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consistent olfactory map is created in the brain (Vassar
et al., 1994; Mombaerts, 1996). There are two major pos-
sibilities. The first is that the expression of a particular
receptor gene is linked to the expression of particular
set of guidance molecules. The other, more radical, pos-
sibility is that the odorant receptor molecules them-
selves are expressed on axonal growth cones and are
involved in sniffing out the correct postsynaptic target
area. Let us look at this more interesting possibility first.
The first question is whether odorant receptor mole-
cules are expressed in axons and growth cones. The
answer is yes, both odorant receptor mRNA and protein
are expressed in growth cones (Barnea et al., 2004)
(Figure 6.26). The next question is what happens when
a receptor is knocked out? Are the axons unable to find
their targets? To answer this question, marker genes
such as lacZ have been knocked into specific receptor
loci. Thus, lacZ is expressed in the cells that would have
expressed a particular receptor and by examining the
distribution of lacZ, which is transported down the
axons of these cells, one can see that the axons appear
disoriented and do not converge on their targets (Wang
et al., 1998). This suggests that the olfactory receptors
are critical for accurate targeting in the bulb.
Swapping receptors is a powerful way to test this
idea (Mombaerts et al., 1996; Wang et al., 1998). Thus,
in another set of experiments, a specific odorant recep-
tor gene was replaced by a fusion gene driving not
only lacZ, but also the cDNA for a different receptor,
M71, so that the axons misexpressing this receptor are
easy to visualize (Figure 6.27). When olfactory neurons
that target to distant regions of the bulb have their
receptors swapped, they target neither to their normal
glomeruli (P2 in this case) nor to the glomeruli typical
of their new odorant receptor (M71). Instead, they map
to a new specific glomerulus somewhere in-between,
suggesting that, although odorant receptors do have
some role in targeting, there must be other factors that
guide these axons to their particular targets. In fact,
there is accumulating evidence that this is so. Like the
muscles of Drosophila larvae discovered above, differ-
ent combinations of cell adhesion and guidance mole-
cules appear to be expressed on various receptors.
However, when receptors are swapped between
sensory neurons that have nearby targets in the same
region such as when the P3 receptor is expressed under
the P2 promoter, the axons do target to the precise
vicinity of P3, proving that the odorant receptors are
very important for targeting to the exact right place.
Even a minor change in the coding region of an
olfactory receptor gene causes a change in the target
destination of the axons that express this gene (Fein-
stein and Mombaerts, 2004). The critical amino acid
residues that affect guidance tend to be clustered in
Olfactory nerve
Olfactory bulb
Olfactory bulb
Mitral cell
Olfactory epithelium
Topographic mapping in visual system (by anatomical axes)
Te c t u m
Topographic mapping in olfactory system (by odorant specificity)
FIGURE 6.25 Comparison of topographic mapping in the visual
system, where neighboring cells project to neighboring targets cre-
ating a central representation of visual space; and the olfactory
system where cells of the same type are intermingled and yet their
axons sort out and converge forming an odor representation map.
same gene map to just one of two of these (Mombaerts,
The zone-to-zone mapping of the olfactory neurons
onto the bulb uses, it seems, guidance cues and topog-
raphy cues that we have already discussed in enough
detail, such as cell adhesion molecules and repulsive
guidance factors. But what concerns us in this case is the
question of how the axons of a single class of receptor
converge onto topographically fixed glomeruli so that a
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