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Gene Review

FGFR1  -  fibroblast growth factor receptor 1

Gallus gallus

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Disease relevance of FGFR1

  • To investigate the effects of inactivation of FGFR on the growth of malignant gliomas, we constructed a replication-deficient recombinant adenovirus vector encoding a truncated form of chicken FGFR1 (AxCA delta FR) [1].
  • METHODS: Lenses were injected on embryonic day (E)3 with replication-defective retroviruses that express full-length or truncated FGF receptor (FGFR)-1 or a secreted form of FGF1 [2].

High impact information on FGFR1

  • Patterns of expression of transcripts encoding receptors for fibroblast growth factor and nerve growth factor (FGF-R and NGF-R) in the developing chick nervous system are compared using in situ hybridization histochemistry [3].
  • The pattern of NGF-R expression is generally reciprocal to that of FGF-R in the CNS and in some phases of development of the PNS [3].
  • These experiments provide in vivo evidence to support the hypothesis that regulation of FGF receptor levels may function as a mechanism for controlling FGF-dependent processes during embryonic development [4].
  • Because endogenous chick FGF may remain bound to FGF receptor in membrane preparations, membranes were treated with acidic (pH 4.0) buffers to release bound FGF; such treatment did not affect 125I-aFGF binding and moderately increased the number of binding sites in day-7 and -19 embryos [4].
  • Consequently, the observed loss of high affinity 125I-aFGF binding sites and FGF-binding polypeptides most likely represents a loss of FGF receptor protein [4].

Biological context of FGFR1

  • Differential expression of these FGF receptor genes suggested that differential roles of these receptors in epithelia-mesenchymal interactions of limb and feather morphogenesis [5].
  • Retina regeneration in the chick embryo is not induced by spontaneous Mitf downregulation but requires FGF/FGFR/MEK/Erk dependent upregulation of Pax6 [6].
  • We examined FGFR4 function during myogenesis, and we demonstrate that inhibition of FGFR4, but not FGFR1 signaling, leads to a dramatic loss of limb muscles [7].
  • These studies demonstrate that the FGFR1 promoter is activated by Sp transcription factors in proliferating myoblasts and demonstrate at least part of the mechanism by which FGFR1 gene expression is down-regulated in differentiated muscle fibers [8].
  • RESULTS: Lens fiber cell differentiation was not inhibited in cells infected with virus expressing truncated FGFR1 [2].

Anatomical context of FGFR1


Associations of FGFR1 with chemical compounds

  • In a previous study, we demonstrated that FGFR1 activity within the organizer is required for the production of both the somitic muscle- and pronephros-patterning signals by the organizer and the expression of chordin, an organizer-specific secreted protein (Mitchell and Sheets [2001] Dev. Biol. 237:295-305) [11].
  • Its amino acid sequence suggests that the Cek1 protein is a transmembrane tyrosine kinase and presumably the receptor for an unknown ligand [12].
  • The observed correlation between the level of FREK gene expression and various stages of differentiation, its modulation by b-FGF and RA, as well as the correlation between FREK gene expression and the physiological response to b-FGF, suggest that this specific FGF receptor plays an important role in muscle and cartilage cell differentiation [13].
  • This data suggests that retinoic acid may be affecting other aspects of the FGF receptor-ligand interaction [14].

Regulatory relationships of FGFR1

  • Ectopic Mitf expression was able to inhibit transdifferentiation by acting downstream of FGFR/MEK/Erk signaling, likely by inhibiting the increase in Pax6 protein in the RPE [6].

Other interactions of FGFR1

  • CONCLUSIONS: FGF2 stimulates Pax6 expression during induction of transdifferentiation of the RPE through FGFR/MEK/Erk signaling cascade [6].
  • After this stage, the level of expression of FGF-R1 increases and its peak of expression at embryonic day 18 is concomitant with the detection of the opsin transcript [15].
  • FGF10 and FGF receptor inhibition cause opposed effects on cell determination and cell proliferation [16].
  • Furthermore, we cloned a novel FGF receptor-like molecule as well as two novel putative RTKs related to the vascular endothelial growth factor (VEGF) receptor [17].
  • Fgf19 expression initiated in the forebrain, and then became restricted to the distal portion of the optic vesicle abutting the future lens placode, where FGF receptor 4 (Fgfr4), a receptor for FGF19, was expressed [18].

Analytical, diagnostic and therapeutic context of FGFR1


  1. Adenovirus-mediated gene transfer of a truncated form of fibroblast growth factor receptor inhibits growth of glioma cells both in vitro and in vivo. Saiki, M., Mima, T., Takahashi, J.C., Tani, S., Yukawa, H., Ueno, H., Mikawa, T., Itoh, N., Kikuchi, H., Hashimoto, N., Miyatake, S. J. Neurooncol. (1999) [Pubmed]
  2. Evaluation of fibroblast growth factor signaling during lens fiber cell differentiation. Huang, J.X., Feldmeier, M., Shui, Y.B., Beebe, D.C. Invest. Ophthalmol. Vis. Sci. (2003) [Pubmed]
  3. Alternating phases of FGF receptor and NGF receptor expression in the developing chicken nervous system. Heuer, J.G., von Bartheld, C.S., Kinoshita, Y., Evers, P.C., Bothwell, M. Neuron (1990) [Pubmed]
  4. Fibroblast growth factor receptor levels decrease during chick embryogenesis. Olwin, B.B., Hauschka, S.D. J. Cell Biol. (1990) [Pubmed]
  5. Differential expression of three chick FGF receptor genes, FGFR1, FGFR2 and FGFR3, in limb and feather development. Noji, S., Koyama, E., Myokai, F., Nohno, T., Ohuchi, H., Nishikawa, K., Taniguchi, S. Prog. Clin. Biol. Res. (1993) [Pubmed]
  6. Retina regeneration in the chick embryo is not induced by spontaneous Mitf downregulation but requires FGF/FGFR/MEK/Erk dependent upregulation of Pax6. Spence, J.R., Madhavan, M., Aycinena, J.C., Del Rio-Tsonis, K. Mol. Vis. (2007) [Pubmed]
  7. FGFR4 signaling is a necessary step in limb muscle differentiation. Marics, I., Padilla, F., Guillemot, J.F., Scaal, M., Marcelle, C. Development (2002) [Pubmed]
  8. Sp1- and Sp3-mediated transcriptional regulation of the fibroblast growth factor receptor 1 gene in chicken skeletal muscle cells. Parakati, R., DiMario, J.X. J. Biol. Chem. (2002) [Pubmed]
  9. Expression of FGFR1, FGFR2 and FGFR3 during early neural development in the chick embryo. Walshe, J., Mason, I. Mech. Dev. (2000) [Pubmed]
  10. Expression patterns of two fibroblast growth factor receptor genes during early chick eye development. Ohuchi, H., Koyama, E., Myokai, F., Nohno, T., Shiraga, F., Matsuo, T., Matsuo, N., Taniguchi, S., Noji, S. Exp. Eye Res. (1994) [Pubmed]
  11. Chordin affects pronephros development in Xenopus embryos by anteriorizing presomitic mesoderm. Mitchell, T., Jones, E.A., Weeks, D.L., Sheets, M.D. Dev. Dyn. (2007) [Pubmed]
  12. Identification of a developmentally regulated protein-tyrosine kinase by using anti-phosphotyrosine antibodies to screen a cDNA expression library. Pasquale, E.B., Singer, S.J. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  13. A new avian fibroblast growth factor receptor in myogenic and chondrogenic cell differentiation. Halevy, O., Monsonego, E., Marcelle, C., Hodik, V., Mett, A., Pines, M. Exp. Cell Res. (1994) [Pubmed]
  14. Locally released retinoic acid leads to facial clefts in the chick embryo but does not alter the expression of receptors for fibroblast growth factor. Richman, J.M., Delgado, J.L. J. Craniofac. Genet. Dev. Biol. (1995) [Pubmed]
  15. Spatial and temporal expression patterns of FGF receptor genes type 1 and type 2 in the developing chick retina. Tcheng, M., Fuhrmann, G., Hartmann, M.P., Courtois, Y., Jeanny, J.C. Exp. Eye Res. (1994) [Pubmed]
  16. FGF signaling is required for determination of otic neuroblasts in the chick embryo. Alsina, B., Abelló, G., Ulloa, E., Henrique, D., Pujades, C., Giraldez, F. Dev. Biol. (2004) [Pubmed]
  17. Molecular cloning of a family of protein kinase genes expressed in the avian embryo. Marcelle, C., Eichmann, A. Oncogene (1992) [Pubmed]
  18. FGF19-FGFR4 signaling elaborates lens induction with the FGF8-L-Maf cascade in the chick embryo. Kurose, H., Okamoto, M., Shimizu, M., Bito, T., Marcelle, C., Noji, S., Ohuchi, H. Dev. Growth Differ. (2005) [Pubmed]
  19. Two distal Sp1-binding cis-elements regulate fibroblast growth factor receptor 1 (FGFR1) gene expression in myoblasts. Patel, S.G., DiMario, J.X. Gene (2001) [Pubmed]
  20. Flg-2, a new member of the family of fibroblast growth factor receptors. Avivi, A., Zimmer, Y., Yayon, A., Yarden, Y., Givol, D. Oncogene (1991) [Pubmed]
  21. The expression of messenger RNAs coding for growth factors, their receptors, and eph-class receptor tyrosine kinases in normal and ototoxically damaged chick cochleae. Pickles, J.O., van Heumen, W.R. Dev. Neurosci. (1997) [Pubmed]
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