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Neural ridges
The vertebrate spinal cord is composed of a variety
of cell types, including motor neurons, local interneu-
rons, and projection neurons. The embryonic spinal
cord even contains a set of sensory neurons, called
Rohon-Beard cells. These cells die by adult stages, and
sensory input to the spinal cord is supplied by dorsal
root ganglion neurons. The spinal cord primordium
begins as a rectangular sheet of neural plate epithelium
centered above the notochord. Lineage tracing experi-
ments show that cells in the lateral edges of plate tend
to give rise to Rohon-Beard cells and dorsal interneu-
rons, while cells in the medial plate tend to give rise to
motor neurons and ventral interneurons (Hartenstein,
1989) (Figure 4.23). Occasional clones are composed of
different cell types, so it is thought that local position,
rather than lineage, is involved in the generation of
neuronal diversity in the spinal cord.
As we saw in Chapter 2, tissues outside the nervous
system often provide critical signals that influence
development within the CNS. In that chapter, we also
reviewed the evidence that the notochord played a key
role in establishing the dorsal-ventral axis of the neural
tube, by providing a source of Shh. In this section, we
will see how the same signal from the notochord is crit-
ical for spinal neuron differentiation acting as an
organizing center for the induction of cell fate (Jessell
et al., 1989). As we saw in the previous chapter, Shh
secreted by the notochord induces the neural plate
cells that are directly above to become the floorplate of
the spinal cord. Once the floorplate has been induced
in the ventral spinal cord, Shh signaling is relayed by
the floorplate into the ventral neural tube. The ventro-
lateral region of the tube that gives rise to motoneu-
rons sees a fairly high dose of Shh , while further
dorsally, where interneurons develop, the dose of Shh
is lower. In response to this single gradient of Shh,
several different neuronal types are generated. The
most ventral neurons require the highest doses of Shh ,
and successively more dorsal ones require corre-
spondingly less. When Shh is missing as in a knockout
or is antagonized with an antibody, there is no floor-
plate, nor any ventral neuronal type in the spinal cord.
When intermediate regions of the cord are exposed to
higher levels of Shh , cells there take on more ventral
fates, such as motor neurons.
How do cells at different dorso-ventral levels inter-
pret their exposure to different levels of Shh to acquire
different fates? Jessell and colleagues (Jessell, 2000)
have shown that particular threshold levels of Shh turn
on some homeodomain genes (Class II) and turn off
Neural plate
Spinal region
Neural crest
Primary sensory
(RB cell)
FIGURE 4.23 Rows of primary neurons in the neural plate. The
most lateral row gives rise to sensory neurons (Rohon Beard Cells),
the middle row gives rise to interneurons, and the most medial row
gives rise to primary motor neurons. (After Hartenstein, 1989)
others (Class I). Thus, the read-out of the Shh level is
first registered in neural tube neurons by expression of
specific homeodomain proteins, which are either
turned on or off at particular Shh thresholds (Figure
4.24). In this way, the ventral boundaries of Class I
expression and the dorsal boundaries of Class II
expression set up unique domains. The boundaries
between these domains are sharpened through cross-
repression of the two classes of genes. For example if
the ventral border of the Class I Pax-6 gene overlaps the
dorsal boarder of the Class II Nkx2.2 gene, cross-repres-
sion sets in, so that only one of these genes is expressed
in any particular domain. By this process, specific
domains uniquely express particular combinations of
Class I and Class II homeodomain transcription factors.
This results in spatial coordinates along the DV axis
that are very similar to those used in setting up the
mediolateral coordinate genes in Drosophila . Indeed,
the Drosophila mediolateral coordinate genes share
homologies with these vertebrate dorso-ventral neural
tube genes, suggesting a conserved coordinate system.
Motor neurons arise from the domain that uniquely
expresses Nkx6.1 but not Irx3 and Nkx2.2. Nkx6.1,
unhindered by the repressive activities of these other
factors, turns on OLIG2, a bHLH transcription factor
that is required for motor neuron differentiation.
OLIG2 in turn activates the expression of motor neuron
specific transcription factors such as Mnr2, Hb9, Lim3,
and Isl1/2. Once expressed, Mnr2 can regulate its own
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