GENERATION OF
NEURONAL DIVERSITY IN THE SPINAL CORD AND HINDBRAIN
The neural stem cells in the spinal
cord and hind brain can be divided into four broad classes: motor
neurons and related interneuron progenitors, sensory relay neurons and related
interneuron progenitors, glial cell progenitors, and neural crest progenitors. There
are key distinctions for each of these four classes. The first two stem cell
classes, motor and sensory progenitors, have the capacity to give rise to both
projection neurons with long axons that connect either the spinal cord with
muscles and autonomic ganglia (motor) or send their axons from the spinal cord
to higher brain regions to relay sensory information (sensory). These stem
cells can also give rise to multiple classes of interneurons, whose axons
remain in close proximity to the position of the interneuron cell body and
which tend to establish inhibitory control for motor or sensory projection
neurons. For these classes of stem cells (and the related intermediate
progenitors), most cell division happens in the ventricular/marginal zone. The
newly generated neuroblasts are then displaced over small distances so
that they acquire an appropriate position in the dorsal or anterior horn. In
the hindbrain, there is some local cell migration between distinct
anterior-posterior locations (defined by the segmental organization of
rhombomeres that prefigures the morphogenesis of the hindbrain) that leads to greater diversity of
cells within cranial nerve motor or sensory relay nuclei. The third class of
stem cells gives rise to the glia in the spinal cord and hindbrain. These stem
cells are indistinguishable from the neurepithelial progenitors that
give rise to neurons, and indeed they are mostly multipotent: they give rise to
neurons as well as glial cells.
The specification and subsequent
generation and differentiation of glial progeny are distinct from those of
neurons. For the most part, the three primary classes of glia—astrocytes,
oligodendroglial cells (see below), and radial glia are generated later than the neurons of the
spinal cord and hindbrain. Astrocytes are further differentiated into two
classes: (1) protoplasmic astrocytes, which are found primarily adjacent
to neuronal cell bodies and their processes, where they collectively constitute
the neuropil (gray matter), and (2) fibrous astrocytes, which are found
primarily in axon tracts (white matter) and whose processes often contact blood
vessels. Radial glial resemble neuroepithelial progenitors, and indeed may be
indistinguishable from these cells in many ways. A small number of radial glial
cells remain in the mature ependymal zone in many regions, and these cells,
when placed in appropriate cell culture conditions, can generate neurons as
well as astrocytes and oligodendroglial. Thus the radial glia seem to either be
neural stem cells or at least retain neural stem cell capacity that can be
expressed under distinctive experimental conditions. Oligodendroglial cells interact with axons to
generate the myelin sheaths that ensure efficient conduction of action
potentials (see Plate 1-19). Oligodendroglial precursors initially are
generated at the anterior midline and rely on some of the same secreted
signaling molecules and transcription factors that also influence motor neuron
determination and differentiation. Subsequently, however, oligodendroglial
precursors are found throughout the developing and mature brain, and they can
either retain their progenitor capacity (and in some cases, when isolated and
cultured, can give rise to neurons as well as glia) or they can generate local
myelinating oligodendroglia.
The fourth class of neural stem cell
generated from the neural tube that gives rise to the spinal cord and hindbrain
is the neural crest progenitor. As mentioned above, these stem cells
either generate intermediate progenitors that then give rise to postmitotic migrating
neuroblasts that actively move, or migrate, short distances from the
neural tube and then reaggregate to form the sensory ganglia, including
posterior root ganglia and most of the cranial nerves. Some sensory ganglion
cells have a single cell body with a single process that bifurcates into a
peripheral receptor process and central presynaptic process. This polarity
facilitates generating receptor potentials in the periphery that also initiate
action potentials that are conducted toward the CNS, where sensory information
is then relayed via synapses made by the central process of the sensory
ganglion cell. The neural crest also generates a truly bipolar sensory ganglion
cell, the bipolar sensory ganglion cells of the spiral ganglion
(auditory), or Scarpa’s ganglion (vestibular). These neurons have a distinct
post-synaptic process that receives synapses from auditory or vestibular hair
cells and a central process that relays sensory information by making synapses
made in the cochlear nucleus or vestibular nucleus in the hindbrain. The neural
crest–derived neuroblasts also coalesce to form the autonomic ganglia of
the sympathetic chain as well as the more widely distributed parasympathetic
ganglia. Finally, neural crest–derived neuroblasts give rise to the neurosecretory
adrenal chromaffin cells found in the adrenal medulla. The neural crest
also gives rise to significant populations of migrating progenitor cells that
divide further at their destinations. These include mesenchymal neural crest
cells that populate the head and craniofacial primordia and give rise to the
meninges (arachnoid, pia, and dura), some local blood vessel– associated cells,
and multiple skeletal elements, including teeth and cranial bones. In addition,
pigment cells in the epidermis are derived from migratory neural crest
progenitors. Finally, the major class of peripheral glial cells, the Schwann
cells, which have characteristics similar to oligodendroglia in the CNS, is
derived from the neural crest.
