The Hes gene family: repressors and oscillators that orchestrate embryogenesis

Abstract

Embryogenesis involves orchestrated processes of cell proliferation and differentiation. The mammalian Hes basic helix-loop-helix repressor genes play central roles in these processes by maintaining progenitor cells in an undifferentiated state and by regulating binary cell fate decisions. Hes genes also display an oscillatory expression pattern and control the timing of biological events, such as somite segmentation. Many aspects of Hes expression are regulated by Notch signaling, which mediates cell-cell communication. This primer describes these pleiotropic roles of Hes genes in some developmental processes and aims to clarify the basic mechanism of how gene networks operate in vertebrate embryogenesis.

Hes1: a key role in stemness, metastasis and multidrug resistance

“…[6][7][8][9][10][11] Hes1 factors is identified with 3 conserved domains: the bHLH, Orange and WRPW domains. The bHLH domain of Hes1 is responsible for interaction with lineage-specific bHLH factors; for instance, it can form a functional heterodimer with other bHLH factors, such as E47, Id proteins as well as its homologies hey1/2.…”

“…12,[13][14][15] Within the bHLH region, Hes1 has a proline residue which exhibits unique binding ability to N box (CACNAG), differing from other bHLH factors which have higher affinity to E box (CANNTG). 11 The orange domain is less conserved and confers selection specificity of bHLH heterodimer partner. 11,16 Another functional region, the WRPW domain, is characterized with the C-terminal Trp-Arg-Pro-Trp sequence.…”

Cath6, a bHLH atonal family proneural gene, negatively regulates neuronal differentiation in the retina

“…Some bHLH genes, such as the Hes or Id families, are reported to antagonize proneural bHLH proteins by forming nonfunctional heterodimers with their partner proteins called E proteins through their HLH domains (reviewed in Kageyama et al, 2005Kageyama et al, , 2007. Our finding excludes a possibility that Cath6 acts through this sequestering mechanism and suggests that Cath6 functions by a different molecular mechanism from the Hes or Id families.…”

“…These proneural bHLH genes are proposed to be negatively regulated by another class of bHLH genes, Hes genes (Ishibashi et al, 1995;Lee et al, 2005). Hes genes down-regulate proneural gene expression or antagonize its function through protein-protein interactions, resulting in the maintenance of the undifferentiated state of progenitor cells (reviewed in Kageyama et al, 2007). In the chicken CMZ, the expression of the Hes family gene, Hairy1, is under the control of Wnt signaling, which is necessary and sufficient for the maintenance of stem celllike characteristics of the marginal retina, thereby maintaining the undifferentiated state of the CMZ (Kubo and Nakagawa, 2009).…”

Correlation of Notch1/Hes1 Genes Expression Levels in Egyptian Paediatric Patients with Newly Diagnosed and Persistent Primary Immune(Idiopathic) Thrombocytopenic Purpura

“…Meanwhile, Hes1 regulates the fate of various cell lineages in developing organs, including T-cells [25].…”