Hes1: the maestro in neurogenesis

Abstract

The process of neurogenesis is well orchestrated by the harmony of multiple cues in a spatiotemporal manner. In this review, we focus on how a dynamic gene, Hes1, is involved in neurogenesis with the view of its regulation and functional implications. Initially, we have reviewed the immense functional significance drawn by this maestro during neural development in a context-dependent manner. How this indispensable role of Hes1 in conferring the competency for neural differentiation partly relies on the direct/indirect mode of repression mediated by very specific structural and functional arms of this protein has also been outlined here. We also review the detailed molecular mechanisms behind the well-tuned oscillatory versus sustained expression of this antineurogenic bHLH repressor, which indeed makes it a master gene to implement the elusive task of neural progenitor propensity. Apart from the functional aspects of Hes1, we also discuss the molecular insights into the endogenous regulatory machinery that regulates its expression. Though Hes1 is a classical target of the Notch signaling pathway, we discuss here its differential expression at the molecular, cellular, and/or regional level. Moreover, we describe how its expression is fine-tuned by all possible ways of gene regulation such as epigenetic, transcriptional, post-transcriptional, post-translational, and environmental factors during vertebrate neurogenesis.

Costunolide represses hepatic fibrosis through WW domain‐containing protein 2‐mediated Notch3 degradation

“…Lysosomal degradation has recently been shown to account for NICD3 clearance and the attenuation of NICD3 target gene activation (Jia et al, ). As an important component of the Notch signaling pathway, HES1, which belongs to the highly conserved basic helix‐loop‐helix family of transcription factors and exerts its biological function by binding to N‐boxes (CACNAG), is required for cell proliferation (Rani, Greenlaw, Smith, & Galustian, ), differentiation (Dhanesh, Subashini, & James, ) and liver fibrogenesis (Zhang, Zhang et al, ). In the present study, COS down‐regulated the Notch3–HES1 pathway and the decrease in HES1 expression correlated with the increase in NICD3 monoubiquitination levels and lysosomal degradation.…”

MicroRNA‑381/Hes1 is a potential therapeutic target for spinal cord injury

“…The Hes family basic helix-loop-helix (bHLH) transcription factor 1 (Hes1) gene exists in the majority of mammals, expressed to a large extent in the epithelial and neuroepithelial cells during the embryonic development process (11). As a bHLH DNA-binding protein, neurogenic locus notch homolog protein 1 (Hesl protein) can block the activation pathway through binding with target DNA or other HLH proteins (including achaete-scute homolog 1 and E47) directly, thus inhibiting transcription and finally inhibiting cell differentiation (12).…”

Human cytomegalovirus IE1 downregulates Hes1 in neural progenitor cells as a potential E3 ubiquitin ligase

“…This regulatory role is achieved, at least partially, through essential downstream effectors such as the Hairy and Enhancer of Split (Hes) proteins, which belong to the repressor-type basic helix-loop-helix family [ 14 , 15 ]. Hes1 is one of seven members in the Hes family, which play a crucial role in maintaining the undifferentiated and proliferative status of NPCs [ 16 – 18 ]. The auto-negative feedback regulation at the transcription level, the instability of the mRNA, and the rapid ubiquitination-dependent proteasomal degradation of the protein together result in the well-regulated Hes1 oscillation, which in turn fine-tunes the timing of NPC proliferation and differentiation and further controls the shape, size and integrity of brain structures [ 13 , 19 – 21 ].…”