912008 ; Tavazoie et al. 2008 ). We have suggested that ependymal cells are an impor-
tant component of the niche, since their number is correlated with the number of
NSCs and the ependymal expression on noggin (a BMP inhibitor) facilitates neuro-
genesis (Kazanis and ffrench-Constant 2012 ; Lim et al. 2000 ). CSF is constantly
produced by the choroid plexus (CP), a monolayer of epithelial cells that lie on a
highly vascularized stroma, floating within the brain ventricles (Marques et al.
2016 ). The adult human has about 150 mL of CSF which is renewed 2–3 times per
day and NSCs remain in contact with the CSF which contains multiple soluble fac-
tors which modulate NSC properties (Delgado et al. 2014 ; Lehtinen et al. 2011 ; Lun
et al. 2015 ; Silva-Vargas et al. 2016 ). The synthesis of CSF is controlled by mecha-
nisms such as the blood-CSF barrier formed by the CP epithelial cells and the blood
flow which in the CP is five times higher than that in the brain parenchyma.
Comprehensive analysis of the adult CP transcriptome and secretome, both under
physiological conditions and in disease (Marques et al. 2016 ; Silva-Vargas et al.
2016 ; Thouvenot et al. 2006 ), has unraveled the expression of several genes encod-
ing key molecules known to modulate NSCs. Among these are insulin-like growth
factor 2, several members of the fibroblast growth factor family, epidermal growth
factor, transforming growth factor alpha, platelet-derived growth factors, bone mor-
phogenetic proteins, sonic hedgehog, Wnts and axon guidance molecules such as
Slits. Notably, the transcriptome of the CP changes significantly during adulthood;
as a consequence, NSC medium conditioned with early postnatal CP is pro-
proliferative for NSCs, but becomes anti-proliferative when conditioned with adult
CP (Silva-Vargas et al. 2016 ).
6.3.1.3 Vasculature
As described above, type B1 cells retain a process connecting them with BVs of the
neurogenic niche. NSC quiescence is controlled through direct cell contact with
endothelial cells, via ephrinB2 and Jagged1 signalling (Ottone et al. 2014 ) and via
diffusible factors such as neurotrophin-3 (Delgado et al. 2014 ). Moreover, the che-
mokine stromal-derived factor 1 (SDF-1) is expressed in endothelial cells and
recruits type B1 and C cells into the vascular plexus via chemotaxis (Kokovay et al.
2010 ). Endothelial cells also secrete an EGF-like growth factor, called Betacellulin,
which activates EGFRs on type B1 and C cells and ErbB-4 receptors on neuroblasts.
It is therefore suggested that betacellulin acts in vivo on early as well as later stages
of the SEZ neurogenic lineage and its role is the promotion of SEZ cell proliferation
and OB neurogenesis (Gómez-Gaviro et al. 2012 ). Notably, the architecture of the
vasculature within the SEZ presents specialized features, when compared with other
periventricular areas, such as its higher density, its penetration very proximal to the
ependymal layer and its higher levels of leakage (Culver et al. 2013 ; Kazanis et al.
2010 ; Tavazoie et al. 2008 ). Finally, the transit amplifying progenitors in the SEZ,
similar to intermediate progenitors in the SVZ of the developing cortex, are posi-
tioned and undergo mitosis very close to BVs and especially at domains that lack
pericytes and astrocytic endfeet (Shen et al. 2008 ; Tavazoie et al. 2008 ).
6 Being a Neural Stem Cell: A Matter of Character But Defined...