Periodic repression by the bHLH factor Hes7 is an essential mechanism for the somite segmentation clock

Abstract

Hes7, a bHLH gene essential for somitogenesis, displays cyclic expression of mRNA in the presomitic mesoderm (PSM). Here, we show that Hes7 protein is also expressed in a dynamic manner, which depends on proteasome-mediated degradation. Spatial comparison revealed thatHes7andLunatic fringe(Lfng) transcription occurs in the Hes7 protein-negative domains. Furthermore,Hes7andLfngtranscription is constitutively up-regulated in the absence of Hes7 protein and down-regulated by stabilization of Hes7 protein. Thus, periodic repression by Hes7 protein is critical for the cyclic transcription ofHes7andLfng, and this negative feedback represents a molecular basis for the segmentation clock.