Mechanism of somite segmentation by bHLH transcription factors

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Somites, the metameric units of vertebrate embryos, are generated by periodical segmentation, which is regulated by a molecular clock. Hes7, a bHLH gene essential for somite segmentation, displays cyclic expression in the presomitic mesoderm (PSM) with 2 h cycles synchronized with somite formation. Hes7 is also essential for the oscillatory expression of the other gene such as Lunatic fringe (Lfng). It is likely that the cyclic expression of Hes7 is involved in the molecular clock in somite segmentation. Thus, we analyzed the mechanism of the oscillatory expression of Hes7.We show that Hes7 protein is also expressed in a dynamic manner, which depends on proteasome-mediated degradation. Spatial comparison revealed that Hes7 and Lfng transcription occurs in the Hes7 protein-negative domains. Furthermore, Hes7 and Lfng transcription 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 of Hes7 and Lfng, and this negative feedback represents a molecular basis for the segmentation clock.