56
potential stem cell niche sharing some features with those in the brain has gained
ground. In this chapter, we focus on the properties of cells within this spinal cord
stem cell niche in mammals and non-mammalian vertebrates. We first overview the
current knowledge about the developmental origin of the cells that line the CC. Next,
we address their morphological, molecular and functional properties in the postna-
tal spinal cord and discuss the potential of ependymal cells isolated from their natu-
ral microenvironment. We finally review recent data on the signals that modulate the
biology of cells within this niche and discuss the reaction of ependymal cells in
diverse models of spinal cord injuries or pathologies with implications for
self-repair.
5.2 The Origin of Cells Within the CC Niche
In the caudal portion of the neural tube, progenitors are organized in dorso-ventral
spatial domains (Jessell 2000 ; Briscoe et al. 2000 ) that initially produce distinct
types of neurons to later generate oligodendrocytes and astrocytes. Six ventral
domains can be identified in the ventral part of the neural tube based on the combi-
natorial expression of various transcription factors (ventral to dorsal): the floor plate
domain (FP, Foxa2,Shh), p3 (Nkx2.2, Nkx6.1), pMN (Olig2, Pax6, Nkx6.1), p2
(Nkx6.1, Pax6, Irx3), p1 (Dbx2, Nkx6.2, Pax6, IrX3), and p0 (Dbx1, Dbx2, Pax6,
Irx3) (p meaning progenitor and MN motoneuron; Briscoe et al. 2000 ; Lee and Pfaff
2001 ; Dessaud et al. 2008 ). The study of the dynamic expression of neural progeni-
tor genes in distinct domains of the neuroepithelium indicate that adult ependymal
cells arise from progenitors in the pMN and p2 domains, as they retain expression
of Nkx6.1 (p3, pMN and p2 domains) but not Nkx2.2 (p3 domain) (Fu et al. 2003 ).
Moreover, lineage-tracing experiments using a tamoxifen-inducible Cre-
recombinase inserted into the Olig2 locus demonstrated that some ependymal cells
are produced within the pMN domain (Masahira et al. 2006 ). More recent experi-
ments with different transgenic Cre-recombinase expressing mice support the view
that the mature ependymal region in the spinal cord comprises cells with different
embryonic origins: dorsal ependymal cells originate from the embryonic p2 domain
whereas ventral cells derive from pMN progenitors (Yu et al. 2013 ).
The exact timing of birth of ependymal cells has been explored with 5-bromo- 2-
deoxyuridine pulses applied at different stages of embryonic life and various sur-
vival periods. In the brain, the majority of ependymal cells appeared to be generated
between E14 and E16 and derived from radial glial cells (Spassky et al. 2005 ). In
the spinal cord, they seem to appear later. Most ependymal cells in the rat originate
initially around E18 and continue until postnatal days 8 and 15 (Sevc et al. 2011 ).
The increment in cell number accompanies the closure and transformation of the
primitive lumen into the post-embryonic CC. The transcription factor FoxJ1 in the
brain is involved in the differentiation of ependimocytes from radial glia (Jacquet
et al. 2009 ). A recent study using a FoxJ1-CreER transgenic mouse dates the earliest
birth of ependymal cells at E15.5 with the CC fully populated by these cells at P10
N. Marichal et al.