PUBLICATION

The roles of the FGF signal in zebrafish embryos analyzed using constitutive activation and dominant-negative suppression of different FGF receptors

Authors
Ota, S., Tonou-Fujimori, N., and Yamasu, K.
ID
ZDB-PUB-081121-21
Date
2009
Source
Mechanisms of Development   126(1-2): 1-17 (Journal)
Registered Authors
Ota, Satoshi, Yamasu, Kyo
Keywords
none
MeSH Terms
  • Signal Transduction*
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Gene Expression Regulation, Developmental
  • Body Patterning
  • Embryo, Nonmammalian/embryology*
  • Embryo, Nonmammalian/metabolism*
  • Solubility
  • Animals
  • Receptors, Fibroblast Growth Factor/deficiency
  • Receptors, Fibroblast Growth Factor/genetics
  • Receptors, Fibroblast Growth Factor/metabolism*
  • Fibroblast Growth Factors/metabolism*
  • Ligands
  • RNA, Messenger/genetics
(all 16)
PubMed
19015027 Full text @ Mech. Dev.
Abstract
The roles of the FGF family growth factors and their receptors (FGFRs) in zebrafish embryos were examined using variously modified versions of the four FGFR genes (fgfr1-4). Constitutively active forms of all of the examined FGFRs (ca-FGFRs) caused dorsalization, brain caudalization, and secondary axis formation, indicating that the main FGF signal transduction downstream of the receptor is highly similar among FGFRs. All of the membrane-bound type of dominant-negative FGFRs (mdn-FGFRs) derived from the four fgfr genes, which interfere with endogenous FGFRs, produced posterior truncation, as previously reported in both Xenopus and zebrafish. mdn-FGFR3c had the strongest effects on embryos, progressively disrupting the posterior structure as the dose increased. At the highest dose, only the forebrain was formed. At lower doses, mdn-FGFR3c mainly suppressed the paraxial mesoderm. The co-injection of mRNA for different mdn-FGFRs and FGFs resulted in diverse suppression spectra of the respective FGFRs against FGFs. Only mdn-FGFR3c severely suppressed all of the FGFs examined. We also examined the effects of the secretory type of dominant-negative FGFRs (sdn-FGFRs), which are released from cells and trap FGF ligands. Only sdn-FGFR3c resulted in the characteristic effect of selectively disrupting the isthmic development, as well as the tailbud. The co-injection of the mRNA for sdn-FGFRs and FGFs suggested that sdn-FGFR3c inhibits FGFs of the FGF8 subfamily, which is consistent with its specific effects on development. We discuss the implications of our findings obtained in the present study.
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Citation
Ota, S., Tonou-Fujimori, N., and Yamasu, K. (2009) The roles of the FGF signal in zebrafish embryos analyzed using constitutive activation and dominant-negative suppression of different FGF receptors. Mechanisms of Development. 126(1-2):1-17.