Abstract
Neurogenesis is the process through which neural stem and progenitor cells generate neurons. During the development of the mouse neocortex, stem and progenitor cells sequentially give rise to neurons destined to different cortical layers and then switch to gliogenesis resulting in the generation of astrocytes and oligodendrocytes. Precise spatial and temporal regulation of neural progenitor differentiation is key for the proper formation of the complex structure of the neocortex. Dynamic changes in gene expression underlie the coordinated differentiation program, which enables the cells to generate the RNAs and proteins required at different stages of neurogenesis and across different cell types. Here, we review the contribution of epigenetic mechanisms, with a focus on Polycomb proteins, to the regulation of gene expression programs during mouse neocortical development. Moreover, we discuss the recent emerging concept of epigenetic and transcriptional pre-patterning in neocortical progenitor cells as well as post-transcriptional mechanisms for the fine-tuning of mRNA abundance.
Highlights
The generation of neocortical neurons during mouse development is the result of balanced proliferative and differentiative divisions of neural stem and progenitor cells (Götz and Huttner, 2005; Lui et al, 2011; Florio and Huttner, 2014)
We will mainly focus on post-translational modifications of histones, as the role of other epigenetic pathways, including DNA modifications and chromatin remodeling, in neocortex development are reviewed elsewhere
By mediating the timed termination of Fezf2 expression, Ring1b regulates the number of subcerebral projection neurons produced. These data suggest that PcG complexes and associated proteins control several aspects of cortical neurogenesis, including the balance between self-renewal and differentiation of apical radial glia (aRG) as well as the switch from deep- to upper-layer neurogenesis in neural progenitor cells (NPCs)
Summary
The generation of neocortical neurons during mouse development is the result of balanced proliferative and differentiative divisions of neural stem and progenitor cells (Götz and Huttner, 2005; Lui et al, 2011; Florio and Huttner, 2014). With the onset of neurogenesis at around mouse embryonic day (E) 10, NECs transform into apical radial glia (aRG), which retain apico-basal polarity and become more elongated. Their cell bodies reside in the ventricular zone, whereas their long basal processes extend to the basal lamina and provide a scaffold for neuronal migration to the cortical plate. BIPs delaminate from the ventricular surface and reside in the subventricular zone They lack apico-basal polarity and in mouse typically divide symmetrically to produce two neurons. Throughout mouse neocortical development, the potential of neural progenitor cells (NPCs) for proliferation and differentiation changes as NPCs pass through phases of expansion, deep- and upper-layer neurogenesis, and gliogenesis. We will mainly focus on post-translational modifications of histones, as the role of other epigenetic pathways, including DNA modifications and chromatin remodeling, in neocortex development are reviewed elsewhere (see Sokpor et al, 2018; Stricker and Gotz, 2018, in this Research Topic)
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