Sprouty4, an FGF inhibitor, displays cyclic gene expression under the control of the notch segmentation clock in the mouse PSM

PLoS One. 2009;4(5):e5603. doi: 10.1371/journal.pone.0005603. Epub 2009 May 19.

Abstract

Background: During vertebrate embryogenesis, somites are generated at regular intervals, the temporal and spatial periodicity of which is governed by a gradient of fibroblast growth factor (FGF) and/or Wnt signaling activity in the presomitic mesoderm (PSM) in conjunction with oscillations of gene expression of components of the Notch, Wnt and FGF signaling pathways.

Principal findings: Here, we show that the expression of Sprouty4, which encodes an FGF inhibitor, oscillates in 2-h cycles in the mouse PSM in synchrony with other oscillating genes from the Notch signaling pathway, such as lunatic fringe. Sprouty4 does not oscillate in Hes7-null mutant mouse embryos, and Hes7 can inhibit FGF-induced transcriptional activity of the Sprouty4 promoter.

Conclusions: Thus, periodic expression of Sprouty4 is controlled by the Notch segmentation clock and may work as a mediator that links the temporal periodicity of clock gene oscillations with the spatial periodicity of boundary formation which is regulated by the gradient of FGF/Wnt activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / physiology
  • Biological Clocks / physiology*
  • Blotting, Western
  • Embryo, Mammalian / metabolism
  • Fibroblast Growth Factors / antagonists & inhibitors*
  • Gene Expression Regulation, Developmental*
  • Glycosyltransferases / metabolism
  • In Situ Hybridization
  • Mesoderm / embryology
  • Mesoderm / metabolism*
  • Mice
  • Mice, Transgenic
  • Nerve Tissue Proteins / genetics*
  • Receptors, Notch / metabolism*
  • Zebrafish / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Hes7 protein, mouse
  • Nerve Tissue Proteins
  • Receptors, Notch
  • Spry4 protein, mouse
  • Fibroblast Growth Factors
  • Glycosyltransferases
  • Lfng protein, mouse