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specific tracts in the spinal cord and cerebellum.
In mammals, limbic-associated membrane protein,
LAMP, is an IgCAM expressed by neurons throughout
the limbic system, a cortical and subcortical area of the
brain that functions in emotion and memory (Horton
and Levitt, 1988). Administration of LAMP antibodies
to developing mouse brains results in abnormal
growth of the fiber projections in the limbic system,
suggesting that LAMP is an essential recognition mol-
ecule for the formation of limbic connections (Pimenta
et al., 1995). LAMP has three IgG domains, and these
domains appear to participate in different ways to
enhance local wiring. LAMP enhances neurite out-
growth through homophilic interactions with other
neurons in the limbic circuit using the first of its IgG
domains, but inhibits neurite outgrowth of non-
LAMP-expressing neurons using heterophilic interac-
tions involving the second IgG domain (Eagleson et al.,
2003). The function of the third domain is not known.
Neural cell adhesion molecule (NCAM), the earliest
identified of the CAMs, appears to be expressed on all
vertebrate neurons and glia (Edelman, 1984). NCAM
exists in many different forms, some with an intracel-
lular domain that may interact with the cytoskeleton
and some without. The extracellular portion of NCAM
can be highly modified by the addition of carbohy-
drates, particularly sialic acid residues. Nonsialylated
forms are very adhesive compared to the sialylated
forms. In the course of a neuron's development, there
may be changes in the sialylation state of its NCAM,
thus adjusting its adhesion (Walsh and Doherty, 1997).
For example, developing motor neurons of the chick
grow out of the spinal cord and enter a complicated
plexus region, where they cross in many directions and
eventually segregate into distinct nerve roots leading
to their appropriate muscles. During the time when
these axons are growing in the plexus, the NCAM they
express is highly sialylated. This keeps the axons that
are headed toward different muscles from fasciculat-
ing indiscriminately with one another. If the sialic acid
is digested away with endoneuraminidase (Endo-N),
errors in pathfinding occur in the plexus region, and
motor axons exit into the wrong peripheral nerves
(Tang et al., 1994) (Figure 5.22).
Growing axons respond to a variety of cues as they
navigate, so the loss of just one of these may affect
axon growth and navigation in a limited way. In many
gene deletion studies in Drosophila , there is a signifi-
cant increase in pathfinding errors, but the majority of
axons usually grow along the correct pathway. For
instance, in fasII mutants mentioned above, although
longitudinal tracts are somewhat defasciculated, the
axons are still able to grow in the correct directions. In
some CAM knockouts, for instance the NCAM knock-
Spinal cord
Nerve root
Nerve branch
FIGURE 5.22 Homophilic adhesion is regulated by polysialic
acid. A. The brachial plexus region in the chick where motor axons
destined for particular muscles sort out into their correct nerve roots.
B. Higher magnification of the plexus region showing fascicles
breaking up and axons regrouping with other axons. C. After treat-
ment with Endo-N to remove sialic acid residues from N-CAM, the
axons do not defasciculate properly and stay in large fascicles. As a
result, innervation errors are made. (After Tang et al., 1994)
out in the mouse, the phenotype is surprisingly subtle,
suggesting that it is just one of a number of molecules
that are used for this purpose. This idea of molecular
redundancy for pathfinding in the developing nervous
system is supported by the finding that sometimes
doubly mutant embryos, which have deletions of more
than one particular adhesion molecule, exhibit severe
axonal growth defects, whereas each of the single
mutants is relatively normal. For example, Drosophila
that lack FasciclinI, a CAM that is expressed in com-
missural fascicles, have a normal looking CNS. To test
whether FasI is part of a redundant system, a series of
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