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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.

Control of Hes7 Expression by Tbx6, the Wnt Pathway and the Chemical Gsk3 Inhibitor LiCl in the Mouse Segmentation Clock