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Vertebrate Sprouty genes are induced by FGF signaling and can cause chondrodysplasia when overexpressed.

The Drosophila sprouty gene encodes an antagonist of FGF and EGF signaling whose expression is induced by the signaling pathways that it inhibits. Here we describe a family of vertebrate Sprouty homologs and demonstrate that the regulatory relationship with FGF pathways has been conserved. In both mouse and chick embryos, Sprouty genes are expressed in intimate association with FGF signaling centers. Gain- and loss-of-function experiments demonstrate that FGF signaling induces Sprouty gene expression in various tissues. Sprouty overexpression obtained by infecting the prospective wing territory of the chick embryo with a retrovirus containing a mouse Sprouty gene causes a reduction in limb bud outgrowth and other effects consistent with reduced FGF signaling from the apical ectodermal ridge. At later stages of development in the infected limbs there was a dramatic reduction in skeletal element length due to an inhibition of chondrocyte differentiation. The results provide evidence that vertebrate Sprouty proteins function as FGF-induced feedback inhibitors, and suggest a possible role for Sprouty genes in the pathogenesis of specific human chondrodysplasias caused by activating mutations in Fgfr3.

Pubmed ID: 10498682


  • Minowada G
  • Jarvis LA
  • Chi CL
  • Neub├╝ser A
  • Sun X
  • Hacohen N
  • Krasnow MA
  • Martin GR


Development (Cambridge, England)

Publication Data

October 19, 1999

Associated Grants

  • Agency: NCI NIH HHS, Id: CA78711
  • Agency: NCI NIH HHS, Id: K08CA09302

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Chick Embryo
  • Cloning, Molecular
  • Drosophila
  • Drosophila Proteins
  • Evolution, Molecular
  • Extremities
  • Female
  • Fibroblast Growth Factors
  • Gene Expression Regulation, Developmental
  • Humans
  • Insect Proteins
  • Male
  • Membrane Proteins
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Mutation
  • Osteochondrodysplasias
  • Pregnancy
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Species Specificity