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


RESULTS
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.
Laboratory of Gene Regulation Research, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Japan.
Shinichi
S
Hayashi
Taiju
T
Shimoda
Masato
M
Nakajima
Yuki
Y
Tsukada
Yuichi
Y
Sakumura
J Kim
JK
Dale
Miguel
M
Maroto
Kenji
K
Kohno
Takaaki
T
Matsui
Yasumasa
Y
Bessho
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000502:physiology; D001683:Biological Clocks / Q000502:physiology*; D015153:Blotting, Western; D004622:Embryo, Mammalian / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors*; D018507:Gene Expression Regulation, Developmental; D016695:Glycosyltransferases / Q000378:metabolism; D017403:In Situ Hybridization; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics*; D051880:Receptors, Notch / Q000378:metabolism*; D015027:Zebrafish / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D005346:Fibroblast Growth Factors; D016695:Glycosyltransferases; D009419:Nerve Tissue Proteins; D051880:Receptors, Notch; C430525:Hes7 protein, mouse; C499037:Spry4 protein, mouse; C498392:Lfng protein, mouse