J, Roy A, Keith K, Hough S, Damilano F, et al. Developmental SHP2 dysfunction underlies cardiac hypertrophy in Noonan syndrome with multiple lentigines. J Clin Invest. 2016;126:2989-3005 pubmed publisher..Together, our data provide functional and disease-based evidence that aberrant SHP2 signaling during cardiac development leads to CHD and adult-onset heart hypertrophy. ..