Control of Hes7 expression by Tbx6, the Wnt pathway and the chemical Gsk3 inhibitor LiCl in the mouse segmentation clock

PLoS One. 2013;8(1):e53323. doi: 10.1371/journal.pone.0053323. Epub 2013 Jan 9.


The mouse segmentation is established from somites, which are iteratively induced every two hours from the presomitic mesoderm (PSM) by a system known as the segmentation clock. A crucial component of the segmentation clock is the gene Hes7, which is regulated by the Notch and Fgf/Mapk pathways, but its relation to other pathways is unknown. In addition, chemical alteration of the Wnt pathway changes the segmentation clock period but the mechanism is unclear.To clarify these questions, we have carried out Hes7 promoter analysis in transgenic mouse embryos and have identified an essential 400 bp region, which contains binding sites of Tbx6 and the Wnt signaling effector Lef1. We have found that the Hes7 promoter is activated by Tbx6, and normal activity of the Hes7 promoter in the mouse PSM requires Tbx6 binding sites. Our results demonstrate that Wnt pathway molecules activate the Hes7 promoter cooperatively with Tbx6 in cell culture and are necessary for its proper expression in the mouse PSM. Furthermore, it is shown that the chemical Gsk3 inhibitor LiCl lengthens the oscillatory period of Hes7 promoter activity.Our data suggest that Tbx6 and the Wnt pathway cooperatively regulate proper Hes7 expression. Furthermore, proper Hes7 promoter activity and expression is important for the normal pace of oscillation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Pairing / genetics
  • Base Sequence
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Binding Sites / genetics
  • Biological Clocks / genetics*
  • Body Patterning / drug effects
  • Body Patterning / genetics*
  • Embryo, Mammalian / metabolism
  • Gene Expression Regulation, Developmental / drug effects
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors*
  • Glycogen Synthase Kinase 3 / metabolism
  • Lithium Chloride / pharmacology*
  • Mice
  • Mice, Transgenic
  • Models, Biological
  • Molecular Sequence Data
  • Promoter Regions, Genetic / genetics
  • Protein Binding / drug effects
  • Protein Binding / genetics
  • Protein Kinase Inhibitors / pharmacology
  • Transcription Factors / metabolism*
  • Wnt Signaling Pathway / drug effects
  • Wnt Signaling Pathway / genetics*


  • Basic Helix-Loop-Helix Transcription Factors
  • Hes7 protein, mouse
  • Protein Kinase Inhibitors
  • Tbx6 protein, mouse
  • Transcription Factors
  • Glycogen Synthase Kinase 3
  • Lithium Chloride

Grant support

This work was supported by Grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan. AG was partly supported by postdoctoral grant P06237 awarded by the Japan Society for the Promotion of Science. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.