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Gene Review

FGF4  -  fibroblast growth factor 4

Gallus gallus

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High impact information on FGF4

  • Remarkably, beads soaked in FGF-1, FGF-2, or FGF-4 and placed in the presumptive flank of chick embryos induce formation of ectopic limb buds, which can develop into complete limbs [1].
  • IGF-I, insulin, FGF-2 and FGF-4 have been implicated in the reciprocal interactions between the apical ectodermal ridge (AER) and underlying mesoderm required for outgrowth and patterning of the developing limb [2].
  • We forced the pigmented epithelium of the embryonic chick eye to express FGF4 [3].
  • Fgf4 positively regulates scleraxis and tenascin expression in chick limb tendons [4].
  • Exogenous implantation of Fgf4 in normal, aneural, and muscleless limbs induces scleraxis and tenascin expression but not that of Fgf8 [4].

Biological context of FGF4


Anatomical context of FGF4

  • The observed movement patterns of anterior streak cells can be explained by an FGF8-mediated chemorepulsion of cells away from the streak followed by chemoattraction toward an FGF4 signal produced by the forming notochord [6].
  • Furthermore, FGF-4 implantation to the hindlimb bud caused additional digit formation accompanying respecification of positional value in the anterior tissue [9].
  • Although FGF-4 implantation to the forelimb bud occasionally induced extra digit 2 formation, no embryos had an extra digit 3 or digit 4, and many specimens exhibited normal skeletal pattern [9].
  • Fibroblast growth factor 4 (Fgf4) has been implicated as a regulator of mesoderm formation, posteriorisation, neural induction and neural patterning [10].
  • FGF-4 signaling is involved in mir-206 expression in developing somites of chicken embryos [11].

Associations of FGF4 with chemical compounds


Other interactions of FGF4

  • Contrary to the model, addition of FGF4 to early limb buds does not activate Hoxa13 prematurely nor extend the Hoxa13 expression domain proximally [5].
  • FGF-2 and FGF-4 can mimic many of the effects of mandibular epithelium from the medial region, including supporting the expression of Msx genes, outgrowth of the mandibular processes and elongation of Meckel's cartilage [13].
  • On the other hand, no ectopic Shh and Hoxd13 expression was detected by grafting an FGF-4 bead into the forelimb bud [9].
  • In contrast, FGF-4 and FGF-10 mRNA expression was significantly increased 2 days after initiation of stretch [14].

Analytical, diagnostic and therapeutic context of FGF4

  • Fgf4, however, was undetectable by RT-PCR in the distal tips of regenerates, suggesting that it does not play the same role in limb regeneration that it does in limb development [15].
  • It was found that Shh expression was locally maintained in the mesenchymal cells underneath and near non-ridge ectoderm in coculture with the posterior mesenchymal cells and non-ridge ectoderm in the presence of FGF-4 by in situ hybridization [16].


  1. Fibroblast growth factors induce additional limb development from the flank of chick embryos. Cohn, M.J., Izpisúa-Belmonte, J.C., Abud, H., Heath, J.K., Tickle, C. Cell (1995) [Pubmed]
  2. IGF-I, insulin and FGFs induce outgrowth of the limb buds of amelic mutant chick embryos. Dealy, C.N., Kosher, R.A. Development (1996) [Pubmed]
  3. FGF-mediated induction of ciliary body tissue in the chick eye. Dias da Silva, M.R., Tiffin, N., Mima, T., Mikawa, T., Hyer, J. Dev. Biol. (2007) [Pubmed]
  4. Fgf4 positively regulates scleraxis and tenascin expression in chick limb tendons. Edom-Vovard, F., Schuler, B., Bonnin, M.A., Teillet, M.A., Duprez, D. Dev. Biol. (2002) [Pubmed]
  5. Characterisation of hoxa gene expression in the chick limb bud in response to FGF. Vargesson, N., Kostakopoulou, K., Drossopoulou, G., Papageorgiou, S., Tickle, C. Dev. Dyn. (2001) [Pubmed]
  6. Cell movement patterns during gastrulation in the chick are controlled by positive and negative chemotaxis mediated by FGF4 and FGF8. Yang, X., Dormann, D., Münsterberg, A.E., Weijer, C.J. Dev. Cell (2002) [Pubmed]
  7. Antagonistic effects of FGF4 on BMP induction of apoptosis and chondrogenesis in the chick limb bud. Buckland, R.A., Collinson, J.M., Graham, E., Davidson, D.R., Hill, R.E. Mech. Dev. (1998) [Pubmed]
  8. Cell migration and chick limb development: chemotactic action of FGF-4 and the AER. Li, S., Muneoka, K. Dev. Biol. (1999) [Pubmed]
  9. Differential response of Shh expression between chick forelimb and hindlimb buds by FGF-4. Wada, N., Nohno, T. Dev. Dyn. (2001) [Pubmed]
  10. Expression of Fgf4 during early development of the chick embryo. Shamim, H., Mason, I. Mech. Dev. (1999) [Pubmed]
  11. FGF-4 signaling is involved in mir-206 expression in developing somites of chicken embryos. Sweetman, D., Rathjen, T., Jefferson, M., Wheeler, G., Smith, T.G., Wheeler, G.N., M??nsterberg, A., Dalmay, T. Dev. Dyn. (2006) [Pubmed]
  12. The ectodermal control in chick limb development: Wnt-7a, Shh, Bmp-2 and Bmp-4 expression and the effect of FGF-4 on gene expression. Akita, K., Francis-West, P., Vargesson, N. Mech. Dev. (1996) [Pubmed]
  13. Region- and stage-specific effects of FGFs and BMPs in chick mandibular morphogenesis. Mina, M., Wang, Y.H., Ivanisevic, A.M., Upholt, W.B., Rodgers, B. Dev. Dyn. (2002) [Pubmed]
  14. Expression of fibroblast growth factor family during postnatal skeletal muscle hypertrophy. Mitchell, P., Steenstrup, T., Hannon, K. J. Appl. Physiol. (1999) [Pubmed]
  15. Fibroblast growth factors in regenerating limbs of Ambystoma: cloning and semi-quantitative RT-PCR expression studies. Christensen, R.N., Weinstein, M., Tassava, R.A. J. Exp. Zool. (2001) [Pubmed]
  16. Synergistic effects of FGF and non-ridge ectoderm on gene expression involved in the formation of the anteroposterior axis of the chick limb bud in cell culture. Kimura, J., Sato-Maeda, M., Noji, S., Ide, H. Dev. Growth Differ. (2000) [Pubmed]
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