Abstract
The development of the cerebral cortex relies on different types of progenitor cell. Among them, the recently described basal radial glial cell (bRG) is suggested to be of critical importance for the development of the brain in gyrencephalic species. These cells are highly numerous in primate and ferret brains, compared to lissencephalic species such as the mouse in which they are few in number. Their somata are located in basal subventricular zones in gyrencephalic brains and they generally possess a basal process extending to the pial surface. They sometimes also have an apical process directed toward the ventricular surface, similar to apical radial glial cells (aRGs) from which they are derived, and whose somata are found more apically in the ventricular zone. bRGs share similarities with aRGs in terms of gene expression (SOX2, PAX6, and NESTIN), whilst also expressing a range of more specific genes (such as HOPX). In primate brains, bRGs can divide multiple times, self-renewing and/or generating intermediate progenitors and neurons. They display a highly specific cytokinesis behavior termed mitotic somal translocation. We focus here on recently identified molecular mechanisms associated with the generation and amplification of bRGs, including bRG-like cells in the rodent. These include signaling pathways such as the FGF-MAPK cascade, SHH, PTEN/AKT, PDGF pathways, and proteins such as INSM, GPSM2, ASPM, TRNP1, ARHGAP11B, PAX6, and HIF1α. A number of these proteins were identified through transcriptome comparisons in human aRGs vs. bRGs, and validated by modifying their activities or expression levels in the mouse. This latter experiment often revealed enhanced bRG-like cell production, even in some cases generating folds (gyri) on the surface of the mouse cortex. We compare the features of the identified cells and methods used to characterize them in each model. These important data converge to indicate pathways essential for the production and expansion of bRGs, which may help us understand cortical development in health and disease.
Highlights
The cerebral cortex is the seat of complex brain functions and is a highly organized and compartmentalized structure
Stahl et al (2013) overexpressed Trnp1 in the mouse using in utero electroporation and showed an enrichment of Pax6+ APs at the expense of the generation of Tbr2+ basal progenitors (BPs) at E16, and knocking down the gene induced the amplification of Tbr2+ cells in the subventricular zone (SVZ), and most importantly of cells carrying the hallmarks of typical human basal radial glial cell (bRG) 3 days after electroporation
This review offers a comprehensive view on bRGs, including mechanisms and genes currently described as being involved in their generation, their characteristics in terms of morphology and function as well as their role in the gyrification of the cortex
Summary
The cerebral cortex is the seat of complex brain functions and is a highly organized and compartmentalized structure. The authors showed that expression via in utero electroporation at E14 of constitutively active forms of Fgfr1 (a tyrosine kinase receptor known to activate the pathway), Mek (a MAP kinase) or Etv4 (a response gene of the MAPK pathway) all lead to increased generation of Hopx+/Pax6+/Sox2+ bRG-like cells in the mouse 2 days later, and these cells can produce neurons and astrocytes (Heng et al, 2017).
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