Differential display of genes expressed at the midbrain - hindbrain junction identifies sprouty2: an FGF8-inducible member of a family of intracellular FGF antagonists

Mol Cell Neurosci. 2000 Jan;15(1):22-35. doi: 10.1006/mcne.1999.0801.


Specification and polarization of the midbrain and anterior hindbrain involve planar signals originating from the isthmus. Current evidence suggests that FGF8, expressed at the isthmus, provides this patterning influence. In this study, we have sought to identify novel genes which are involved in the process by which regional identity is imparted to midbrain and anterior hindbrain (rhombomere 1). An enhanced differential display reverse transcription method was used to clone cDNAs derived from transcripts expressed specifically in either rhombomere 1 or midbrain during the period of isthmic patterning activity. This gene expression screen identified 28 differentially expressed cDNAs. A clone upregulated in cDNA derived from rhombomere 1 tissue showed a 91% identity at the nucleotide level to the putative human receptor tyrosine kinase antagonist: sprouty2. In situ hybridization on whole chick embryos showed chick sprouty2 to be expressed initially within the isthmus and rhombomere 1, spatially and temporally coincident with Fgf8 expression. However, at later stages this domain was more extensive than that of Fgf8. Introduction of ligand-coated beads into either midbrain or hindbrain region revealed that sprouty2 could be rapidly induced by FGF8. These data suggest that sprouty2 participates in a negative feedback regulatory loop to modulate the patterning activity of FGF8 at the isthmus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Body Patterning
  • Chick Embryo
  • Chickens
  • DNA, Complementary
  • Drosophila
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors / antagonists & inhibitors
  • Fibroblast Growth Factors / genetics*
  • Fibroblast Growth Factors / physiology
  • Gene Expression Regulation, Developmental*
  • Humans
  • Mesencephalon / embryology*
  • Mice
  • Molecular Sequence Data
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics*
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Rhombencephalon / embryology*
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Transcription, Genetic


  • DNA, Complementary
  • FGF8 protein, human
  • Fgf8 protein, mouse
  • Nerve Tissue Proteins
  • Spry2 protein, rat
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors
  • Receptor Protein-Tyrosine Kinases