The SVZ stem cell niche-components, functions, and in vitro modelling

Abstract

Neocortical development depends on the intrinsic ability of neural stem and progenitor cells to proliferate and differentiate to generate the different kinds of neurons in the adult brain. These progenitor cells can be distinguished into apical progenitors, which occupy a stem cell niche in the ventricular zone and basal progenitors, which occupy a stem cell niche in the subventricular zone (SVZ). During development, the stem cell niche provided in the subventricular zone enables the increased proliferation and self-renewal of basal progenitors, which likely underlie the expansion of the human neocortex. However, the components forming the SVZ stem cell niche in the developing neocortex have not yet been fully understood. In this review, we will discuss potential components of the SVZ stem cell niche, i.e., extracellular matrix composition and brain vasculature, and their possible key role in establishing and maintaining this niche during fetal neocortical development. We will also emphasize the potential role of basal progenitor morphology in maintaining their proliferative capacity within the stem cell niche of the SVZ. Finally, we will focus on the use of brain organoids to i) understand the unique features of basal progenitors, notably basal radial glia; ii) study components of the SVZ stem cell niche; and iii) provide future directions on how to improve brain organoids, notably the organoid SVZ, and make them more reliable models of human neocortical development and evolution studies.

Keywords: ECM; basal progenitors; neocortex development; stem cell niche; subventricular zone; vasculature.

FIGURE 1

Overview of the components of SVZ stem cell niche in the developing neocortex. A developing cortical wall including all major cell types of a representative gyrencephalic mammal, such as human or ferret (middle panel). The ECM components and growth factors in the basal lamina can be detected by the cell surface receptors at the basal end-feet of bRG, including integrins and Notch (top left panel). Blood vessels secrete factors that may be received by basal progenitors in the SVZ. Basal progenitors can also establish contacts with basal lamina of the blood vessels, which may provide an additional source for signaling molecules (bottom left panel). The extracellular environment in the SVZ contains specific ECM proteins (e.g., TNC), receptor ligands (e.g., PTN, LIF) and growth factors (e.g., FGF). These components that are detected by bRG cell surface receptors, such as PTPRZ1 and LIFR, may activate intracellular signaling pathways to promote bRG proliferation (bottom right panel).