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Gene Review

HES4  -  hairy and enhancer of split 4 (Drosophila)

Gallus gallus

Synonyms: HAIRY1, HES1, c-hairy1A
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Disease relevance of HES1


High impact information on HES1

  • Vertebrate somitogenesis is associated with a molecular oscillator, the segmentation clock, which is defined by the periodic expression of genes related to the Notch pathway such as hairy1 and hairy2 or lunatic fringe (referred to as the cyclic genes) in the presomitic mesoderm (PSM) [2].
  • Thus, Notch1 signaling induces apoptosis of the B cells through Hairy1, and the G(1) cell cycle arrest through other pathways [3].
  • A role for hairy1 in regulating chick limb bud growth [4].
  • Viral misexpression of c-hairy1A causes a reduction in size of the limb and shortened skeletal elements, without affecting the chondrocyte differentiation program [4].

Biological context of HES1

  • Based on previous and current findings, we propose that HES1 serves as a convergent signaling node within early retinal progenitor cells to integrate various cell-extrinsic cues, including VEGF and SHH, in order to control cell proliferation and neuronal specification [1].
  • Members of the Hairy/Enhancer of Split family of DNA binding transcriptional repressors can be effectors of Notch signaling and often act to maintain cell populations in an undifferentiated, proliferating state, properties predicted for the distal limb mesenchyme [4].

Anatomical context of HES1

  • We conclude that c-hairy1 regulates the size of the limb, suggesting a role for Notch signaling in the distal mesenchyme [4].


  1. VEGF activates divergent intracellular signaling components to regulate retinal progenitor cell proliferation and neuronal differentiation. Hashimoto, T., Zhang, X.M., Chen, B.Y., Yang, X.J. Development (2006) [Pubmed]
  2. Onset of the segmentation clock in the chick embryo: evidence for oscillations in the somite precursors in the primitive streak. Jouve, C., Iimura, T., Pourquie, O. Development (2002) [Pubmed]
  3. Cell cycle arrest and apoptosis induced by Notch1 in B cells. Morimura, T., Goitsuka, R., Zhang, Y., Saito, I., Reth, M., Kitamura, D. J. Biol. Chem. (2000) [Pubmed]
  4. A role for hairy1 in regulating chick limb bud growth. Vasiliauskas, D., Laufer, E., Stern, C.D. Dev. Biol. (2003) [Pubmed]
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