The path from the choroid plexus to the subventricular zone: go with the flow!

Abstract

In adult mammals, under physiological conditions, neurogenesis, the process of generating new functional neurons from precursor cells, occurs mainly in two brain areas: the subgranular zone in the dentate gyrus of the hippocampus, and the subventricular zone (SVZ) lining the walls of the brain lateral ventricles. Taking into account the location of the SVZ and the cytoarchitecture of this periventricular neural progenitor cell niche, namely the fact that the slow dividing primary progenitor cells (type B cells) of the SVZ extend an apical primary cilium toward the brain ventricular space which is filled with cerebrospinal fluid (CSF), it becomes likely that the composition of the CSF can modulate both self-renewal, proliferation and differentiation of SVZ neural stem cells. The major site of CSF synthesis is the choroid plexus (CP); quite surprisingly, however, it is still largely unknown the contribution of molecules specifically secreted by the adult CP as modulators of the SVZ adult neurogenesis. This is even more relevant in light of recent evidence showing the ability of the CP to adapt its transcriptome and secretome to various physiologic and pathologic stimuli. By giving particular emphasizes to growth factors and axonal guidance molecules we will illustrate how CP-born molecules might play an important role in the SVZ niche cell population dynamics.

Primary cilia are required in a unique subpopulation of neural progenitors

“…Like radial glia during development, B1-cell apical endings have a primary cilium that projects into the ventricle, which has been suggested to contain signaling factors (24,25). Here we have generated cilia mutant mice using Cre lines driven by Nestin or hGFAP promoters to remove the conditional alleles Kif3a fl/fl and Ift88 fl/− .…”

“…A similar mechanism might be at play in the V-SVZ, given the strategic location of B1 cells' primary cilia. However, the precise origin of Shh destined for the primary cilia in B1 cells remains unknown (24,25,44). It will be interesting to determine whether primary cilia are required for the production of the four recently identified OB interneuron types derived from the AV V-SVZ, a region with high Gli1 expression (42).…”

“…This apical process contains a primary cilium and is surrounded by multiciliated ependymal (E1) cells in a pinwheel-like organization (23). Given their location and the important functions that primary cilia have in the processing of extracellular signals, B1 cells' primary cilia could have key roles in the reception of ventricular signals for the regulation of adult neurogenesis (24,25). However, the function of B1 cells' primary cilia remains unknown.…”

Stroke Repair via Biomimicry of the Subventricular Zone

“…In particular, the CSF is a major supplier of both proteins and small molecules responsible for signaling this niche (Falcão et al, 2012). The choroid plexus determines the composition of CSF in order to directly delivery these proteins and molecules to the SVZ and impact the behavior of neural progenitor cells (Lim et al, 2000;Shen et al, 2008).…”

Intertwining extracellular nucleotides and their receptors with Ca2+in determining adult neural stem cell survival, proliferation and final fate

“…Type B1 cells inherit the apical-basal polarity from their precursors, the embryonic radial glia, with their primary cilium directly contacting the cerebrospinal fluid within the lumen of the ventricles (figure 1b). This structure is considered as essential for the reception of growth factors and morphogens and for the subsequent transduction of signals [10]. Their basal side is in close connection with blood vessels at particular sites where V-SVZ vasculature lacks coverage by both astrocytes and pericytes [11], thus being able to receive regulatory signalling molecules released from endothelial cells or circulating in the blood.…”