57(Li et al. 2016 ). Ependymal cells in the mouse spinal cord continue dividing postna-
tally to become quiescent 9 weeks after birth (Sabourin et al. 2009 ).
Besides ependymal cells, a particular type of neuron contributes to the lining of
the CC. The presence of cells with neuronal characteristics in this area was pro-
posed by studies conducted at the beginning of the last century (reviewed by Vigh-
Teichmann and Vigh 1983 ). They were called cerebrospinal fluid contacting neurons
(CSFcNs) because their peculiar morphology with a prominent process that con-
tacts the CC lumen (Vigh and Vigh-Teichmann 1998 ; Vigh et al. 1977 , 1983 ) and
their cell bodies located sub-ependymally. Pioneering studies performed in the rat
spinal cord showed that neurogenesis is only present during the period between E11
and E16 (Nornes and Das 1972 , 1974 ). The production of CSFcNs in the rat spinal
cord starts in E12 and is maintained until E22, peaking between E14 and E15 (Kutna
et al. 2014 ). CSFcNs have intriguing features (described in detail below) resembling
immature neurons in adult neurogenic niches (Marichal et al. 2009 ). In the mouse
spinal cord, CSFcNs are produced from two distinct dorsoventral regions during
embryonic life. Most CSFcNs derive from progenitors circumscribed to the late-p2
and the oligodendrogenic (pOL, called pMN during the early neurogenic period, see
above) domains, whereas a second subset of CSFcNs arises from cells bordering the
FP (Petracca et al. 2016 ). These cells start to be generated at E10 and continue to
arise until E14–E16, a developmental stage in which most spinal neurons have been
already produced.
Taken together, both ependymal cells and neurons contacting the CC seem to be
generated in late stages of spinal cord development, a fact that may be related with
the postnatal maintenance of some peculiar anatomical, molecular and functional
features of embryonic progenitors and neuroblasts.
5.3 The Nature of Neural Stem Cells
The first progenitors in the neural tube are neuroephitelial cells which at the onset
of neurogenesis become radial glia (RG), the founders of most neurogenic lineages
during development (Kriegstein and Alvarez-Buylla 2009 ). Both neuroepithelial
cells and RG have a pronounced polarity with an apical pole bearing a single pri-
mary cilium protruding into the ventricular lumen and a distal process in contact
with the pia (Kriegstein and Alvarez-Buylla 2009 ). This polarity is critical to deter-
mine and regulate the phenotype of neural stem cells (Alvarez-Buylla et al. 2001 ;
Pinto and Götz 2007 ). For example, the apical pole of RG contains components like
the centrosome and various key proteins (e.g., prominin, PAR3) whose inheritance
during division determines the fate of daughter cells. In the adult mammalian brain,
it is currently accepted that progenitors are a subtype of astrocyte (called B cells)
that retain key features of both neuroepithelial cells and RG (Doetsch et al. 1997 ;
Horner and Palmer 2003 ; Ming and Song 2005 ; Lledo et al. 2006 ; Lim et al. 2008 ).
The cell bodies of B cells in the subventricular zone (SVZ) are intermingled with
multiciliated ependymal cells. Each B cell exhibits an irregular process bearing a
5 Spinal Cord Stem Cells In Their Microenvironment: The Ependyma as a Stem Cell...