Neurogenic niches in the brain: help and hindrance of the barrier systems

Abstract

In the developing central nervous system, most neurogenesis occurs in the ventricular and subventricular proliferative zones. In the adult telencephalon, neurogenesis contracts to the subependyma zone and the dentate gyrus (subgranular zone) of the hippocampus. These restricted niches containing progenitor cells which divide to produce neurons or glia, depending on the intrinsic and environmental cues. Neurogenic niches are characterized by a comparatively high vascular density and, in many cases, interaction with the cerebrospinal fluid (CSF). Both the vasculature and the CSF represent a source of signaling molecules, which can be relatively rapidly modulated by external factors and circulated through the central nervous system. As the brain develops, there is vascular remodeling and a compartmentalization and dynamic modification of the ventricular surface which may be responsible for the change in the proliferative properties. This review will explore the relationship between progenitor cells and the developing vascular and ventricular space. In particular the signaling systems employed to control proliferation, and the consequence of abnormal vascular or ventricular development on growth of the telencephalon. It will also discuss the potential significance of the barriers at the vascular and ventricular junctions in the influence of the proliferative niches.

Keywords: blood-brain barrier; cerebrospinal fluid; cerebrovasculature; choroid plexus; neurogenesis; neurogenic niche; neuronal progenitors.

Figure 1

Dorsal telencephalon in the fetus, showing pial and ventricular vascular plexi and the location of the VZ and SVZ progenitor zones. Microstructure and cellular component of the VZ and SVZ illustrated below, with VZ progenitors contacting the ventricular surface of the brain and SVZ progenitors in close contact with the vascular plexus.

Figure 2

Adult cortex in the mouse, shown from both sagittal and coronal views, indicating the location of the SEZ and SGZ neurovascular niches. The microstructure and cellular component of the SEZ and SGZ are shown underneath. In the SEZ, progenitor cells are in close contact with the CSF and ventricular ependymal cells as well as the vasculature, while the SGZ is restricted to influences from the vasculature. For details on the cell types involved and the molecular characteristics of these cells see the recent review from Fuentealba et al. (2012).