Neural Progenitor Cell Polarity and Cortical Development

Abstract

Neurons populating the cerebral cortex are generated during embryonic development from neural stem and progenitor cells in a process called neurogenesis. Neural stem and progenitor cells are classified into several classes based on the different location of mitosis (apical or basal) and polarity features (bipolar, monopolar and non-polar). The polarized architecture of stem cells is linked to the asymmetric localization of proteins, mRNAs and organelles, such as the centrosome and the Golgi apparatus (GA). Polarity affects stem cell function and allows stem cells to integrate environmental cues from distinct niches in the developing cerebral cortex. The crucial role of polarity in neural stem and progenitor cells is highlighted by the fact that impairment of cell polarity is linked to neurodevelopmental disorders such as Down syndrome, Fragile X syndrome, autism spectrum disorders (ASD) and schizophrenia.

Keywords: apical progenitors; basal progenitors; brain development; epithelial polarity; epithelial to mesenchymal transition (EMT); neural stem and progenitor cells; neurodevelopmental disorders; polarity.

Figure 1

Neural stem and progenitor cell types in the developing neocortex. During early neurogenesis, neuroepithelial cells (NECs) form the ventricular zone (VZ) and are responsible for the lateral expansion of the neocortex. During mid-late neurogenesis, apical progenitors (APs) divide and give rise to basal progenitors (BPs), which form a new proliferative zone, the subventricular zone (SVZ). The APs pool is mainly composed of apical radial glial cells (aRGCs) and a lower proportion of short neural precursors (SNPs) and sub-apical progenitors (SAPs). The BPs pool is composed by intermediate progenitor cells (IPCs) and basal radial glial cells (bRGCs). APs and BPs give rise to neurons that migrate basally and settle in the forming cortical plate (CP). The relative proportion of the different neural stem and progenitor cells changes greatly in species with different encephalyzation and gyrification. APs and BPs generate in a tightly controlled temporal order the pyramidal neurons populating the 6-layered neocortex (not depicted here for simplicity).

Figure 2

Cell polarity and subcellular dynamics in apical radial glial cells. Apical radial glial cells (aRGCs) are highly polarized along their apico-basal axis. The adherens junctions maintain aRGC architecture and tissue integrity at the apical end feet. The basal process contacts the basal lamina with the basal end foot, where several mRNAs are transported and locally translated. The morphology of the basal end feet changes dynamically during neurogenesis. An organelle such as Golgi apparatus (GA) is distributed in the apical process exclusively. On the other hand, the endoplasmic reticulum (ER) is distributed globally in basal and apical processes. aRGC, apical radial glial cell; CP, cortical plate; SVZ, sub-ventricular zone and VZ, ventricular zone (the drawing is adapted from Taverna et al., , licensed under a Creative Commons Attribution 4.0 International License).