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Pax7
Irx3
Pax6
Olig2
Nkx6.1 Olig2
Nkx2.2 Olig2
FIGURE 2.24 Several genes are expressed in restricted domains in the developing spinal cord; these have
served as useful markers for positional identity of cells in this region of the nervous system. Pax7, Irx3,
and pax6 are all expressed in the intermediate and dorsal regions of the neural tube, while nkx2.2, olig2, and
nkx6.1 are all expressed in the ventral neural tube. Markers like these and others allowed Jessell and col-
leagues to dissect the signals controlling the identity of the different types of neurons in the spinal cord (see
also Chapter 4). (From Wichtele et al., 2002)
from the prechordal mesoderm. Shh represses Pax6 at
the midline and induces pax2 . pax6 and pax2 cross
repress, creating a sharp border between developing
retinal fields ( Pax6 ) and optic stalk region ( Pax2 ) that
separate the developing retinas. When this signal is
interrupted, the eye field remains continuous and a
single eye forms in the midline. The subsequent elab-
oration of the forebrain depends on correct midline
development, and so the lack of Shh disrupts later
stages of brain development as well, leading to a con-
dition known as holoprosencephaly.
The mechanism by which Shh induces ventral
differentiation of the neural tube involves several
interesting signaling steps. In both Drosophila and
vertebrates, the hedgehog proteins undergo autoprote-
olysis to generate an amino-terminal fragment that is
associated with the cell surface and a freely diffusible
carboxyl-terminal fragment. The amino-terminal frag-
ment is sufficient to elicit ventral differentiation as evi-
denced by floorplate and motoneuron differentiation.
Since floorplate differentiation occurs at higher doses
of recombinant Shh and motoneuron differentiation at
lower doses of Shh , it has been proposed that a gradi-
ent of Shh from the notochord and floorplate patterns
the neural tube into these two alternate fates. More will
be said on this topic in Chapter 4.
Although the experiments described with Shh indi-
cate that this molecule can have a profound effect in
ventral patterning of the neural tube, more recent
D
+ Shh
I
V
Precursor
markers
msx1
pax3
Ventral
markers
ISI1
chAT
)
)
FIGURE 2.25 A cell culture system in which the notochord and
the neural tube were co-cultured in collagen gels was used to find
the polarity signal released by mesoderm. The signal was first
shown to be diffusible since pieces of notochord could induce floor-
plate without touching the neural tube. Simply adding recombinant
sonic hedgehog protein to explants of neural tube was sufficient to
induce them to differentiate as ventral neural tissues, including
floorplate and motor neurons. The dorsal-ventral polarity of the
neural tube is controlled in part by a signaling molecule secreted by
the mesodermally derived notochord. In the normal embryo, the
notochord lies just ventral to the neural tube. The cells at the ventral-
most part of the neural tube develop a distinct identity and mor-
phology, and are known as the floorplate (blue). The from embryos
at the time of neural plate formation in chick embryos, no floorplate
develops, and the neural tube fails to develop motoneurons, or other
features of its normal dorsal-ventral polarity. By contrast, if an addi-
tional notochord is transplanted to a more lateral position adjacent
to the neural tube, an additional floorplate develops, and motoneu-
rons are induced to form adjacent to the new floorplate.
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