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Gene Review

Hes5  -  hairy and enhancer of split 5 (Drosophila)

Mus musculus

Synonyms: Hairy and enhancer of split 5, Hes-5, Transcription factor HES-5, bHLHb38
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Disease relevance of Hes5

  • Here, we found that, in mouse retina, the bHLH gene Hes5 was specifically expressed by differentiating Müller glial cells and that misexpression of Hes5 with recombinant retrovirus significantly increased the population of glial cells at the expense of neurons [1].

High impact information on Hes5

  • We report here upregulation of myelin gene expression in Hes5-/- mice compared to wild-type siblings and downregulation in overexpressing progenitors [2].
  • A molecular insight of Hes5-dependent inhibition of myelin gene expression: old partners and new players [2].
  • Novel mechanisms of Hes5 function in the oligodendrocyte lineage include the regulation of feedback loops with the cell-specific transcriptional activator Sox10 [2].
  • In progenitors with low levels of Sox10, Hes5 further decreases the bioavailability of this protein by transcriptional inhibition and direct sequestration of this activator [2].
  • Hes1 and Hes5 as notch effectors in mammalian neuronal differentiation [3].

Biological context of Hes5


Anatomical context of Hes5

  • Hes-transplanted mice remained healthy but cells transduced with Hes1 or Hes5 were partially impaired in their ability to differentiate into B cells [7].
  • Hes1-, Hes5- and Notch1IC-transduced bone marrow cells cultured ex vivo in a colony forming assay in the presence of cytokines that promote myeloid differentiation remained very immature, indicating that the myeloid potential of these bone marrow cells was altered [7].
  • We found that Hes5 is specifically expressed in the anlage of the loop of Henle, suggesting that it might be involved in the determination of its cell identity [8].
  • Hes5 coincides with the majority of Notch1 expression and can be detected in the cerebral cortex, cerebellum and putative germinal zones [9].
  • We demonstrated that Hes1 and Hes5, two members of the inhibitory bHLH transcription factors, act as negative regulators of hair cell differentiation [10].

Associations of Hes5 with chemical compounds

  • These data show that Hes1 and Hes5 expression are independently regulated along the proximal-distal axis of the developing nephron [4].

Regulatory relationships of Hes5

  • Hes1 and Hes5 are expressed with distinct patterns in the olfactory placodes and are subject to different regulatory mechanisms [11].

Other interactions of Hes5


Analytical, diagnostic and therapeutic context of Hes5

  • The disruption of Notch signaling by a gamma-secretase inhibitor in an in vitro organ culture system of wild-type cochleae resulted in a reduction in expression of the Notch target gene Hes5 and an increase in hair cell differentiation [15].


  1. Glial cell fate specification modulated by the bHLH gene Hes5 in mouse retina. Hojo, M., Ohtsuka, T., Hashimoto, N., Gradwohl, G., Guillemot, F., Kageyama, R. Development (2000) [Pubmed]
  2. A molecular insight of Hes5-dependent inhibition of myelin gene expression: old partners and new players. Liu, A., Li, J., Marin-Husstege, M., Kageyama, R., Fan, Y., Gelinas, C., Casaccia-Bonnefil, P. EMBO J. (2006) [Pubmed]
  3. Hes1 and Hes5 as notch effectors in mammalian neuronal differentiation. Ohtsuka, T., Ishibashi, M., Gradwohl, G., Nakanishi, S., Guillemot, F., Kageyama, R. EMBO J. (1999) [Pubmed]
  4. Expression of Hairy/Enhancer of Split genes, Hes1 and Hes5, during murine nephron morphogenesis. Piscione, T.D., Wu, M.Y., Quaggin, S.E. Gene Expr. Patterns (2004) [Pubmed]
  5. Central nervous system myelination in mice with deficient expression of Notch1 receptor. Givogri, M.I., Costa, R.M., Schonmann, V., Silva, A.J., Campagnoni, A.T., Bongarzone, E.R. J. Neurosci. Res. (2002) [Pubmed]
  6. Glycoprotein 130 signaling regulates Notch1 expression and activation in the self-renewal of mammalian forebrain neural stem cells. Chojnacki, A., Shimazaki, T., Gregg, C., Weinmaster, G., Weiss, S. J. Neurosci. (2003) [Pubmed]
  7. Overexpression of the Notch target genes Hes in vivo induces lymphoid and myeloid alterations. Kawamata, S., Du, C., Li, K., Lavau, C. Oncogene (2002) [Pubmed]
  8. Segmental expression of Notch and Hairy genes in nephrogenesis. Chen, L., Al-Awqati, Q. Am. J. Physiol. Renal Physiol. (2005) [Pubmed]
  9. Notch1 and its ligands Delta-like and Jagged are expressed and active in distinct cell populations in the postnatal mouse brain. Stump, G., Durrer, A., Klein, A.L., Lütolf, S., Suter, U., Taylor, V. Mech. Dev. (2002) [Pubmed]
  10. Notch/Notch ligands and Math1 expression patterns in the organ of Corti of wild-type and Hes1 and Hes5 mutant mice. Zine, A., de Ribaupierre, F. Hear. Res. (2002) [Pubmed]
  11. Hes genes regulate sequential stages of neurogenesis in the olfactory epithelium. Cau, E., Gradwohl, G., Casarosa, S., Kageyama, R., Guillemot, F. Development (2000) [Pubmed]
  12. Inhibition of Notch/RBP-J signaling induces hair cell formation in neonate mouse cochleas. Yamamoto, N., Tanigaki, K., Tsuji, M., Yabe, D., Ito, J., Honjo, T. J. Mol. Med. (2006) [Pubmed]
  13. Expression of Hes6 and NeuroD in the olfactory epithelium, vomeronasal organ and non-sensory patches. Suzuki, Y., Mizoguchi, I., Nishiyama, H., Takeda, M., Obara, N. Chem. Senses (2003) [Pubmed]
  14. Structure and chromosomal locus of the mouse gene encoding a cerebellar Purkinje cell-specific helix-loop-helix factor Hes-3. Sakagami, T., Sakurada, K., Sakai, Y., Watanabe, T., Nakanishi, S., Kageyama, R. Biochem. Biophys. Res. Commun. (1994) [Pubmed]
  15. COUP-TFI controls Notch regulation of hair cell and support cell differentiation. Tang, L.S., Alger, H.M., Pereira, F.A. Development (2006) [Pubmed]
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