sprouty4 acts in vivo as a feedback-induced antagonist of FGF signaling in zebrafish

Fürthauer, M., Reifers, F., Brand, M., Thisse, B., and Thisse, C.
Development (Cambridge, England)   128(12): 2175-2186 (Journal)
Registered Authors
Brand, Michael, Fürthauer, Maximilian, Reifers, Frank, Thisse, Bernard, Thisse, Christine
BMP; sprouty4; FGF3; FGF8; FGFR; ERK; MAPK; Ras; morpholino; zebrafish
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cerebellum/abnormalities
  • Cerebellum/embryology
  • Cerebellum/metabolism
  • DNA, Complementary
  • Fibroblast Growth Factor 3
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors/antagonists & inhibitors*
  • Fibroblast Growth Factors/genetics
  • Fibroblast Growth Factors/metabolism
  • Fibroblast Growth Factors/physiology
  • Gene Expression Profiling
  • Molecular Sequence Data
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/metabolism*
  • Nerve Tissue Proteins/physiology
  • Phenotype
  • Proto-Oncogene Proteins/genetics
  • Proto-Oncogene Proteins/metabolism
  • Proto-Oncogene Proteins/physiology
  • Receptor Protein-Tyrosine Kinases/metabolism
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptors, Fibroblast Growth Factor/metabolism
  • Signal Transduction*
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins*
11493538 Full text @ Development
In looking for novel factors involved in the regulation of the fibroblast growth factor (FGF) signaling pathway, we have isolated a zebrafish sprouty4 gene, based on its extensive similarities with the expression patterns of both fgf8 and fgf3. Through gain- and loss-of-function experiments, we demonstrate that Fgf8 and Fgf3 act in vivo to induce the expression of Spry4, which in turn can inhibit activity of these growth factors. When overexpressed at low doses, Spry4 induces loss of cerebellum and reduction in size of the otic vesicle, thereby mimicking the fgf8/acerebellar mutant phenotype. Injections of high doses of Spry4 cause ventralization of the embryo, an opposite phenotype to the dorsalisation induced by overexpression of Fgf8 or Fgf3. Conversely we have shown that inhibition of Spry4 function through injection of antisense morpholino oligonucleotide leads to a weak dorsalization of the embryo, the phenotype expected for an upregulation of Fgf8 or Fgf3 signaling pathway. Finally, we show that Spry4 interferes with FGF signaling downstream of the FGF receptor 1 (FGFR1). In addition, our analysis reveals that signaling through FGFR1/Ras/mitogen-activated protein kinase pathway is involved, not in mesoderm induction, but in the control of the dorsoventral patterning via the regulation of bone morphogenetic protein (BMP) expression.
Genes / Markers
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Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes