Instability of Hes7 protein is crucial for the somite segmentation clock

Nat Genet. 2004 Jul;36(7):750-4. doi: 10.1038/ng1372. Epub 2004 May 30.


During somitogenesis, a pair of somites buds off from the presomitic mesoderm every 2 hours in mouse embryos, suggesting that somite segmentation is controlled by a biological clock with a 2-hour cycle. Expression of the basic helix-loop-helix factor Hes7, an effector of Notch signaling, follows a 2-hour oscillatory cycle controlled by negative feedback; this is proposed to be the molecular basis for the somite segmentation clock. If the proposal is correct, this clock should depend crucially on the short lifetime of Hes7. To address the biological importance of Hes7 instability, we generated mice expressing mutant Hes7 with a longer half-life (approximately 30 min compared with approximately 22 min for wild-type Hes7) but normal repressor activity. In these mice, somite segmentation and oscillatory expression became severely disorganized after a few normal cycles of segmentation. We simulated this effect mathematically using a direct autorepression model. Thus, instability of Hes7 is essential for sustained oscillation and for its function as a segmentation clock.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Line
  • Mice
  • Mice, Inbred C3H
  • Somites*
  • Transcription Factors / genetics
  • Transcription Factors / physiology*


  • Basic Helix-Loop-Helix Transcription Factors
  • Hes7 protein, mouse
  • Transcription Factors