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

• Consequently, the differential, spatial regulation of Hes1 and Hes5 gene expression by the Notch signaling pathway in developing nephrons may be a mechanism for patterning cell fate decisions during nephron morphogenesis [4].
• Expression of Hairy/Enhancer of Split genes, Hes1 and Hes5, during murine nephron morphogenesis [4].
• These findings were accompanied by up-regulation of Mash1 and down-regulation of Hes5 proteins [5].
• Neither Hes1 (hairy and enhancer of split) nor Hes5 appeared to mediate gp130-enhanced NOTCH1 signaling that regulates NSC maintenance [6].
• Conversely, Hes5-deficient retina showed 30-40% decrease of Müller glial cell number without affecting cell survival [1].

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

• In contrast, expression of Hes5 is restricted to clusters of neural progenitor cells and requires Mash1 function [11].
• Hes5 synergizes with Hes1 and regulates neurogenesis at the level of Ngn1 expression [11].
• We also showed that down-regulation of Hes5 and up-regulation of Math1 were associated with ectopic hair cell induction [12].
• In the VNO, Hes6 was expressed throughout the sensory epithelium (S-VNO) at embryonic day 12, and later became restricted to a single layer of cells in the basal region of the S-VNO, where Hes5-expressing undifferentiated cells were present [13].
• These results suggest that the Hes-3 and Hes-5 genes may be clustered on chromosome 4 while the Hes-1 gene is not [14].

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].

References