Stem Cell Microenvironments and Beyond

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6.3 The NSC Microenvironment of the Postnatal CNS


Contrary to the assumption that neurogenesis in mammals is completed by the end
of the embryonic period, experiments continuously demonstrate that small scale
NSC activity occurs in the adult brain as well. NSC-driven cell generation in the
adult CNS is detected primarily in two specialized microenvironments: the Sub-
Ependymal Zone of the lateral walls of the lateral ventricles (SEZ, also known as
Ventricular-SVZ) and the Sub-Granular Zone (SGZ) of the dentate gyrus of the
hippocampus (general review in (Kazanis 2012 , 2013 ). According to the unified
hypothesis of the lineage of NSCs, a fraction of RGCs during early postnatal stages
gives rises to adult NSCs (Alvarez-Buylla et al. 2001 ). The SEZ is populated mostly
by NSCs of ventral telencephalon origin, although some cortical origin has also
been demonstrated (Willaime-Morawek et al. 2006 ), while the SGZ is populated by
NSCs having migrated from the ventral hippocampus (Li et al. 2013 ).


6.3.1 In the Subependymal Zone


6.3.1.1 The SEZ System


The SEZ is located at the lateral walls of the lateral ventricles of the brain and NSCs
cluster between BVs and the monolayer of ependymal cells that separate it from the
ventricle (Fig. 6.1a, c). It contains quiescent NSCs, various progenitor types, dif-
ferentiated cells and vessels and, due to its specific cytoarchitecture and its anatomi-
cal restriction, it is called a neurogenic niche. NSCs of astoglial morphology (also
called B1 cells) divide rarely and asymmetrically to self-renew and to generate tran-
sit amplifying cells (type C cells) (Doetsch et al. 1999 ). Type B1 cells are the most
multipotent cells of the SEZ and can exist in a quiescent or activated state (Mich
et al. 2014 ; Pastrana et al. 2009 ). Type C cells then divide symmetrically approxi-
mately three times before becoming type A cells (Ponti et al. 2013 ). The more com-
mitted progeny of type C cells are: (a) type A cells (or neuroblasts) that are of
neuronal commitment, express doublecortin and PSA-NCAM and migrate as chains
towards the olfactory bulbs via the rostral migrtaory stream (RMS) where they dif-
ferentiate into interneurons and contribute to the olfaction (Lazarini et al. 2014 ). (b)
Oligodendrogenic precursor cells that migrate to the corpus callosum (Etxeberria
et al. 2010 ; Kazanis et al. 2017 ).


6.3.1.2 Ependyma, Choroid Plexus and Cerebrospinal Fluid


The highly specialized architecture of the SEZ enables specific cell-cell interactions
and the local activity of important modulators of NSC behaviour. Type B1 cells
have small processes which penetrate the ependymal layer and communicate with
the ventricle and longer processes that maintain contact with BVs (Mirzadeh et al.


E. Andreopoulou et al.
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