Biology Reference
In-Depth Information
FIGURE 12.4
The change in receptor expression in commisural axons once they have crossed the midline.
The use of Netrin, Slit and Robo proteins in regulating crossing of the midline is strongly
conserved phylogenetically. Although the CNS of vertebrates has a quite different morph-
ology to that of insects, and vertebrate genomes contain families of netrin, slit and robo genes,
they use them in essentially the same way and suffer similar errors of axon guidance if the
genes are mutated.
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A problem related to that of ignoring the influence of an already reached waypoint is
that of becoming newly responsive to the next waypoint in the sequence. In the verte-
brate spinal cord, commissural axons grow down towards the floorplate of the spinal
cord, cross its midline and then grow up the other side until they meet the correct
longitudinal fibre tract. Once they have found this tract, they turn and grow along it.
In a normal spinal cord, they ignore the presence of a similar longitudinal tract on
the side of the spinal cord from which they originate, suggesting that they gain interest
only once they have passed the midline waypoint. In chick embryos, commissural axons
heading towards their midline crossing express no EphA2 but they do express it as soon
as they have passed the midline, and continue to do so when they are in the longitu-
dinal fibre tract (the ventral funiculus). The expression of the protein is quite specific
to those parts of the axon beyond the midline crossing and is not seen on the parts
of the axon between the cell body and the midline, suggesting that EphA2 is being
inserted into the membrane by the growth cone only after it has passed the midline.
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There is now good biochemical evidence that protein synthesis can take place locally at
growth cones
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and a highly conserved 3' untranslated sequence from EphA2 mRNA
can drive expression of reporter proteins in the same growth cone-specific, post-
midline-specific manner. The signalling events that take place at the growth cone to
switch on synthesis of specific new mRNAs have not yet been worked out, but in prin-
ciple local protein synthesis may prove to be a key mechanism in waypoint navigation.
Being local, it would also allow multiple growth cones emanating from the same cell
(for example, those of a dendritic arbour) to make their own independent decisions
about where to go.
