71bridge suggest the possibility that some of the progenitors detach from the CC and
invade the cellular bridge (Rehermann et al. 2009 ).
Cells belonging to the bridge matrix also behave as oligodendrocyte precursors
and/or premyelinating oligodendrocytes (Levine et al. 2001 ) enveloping regenerat-
ing axons. Then, it is likely that analogous phenomena may occur in the embryonic-
like microenvironment supporting neural repair in the turtle spinal cord.
The emerging view when comparing data from turtles with those obtained from
anamniotes is that in the latter the ependymal layer as a whole, has retained some
properties of the embryonic neural tube. For example, in Xenopus tadpoles there is
a close axonal-ependymal association during early stages of the regeneration pro-
cess (Michel and Reier 1979 ) and in axolotls the cells lining the CC regenerate the
spinal cord inducing a multipotent blastema (Schnapp et al. 2005 ; Tanaka and
Ferreti 2009 ). In turtles, however, the bridge region lacks a distinguishable CC. The
BLBP+ cells of the ependymal layer appear as the most likely candidate to give rise
to the abundant pre-myelinating oligodendrocytes that envelop the incoming axons.
The origin and functional role of GFAP+ cells in the cellular bridge is still uncer-
tain. However, unlike in mammals, GFAP+ cells do not interfere with regenerating
axons because they appear aligned with axon bundles. Therefore, turtles appear as a
unique amniote model system occupying a peculiar intermediate place between the
anamniotes with complete regenerating capabilities and mammals, with very
restricted capabilities to restore damaged spinal circuitry.
How tissue damage can activate ependymal cells to trigger endogenous repair
remains a fundamental issue to solve. Experiments performed in zebrafish indicate
that regenerative properties seem to be linked to a protein encoded by the connective
tissue growth factor that helps forming a glial bridge allowing the transit of growing
axons through the lesion site (Mokalled et al. 2016 ). In contrast, our recent wide
scale genome study performed in the turtle Trachemys scripta elegans showed the
“absence of a group of genes exclusive of regenerating taxa” suggesting that ana-
tomical and functional recovery results from cellular and molecular mechanisms
involving the “expression patterns of genes shared by all amniotes” (Valentin-Kahan
et al. 2017 ).
Although mammals lost the ability for self-repair, some cells in the CC still react
to injury by proliferating and migrating toward the lesion (Beattie et al. 1997 ;
Johansson et al. 1999 ; Mothe and Tator 2005 ), where most become astrocytes within
the core of the scar (Meletis et al. 2008 ). However, a number of ependyma-derived
cells become oligodendrocytes that interact with axonal sprouts (Meletis et al.
2008 ). Ependyma-derived cells seem to play a central role in the formation of the
scar thereby limiting the extension of damage (Sabelström et al. 2013 ). Astrocyte-
like and oligodendrocyte-like cells derived from the ependyma concentrate in the
core of the scar and release growth factors that improve the survival of neurons
around the lesion (Sabelström et al. 2013 ). However, a recent report casts some
doubts about the actual contribution of ependymal cells to scar formation (Ren et al.
2017 ) suggesting that more research is needed to understand the potential of the CC
as a source for repair.
5 Spinal Cord Stem Cells In Their Microenvironment: The Ependyma as a Stem Cell...