Cellular and Molecular Life Sciences

, Volume 73, Issue 21, pp 4019–4042 | Cite as

Hes1: the maestro in neurogenesis

  • Sivadasan Bindu Dhanesh
  • Chandramohan Subashini
  • Jackson James
Review

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.

Keywords

Notch signaling Neural stem cell Neural progenitor Gliogenesis Oscillation CNS development 

Abbreviations

Hes

Hairy and enhancer of split

BLBP

Brain lipid-binding protein

NICD

Notch intracellular domain

RBP-Jκ

Recombination signal binding protein for immunoglobulin kappa J region

DAPT

N-[N-(3,5-difluoro-phenacetyl-l-alanyl]-S-phenylglycine tert-butyl ester

FGF

Fibroblast growth factor

JNK

C-Jun N-terminal kinase

ATF2

Activating transcription factor 2

EGF

Epidermal growth factor

MAPK

Mitogen-activated protein kinase

ERK

Extracellular signal-regulated kinases

Shh

Sonic hedgehog

AP1

Activator protein 1

bHLH

Basic helix-loop-helix

Ngn

Neurogenin

ES cells

Embryonic stem cells

BMP

Bone morphogenetic protein

LIF

Leukemia inhibitory factor

Jak

Janus kinase

ROS

Reactive oxygen species

5-HT1A

5-Hydroxytryptamine

Tlx3

T-cell leukemia homeobox protein 3

CDK

Cyclin-dependent kinase

GABA

Gamma-aminobutyric acid

miRNA

microRNA

PDGF

Platelet-derived growth factor

VEGF

Vascular endothelial growth factor

RGC

Retinal ganglion cell

STATs

Signal transducer and activator of transcription

CNTF

Ciliary neurotrophic factor

NGF

Nerve growth factor

TGFβ1

Transforming growth factor beta 1

Amyloid beta

DNMT

DNA methyltransferase

DRG

Dorsal root ganglion

Pax3

Paired box 3

PI3K

Phosphatidylinositol 3 kinase

Lhx2

LIM homeobox 2

VZ

Ventricular zone

SVZ

Subventricular zone

CAT

Chloramphenicol acetyltransferase

TLE

Transducin-like enhancer of split

NFIA

Nuclear factor IA

LNA

Locked nucleic acid

Camk2δ

Ca2+/calmodulin-dependent protein kinase II delta

PARP-1

Poly [ADP-ribose] polymerase 1

PKC

Protein kinase C

DUBs

Deubiquitinating enzymes

PS1

Presenilin

DHA

Docosahexaenoic acid

EPA

Eicosapentaenoic acid

MAP2

Microtubule-associated protein 2

GFAP

Glial fibrillary acidic protein

S100β

S100 calcium-binding protein Β

CGNs

Cerebellar granule neurons

AMPA

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor

AD

Alzheimer’s disease

ZLI

Zona limitans intrathalamica

CNS

Central nervous system

PNS

Peripheral nervous system

NEP

Neuroepithelial progenitors

Id

Inhibitors of differentiation

NPC

Neural progenitor cell

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Copyright information

© Springer International Publishing 2016

Authors and Affiliations

  • Sivadasan Bindu Dhanesh
    • 1
  • Chandramohan Subashini
    • 1
  • Jackson James
    • 1
  1. 1.Neuro Stem Cell Biology Laboratory, Neurobiology DivisionRajiv Gandhi Centre for BiotechnologyThiruvananthapuramIndia

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