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6.3.1.4 Cell-ECM Interactions
NSCs express low levels of ECM receptors such as integrin-α 6 β1, syndecan-1 and
Lutheran, but their expression rises significantly when they become mitotically
active and remains high in proliferating progenitors (Kazanis et al. 2010 ). When
integrin-α 6 β1 function is disturbed in vivo by intracerebroventricular infusion of
blocking antibodies, progenitors move away of BVs and their proliferation increases
(Kazanis et al. 2010 ; Shen et al. 2008 ). We and others have shown that NSCs and
local astrocytes produce many of the laminins, the tenascin-C and the chondroitin/
dermatan sulfate chains that surround them within the SEZ (Akita et al. 2008 ;
Kazanis et al. 2007 , 2010 ). In addition, highly organized extravascular 3D struc-
tures, formed by laminins, collagen IV, heparan sulfates and perlecan, that are called
fractones, have been shown to connect the meninges with the ependymal cell layer
(Mercier et al. 2002 ). Fractones are in direct contact with NSCs and their progeny
and a significant aspect of their function is to sequester and capture growth factors
and morphogens such as FGF2 and BMP-4 (Douet et al. 2013 ; Kerever et al. 2007 ;
Mercier and Douet 2014 ). Recently, another ECM component, called anosmin-1,
was described to be of importance in regulating NSC proliferation through its bind-
ing to FGFR1 (García-González et al. 2016 ).
When type A cells migrate towards the olfactory bulbs through the rostral migra-
tory stream, they do so within corridors rich in ECM components, such as laminins
and tenascin-C, formed by specialized astrocytes and in close contact with BVs
(Bovetti et al. 2007b; Todd et al. 2017 ). Their organized migration is controlled by
cell-ECM interactions and is facilitated by the expression of matrix metalloprotein-
ases by neuroblasts (Bovetti et al. 2007a). Defective β1 or β8-integrin function
impairs migration (Belvindrah et al. 2007b; Mobley and McCarty 2011 ), overex-
pression of anosmin-1 enhances it (García-González et al. 2016 ) and the interaction
between laminin-γ1 chains and soluble netrin-4 (produced by astrocytes) is neces-
sary for the activation of integrin signalling (Staquicini et al. 2009 ). As soon as
neuroblasts reach their target area they migrate tangentially and differentiate into
interneurons, a process controlled by another ECM component, Tenascin-R (David
et al. 2013 ). The mess frequent oligodendroglial progenitors produced by NSCs,
migrate towards the corpus callosum again in close contact with BVs and under the
control of netrin (Cayre et al. 2013 ).
6.3.1.5 Diffusible Factors
The extremely complicated processes that take place within the SEZ stem cell niche
are controlled and co-ordinated by a vast range of factors, operating in small volume
and at the same time. In most of the cases we don’t know in detail the source of
these factors, nor the exact way their activity is tuned with each other. An important
morphogen during embryonic development of the nervous system is Sonic
Hedgehog (Shh). It has been shown to control proliferation of activated NSCs (in
culture it shortens both G 1 and S-G 2 /M phases) and by knocking out its receptor
E. Andreopoulou et al.