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Gene Review

fgfr1-b  -  fibroblast growth factor receptor 1

Xenopus laevis

Synonyms: XFGFR-1, bfgfr, cek, fgfr-1, fgfr1, ...
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Disease relevance of X1FGFR


High impact information on X1FGFR


Biological context of X1FGFR

  • Overexpression of Xenopus FGF receptor protein by transfection of COS1 cells with the corresponding cDNA in a transient expression vector leads to the appearance of new FGF binding sites on transfected cells, consistent with these cDNAs encoding for FGF receptors [5].
  • RNase protection analysis revealed that both VT- and VT+ forms of the FGFR1 were expressed throughout embryonic development, the VT+ being the major form [6].
  • In addition, we identified a region in the cytoplasmic tail of ephrin B1 that is critical for interaction with the FGF receptor; we also report FGF-induced phosphorylation of ephrins in a neural tissue [7].
  • This is the first demonstration of communication between the FGF receptor family and the Eph ligand family and implicates cross talk between these two cell surface molecules in regulating cell adhesion [7].
  • To examine whether N-cadherin and FGFRs share the same pathway or use distinct second messenger pathways, specific inhibitors of implicated signaling molecules were added to neurons stimulated by N-cadherin, basic fibroblast growth factor (bFGF), or brain-derived nerve factor (BDNF) (which stimulates RGC outgrowth by a FGFR-independent mechanism) [8].

Anatomical context of X1FGFR

  • When blastula-stage ectoderm is cultured in control amphibian salt solutions, Xenopus FGF receptor mRNA declines to undetectable levels by late neurula stages [5].
  • A cDNA clone, predicted to encode a variant form of the type 1 fibroblast growth factor receptor (FGFR1) containing a dipeptide Val-Thr (VT) deletion at amino acid positions 423 and 424 located within the juxtamembrane region, was isolated from a Xenopus embryo (stage 8 blastula) library [6].
  • Fibroblast growth factor receptor blockade results in almost a 50% loss of photoreceptors and amacrine cells, and a concurrent 3.5-fold increase in Müller glia, suggesting a shift towards a Müller cell fate in the absence of a fibroblast growth factor receptor signal [9].
  • The VT+ and VT- isoforms of the fibroblast growth factor receptor type 1 are differentially expressed in the presumptive mesoderm of Xenopus embryos and differ in their ability to mediate mesoderm formation [10].
  • The implications of our findings for the evolutionarily conserved role of the FGFR pathway in the functions of Spemann's organizer and other vertebrate-signaling centers are discussed [11].

Associations of X1FGFR with chemical compounds

  • These results suggest that the ventral regionalization of the eye is specified by interactions of Hh, RA and FGFR signaling [12].
  • However, blocking experiments with a dominant-inhibitory FGF receptor and a dominant-inhibitory retinoic acid receptor suggest that Pax-3 inductive activities arising from Hensen's node and posterior non-axial mesoderm do not strictly depend on FGF or retinoic acid [13].
  • Dorsoventral patterning of the Xenopus eye: a collaboration of Retinoid, Hedgehog and FGF receptor signaling [12].
  • Members of the Src family of non-receptor tyrosine kinases play a critical role in mesoderm formation in the frog, Xenopus laevis, acting as required mediators downstream of the fibroblast growth factor receptor [14].
  • The use of the PLCgamma inhibitory peptide, neomycin and the calcium chelator BAPTA-AM on oocytes expressing FGFR1 or the stimulation by PDGF-BB of oocytes expressing PDGFR-FGFR1 mutated on the PLCgamma binding site, prevented GVBD and ERK2 phosphorylation [15].

Physical interactions of X1FGFR

  • Furthermore, we show that three additional phosphotyrosylproteins from the FGFR1 complex specifically bound to the adaptor molecule Nck [16].

Regulatory relationships of X1FGFR

  • Blocking the endogenous FGF signal with a dominant negative FGF receptor (XFD) mainly inhibited development of posterior neural tissue in neuralized ACs [17].
  • Likewise, Xmc expression can be induced by ectopic XeFGF signaling and the early mesodermal expression is dependent on FGF receptor-mediated signaling [18].

Other interactions of X1FGFR

  • Finally, XLPTP1 physically associates only with an activated FGFR1, and this interaction requires the presence of SNT1/FRS-2 (FGFR substrate 2) [19].
  • We show by loss of function analysis that Xnr3 activates Xbra expression through FGFR1 [20].
  • We expressed the XFGFR-2 cDNA in COS1 cells and showed that it functions as an FGF receptor by binding radiolabeled FGF-2 [21].
  • We provide evidence that FGFR-1 and FGFR-4 signals elicit distinct responses both in naive and neuralized ectodermal cells [22].
  • Overexpression of the dominant-negative FGF receptor (XFD) in Keller explants inhibited the posterior neural markers En-2, Krox-20, and HoxB9, but not the panneural marker nrp-1 and the anterior neurectodermal markers XAG-1 and Xotx-2 [23].

Analytical, diagnostic and therapeutic context of X1FGFR

  • Sequence analysis of genomic DNA encoding a portion of the FGFR1 juxtamembrane region demonstrated that this variant form arises from use of an alternative 5' splice donor site [6].
  • In co-immunoprecipitation assays, the intracellular domain of Sef interacts with FGF receptors, FGFR1 and FGFR2 [24].
  • We used cDNA microarray analysis to screen for FGF target genes in Xenopus embryos treated with the FGFR1 inhibitor SU5402, and identified neurotrophin receptor homolog (NRH) as an FGF target [25].
  • Third, using whole-mount in situ hybridization, we show that XFGFR-1, XFGFR-2, and XFGFR-4 are expressed in dramatically different patterns, arguing that specific FGF signaling events are mediated by different members of the FGFR family [26].


  1. SNT1/FRS2 mediates germinal vesicle breakdown induced by an activated FGF receptor1 in Xenopus oocytes. Mood, K., Friesel, R., Daar, I.O. J. Biol. Chem. (2002) [Pubmed]
  2. The identification of two novel ligands of the FGF receptor by a yeast screening method and their activity in Xenopus development. Kinoshita, N., Minshull, J., Kirschner, M.W. Cell (1995) [Pubmed]
  3. Expression of a dominant negative mutant of the FGF receptor disrupts mesoderm formation in Xenopus embryos. Amaya, E., Musci, T.J., Kirschner, M.W. Cell (1991) [Pubmed]
  4. Inhibition of FGF receptor activity in retinal ganglion cell axons causes errors in target recognition. McFarlane, S., Cornel, E., Amaya, E., Holt, C.E. Neuron (1996) [Pubmed]
  5. cDNA cloning and developmental expression of fibroblast growth factor receptors from Xenopus laevis. Friesel, R., Dawid, I.B. Mol. Cell. Biol. (1991) [Pubmed]
  6. Cloning of a fibroblast growth factor receptor 1 splice variant from Xenopus embryos that lacks a protein kinase C site important for the regulation of receptor activity. Gillespie, L.L., Chen, G., Paterno, G.D. J. Biol. Chem. (1995) [Pubmed]
  7. Fibroblast growth factor receptor-mediated rescue of x-ephrin B1-induced cell dissociation in Xenopus embryos. Chong, L.D., Park, E.K., Latimer, E., Friesel, R., Daar, I.O. Mol. Cell. Biol. (2000) [Pubmed]
  8. Fibroblast growth factor receptor signaling in Xenopus retinal axon extension. Lom, B., Höpker, V., McFarlane, S., Bixby, J.L., Holt, C.E. J. Neurobiol. (1998) [Pubmed]
  9. A role for the fibroblast growth factor receptor in cell fate decisions in the developing vertebrate retina. McFarlane, S., Zuber, M.E., Holt, C.E. Development (1998) [Pubmed]
  10. The VT+ and VT- isoforms of the fibroblast growth factor receptor type 1 are differentially expressed in the presumptive mesoderm of Xenopus embryos and differ in their ability to mediate mesoderm formation. Paterno, G.D., Ryan, P.J., Kao, K.R., Gillespie, L.L. J. Biol. Chem. (2000) [Pubmed]
  11. The FGFR pathway is required for the trunk-inducing functions of Spemann's organizer. Mitchell, T.S., Sheets, M.D. Dev. Biol. (2001) [Pubmed]
  12. Dorsoventral patterning of the Xenopus eye: a collaboration of Retinoid, Hedgehog and FGF receptor signaling. Lupo, G., Liu, Y., Qiu, R., Chandraratna, R.A., Barsacchi, G., He, R.Q., Harris, W.A. Development (2005) [Pubmed]
  13. Expression of Pax-3 is initiated in the early neural plate by posteriorizing signals produced by the organizer and by posterior non-axial mesoderm. Bang, A.G., Papalopulu, N., Kintner, C., Goulding, M.D. Development (1997) [Pubmed]
  14. The molecular basis of Src kinase specificity during vertebrate mesoderm formation. Hama, J., Suri, C., Haremaki, T., Weinstein, D.C. J. Biol. Chem. (2002) [Pubmed]
  15. Signal transduction pathways triggered by fibroblast growth factor receptor 1 expressed in Xenopus laevis oocytes after fibroblast growth factor 1 addition. Role of Grb2, phosphatidylinositol 3-kinase, Src tyrosine kinase, and phospholipase Cgamma. Browaeys-Poly, E., Cailliau, K., Vilain, J.P. Eur. J. Biochem. (2000) [Pubmed]
  16. Identification of phosphorylated proteins associated with the fibroblast growth factor receptor type I during early Xenopus development. Ryan, P.J., Paterno, G.D., Gillespie, L.L. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  17. Studies on the role of fibroblast growth factor signaling in neurogenesis using conjugated/aged animal caps and dorsal ectoderm-grafted embryos. Xu, R.H., Kim, J., Taira, M., Sredni, D., Kung, H. J. Neurosci. (1997) [Pubmed]
  18. Xenopus marginal coil (Xmc), a novel FGF inducible cytosolic coiled-coil protein regulating gastrulation movements. Frazzetto, G., Klingbeil, P., Bouwmeester, T. Mech. Dev. (2002) [Pubmed]
  19. Low-molecular-weight protein tyrosine phosphatase is a positive component of the fibroblast growth factor receptor signaling pathway. Park, E.K., Warner, N., Mood, K., Pawson, T., Daar, I.O. Mol. Cell. Biol. (2002) [Pubmed]
  20. A novel role for a nodal-related protein; Xnr3 regulates convergent extension movements via the FGF receptor. Yokota, C., Kofron, M., Zuck, M., Houston, D.W., Isaacs, H., Asashima, M., Wylie, C.C., Heasman, J. Development (2003) [Pubmed]
  21. Spatially restricted expression of fibroblast growth factor receptor-2 during Xenopus development. Friesel, R., Brown, S.A. Development (1992) [Pubmed]
  22. Signaling specificities of fibroblast growth factor receptors in early Xenopus embryo. Umbhauer, M., Penzo-Méndez, A., Clavilier, L., Boucaut, J., Riou, J. J. Cell. Sci. (2000) [Pubmed]
  23. FGF is required for posterior neural patterning but not for neural induction. Holowacz, T., Sokol, S. Dev. Biol. (1999) [Pubmed]
  24. Identification of Sef, a novel modulator of FGF signalling. Tsang, M., Friesel, R., Kudoh, T., Dawid, I.B. Nat. Cell Biol. (2002) [Pubmed]
  25. FGF signal regulates gastrulation cell movements and morphology through its target NRH. Chung, H.A., Hyodo-Miura, J., Nagamune, T., Ueno, N. Dev. Biol. (2005) [Pubmed]
  26. Evolutionarily conserved and divergent expression of members of the FGF receptor family among vertebrate embryos, as revealed by FGFR expression patterns in Xenopus. Golub, R., Adelman, Z., Clementi, J., Weiss, R., Bonasera, J., Servetnick, M. Dev. Genes Evol. (2000) [Pubmed]
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