Abstract
The process of neurogenesis, through which the entire nervous system of an organism is formed, has attracted immense scientific attention for decades. How can a single neural stem cell give rise to astrocytes, oligodendrocytes, and neurons? Furthermore, how is a neuron led to choose between the hundreds of different neuronal subtypes that the vertebrate CNS contains? Traditionally, niche signals and transcription factors have been on the spotlight. Recent research is increasingly demonstrating that the answer may partially lie in epigenetic regulation of gene expression. In this article, we comprehensively review the role of post-translational histone modifications in neurogenesis in both the embryonic and adult CNS.
Highlights
Histone post-translational modifications (PTMs) have been implicated in a multitude of developmental processes and diseases (Bhaumik et al, 2007; Chi et al, 2010; Tyssowski et al, 2014; Yao and Jin, 2014)
The authors showed that knockdown of JMJD2A/KDM4A and JMJD2C/KDM4C by siRNA in embryonic cortical neural stem and progenitor cells (NSPCs) led to precocious astrogliogenesis and decreased neurogenesis associated with increased cell death
Initiation of Chromatin Modifications in the Context of Neurogenesis. What is it that triggers the initiation of chromatin modifications associated with neurogenesis? It appears that known signals that induce neurogenesis under certain contexts, such as fibroblast growth factors (FGFs) (Kengaku and Okamoto, 1993), neurotrophins (Bartkowska et al, 2007), bone morphogenic proteins (BMPs) (Andersson et al, 2011; Bond et al, 2012) and other members of the transforming growth factor β (TGFβ) (Rodriguez-Martínez and Velasco, 2012) family trigger the initiation of histone PTMs
Summary
Histone post-translational modifications (PTMs) have been implicated in a multitude of developmental processes and diseases (Bhaumik et al, 2007; Chi et al, 2010; Tyssowski et al, 2014; Yao and Jin, 2014). The goal of this review is to provide an overview of the current evidence for histone PTM involvement in neurogenesis, the known mechanisms that initiate these processes, as well as investigate the contribution of histone PTMs to the complex and interconnected network of epigenetic modifications. Neurogenesis in vertebrates begins after ectodermal cells acquire a neuroepithelial identity through the process of induction and subsequent morphological transformation to become radial “glial” cells with stem cell properties (Dang and Tropepe, 2006; Kriegstein and Alvarez-Buylla, 2009). Isolated neural stem cells from the embryonic cerebral cortex follow the same order of differentiation in vitro, initially giving rise to neurons and astrocytes (Qian et al, 2000).
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