Translating neural stem cells to neurons in the mammalian brain

Abstract

The mammalian neocortex underlies our perception of sensory information, performance of motor activities, and higherorder cognition. During mammalian embryogenesis, radial glial precursor cells sequentially give rise to diverse populations of excitatory cortical neurons, followed by astrocytes and oligodendrocytes. A subpopulation of these embryonic neural precursors persists into adulthood as neural stem cells, which give rise to inhibitory interneurons and glia. Although the intrinsic mechanisms instructing the genesis of these distinct progeny have been well-studied, most work to date has focused on transcriptional, epigenetic, and cell-cycle control. Recent studies, however, have shown that posttranscriptional mechanisms also regulate the cell fate choices of transcriptionally primed neural precursors during cortical development. These mechanisms are mediated primarily by RNA-binding proteins and microRNAs that coordinately regulate mRNA translation, stability, splicing, and localization. Together, these findings point to an extensive network of posttranscriptional control and provide insight into both normal cortical development and disease. They also add another layer of complexity to brain development and raise important biological questions for future investigation. Facts • Numerous posttranscriptional regulators including RBPs and miRNAs are expressed in a temporally dynamic and cell-type specific manner during embryonic corticogenesis. • Posttranscriptional mechanisms control cell fate decisions of embryonic and adult neural precursor cells. How do RBPs and miRNAs contribute to neurodevelopmental and neurological disorders?

An Eutherian-Specific microRNA Controls the Translation ofSatb2in a Model of Cortical Differentiation

“…For example, cortical progenitors express Brn1 and Tle4 mRNAs, for both deep and superficial layer fates, respectively, but their translation into the corresponding proteins is initially repressed by a translational repression complex and subsequently released in due time (Zahr et al, 2018). Micro-RNAs are especially interesting in this respect and they have been indicated as heterochronic modulators of vertebrate development (Gulman et al, 2019;Robinton et al, 2019), also in the context of the vertebrate nervous system (Chiu et al, 2014;Nowakowski et al, 2018;Zahr et al, 2019). camo et al, 2008;Britanova et al, 2008).…”

New Insights Into the Intricacies of Proneural Gene Regulation in the Embryonic and Adult Cerebral Cortex

“…This study showed that eukaryotic initiation factor 4E1 (eIF4E1) and the eIF4E-Binding Protein, 4E-T, components of the eukaryotic translational machinery, form P-body-like complexes that bind proneural bHLH mRNAs to inhibit their translation, a mechanism of translational control critical for controlling the timing of cortical neurogenesis ( Yang et al, 2014 ) ( Figure 3A ). Since then, many additional proteins have been identified that control the translation of proneural and neural differentiation genes, including other components of the translational machinery and critical RNA binding proteins ( Amadei et al, 2015 ; Zahr et al, 2018 , 2019 ). Future work will be required to identify specific RNA binding proteins that control the stability and translation of proneural gene transcripts.…”

From structural resilience to cell specification — Intermediate filaments as regulators of cell fate

“…The radial glia will generate neurons during the later stages of neurogenesis as well as astrocytes and oligodendrocytes further during gliogenesis and oligodendrocytogenesis, respectively. 56 In the adult mammalian brain NSCs are found in the ventricular-subventricular zone and the subgranular zone. In addition to NFs, neurons may also express other intermediate filaments such as nestin and vimentin.…”

“…Neurogenesis is initiated early during development when neural stem cells from the neural tube give rise to progenitor cells called radial glia. The radial glia will generate neurons during the later stages of neurogenesis as well as astrocytes and oligodendrocytes further during gliogenesis and oligodendrocytogenesis, respectively 56 . In the adult mammalian brain NSCs are found in the ventricular‐subventricular zone and the subgranular zone.…”