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the ETS family of transcription factors. For example,
the ETS gene ER81 is expressed in the motor neurons
that innervate the limb adductor muscle in chicks,
while the iliotrochanter motor neurons express the
PEA3 ETS gene. Recent work suggests that these ETS
genes regulate the expression of cell adhesion and axon
guidance factors that help motor neurons recognize
their targets (Price et al., 2002). Interestingly, the
sensory afferents that innervate the stretch receptors in
particular muscles express the same ETS gene as the
motor neurons that innervate those muscles (Lin et al.,
1998), and this helps the sensory neuron axons find
the dendrites of these motor neurons completing the
monosynaptic stretch reflex (Chen et al., 2003). Limb
ablation studies show that signals from the periphery,
perhaps from the muscles themselves, help establish
the pattern of ETS gene expression in the sensory
neurons that innervate particular muscles (Figure 4.26).
As described in Chapter 3, there are two main types of
glial cells in the brain, the astrocytes and the oligoden-
drocytes. The oligodendrocytes are the cells of the verte-
brate CNS that produce myelin sheaths around axons.
While early views of CNS development proposed
that these cells could arise throughout the CNS, we
now know that these cells arise from relatively restricted
domains in the ventral regions of the brain, and then
they migrate to the axon tracts throughout the brain
(Figure 4.27). Several years ago, it was discovered that a
specific growth factor, PDGF, is a mitogen for the oligo-
dendrocyte precursors in the spinal cord. Subsequent
work demonstrated that the receptor for this mitogen,
the PDGFa, is specifically expressed in a restricted
domain of the neural tube that gives rise to the oligo-
dendrocytes. It was therefore not too surprising that
when several groups reported cloning oligodendrocyte-
specific transcription factors, Olig1 and Olig2, these
factors were expressed in the same ventral domain as
the PDGF receptor. But what was very surprising was
that the domain of Olig1/2 expression was the same
domain from where motoneurons were arising! How do
the same progenitors make both motoneurons and
oligodendrocytes? The answer lies again in the chang-
ing competence of the progenitors. The cells that express
Olig1 initially also express neurogenin2 (Nrgn2), a tran-
scription factor that is similar to the other proneural
bHLH transcription factors (Kessaris et al., 2001; Zhou et
al., 2001). During the time when the cells in this region of
the spinal cord express both Nrgn2 and Olig1, these pro-
genitors generate motoneurons. During the same time
that these cells are making motoneurons, the zone of
olig1 is dorsal to the zone of Nkx2.2 expression. Later in
development, the zone of Nkx2.2 moves dorsally to
overlap with the Olig1/2 domain, while the Nrgn2
expression domain moves further dorsally and now no
Sensory neuron
Cell body
Muscle spindle
Axon of
motor neuron
Motor neuron
Stretch reflex arc
sensory axon
limb muscle
limb muscle
dorsal limb
motor axon
No ETS expression
FIGURE 4.26 Matching sensory motor connectivity determined
by muscles. A and B. Spindle afferents terminate on homonymous
motor neurons. C. If the sensory fibers that normally innervate
ventral muscles are forced to innervate dorsal muscles, they switch
synaptic partners to the motor neurons that normally innervate
dorsal muscles. D. Different muscles seem to induce the particular
ETS molecules on both the motor and sensory neurons that inner-
vate it. Thus, the motor and sensory neurons that innervate the
Adductor muscle express the ETS ER81 molecule. E. If the periph-
eral muscles are removed, the motor and sensory neurons no longer
express ETS molecules. (After Lin et al., 1998)
longer overlaps with the Olig1/2 expression domain. At
this point in time, the progenitors that express both
olig1/2 and nkx2.2 now start making oligodendrocytes.
Experimentally misexpressing olig2 along with ngn2
causes the progenitors to produce motoneurons, whereas
misexpressing olig2 and nkx2.2 causes the progenitors
to produce oligodendrocytes. In olig2 knockout mice,
neither oligodendrocytes nor motor neurons develop.
In this chapter we have looked at the cellular deter-
mination in several different systems and have seen
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