Biology Reference
In-Depth Information
the Ephrin-B2/EphB1 system is demonstrated by the phenotype of EphB1 mutant mice,
which show very little ipsilateral projection.
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Choice of the ipsilateral pathway by axons
from the left eye is aided by the presence of axons from the right eye that have
already crossed to follow the left side of the body, and vice versa. Animals in which one
eye is missing show a reduced number of ipsilateral axons even when EphB1 is being
expressed normally.
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The influence of axons from the contralateral eye may be due to
general attractive surface molecules such as L1, without which they are less able to support
ipsilateral choices by axons from the other eye.
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The need for the opposite eye to exist for
ipsilateral projection to take place creates an interesting adaptive response in the embryo,
given that it makes sense for it not to bother creating pathways for binocular vision when
one eye is missing. It is probably an 'accidental' adaptive ability, though, as it is hard to
see how it would be selected directly in evolution.
Once they are through the optic chiasm, axons have to find their appropriate target cells in
the optic tectum, an area of the midbrain. The arrangement of axons that terminate on the
tectum transforms the continuous spatial map of the retina to a corresponding continuous
(albeit differently shaped) spatial map on the tectum. It has been known for over 40
years that this mapping depends on specific biochemical cues borne by axons and tectum.
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One set of cues is provided, once again, by the Eph/Ephrin signalling system. The optic
tectum expresses Ephrins-A2 and -A5 in a gradient with high expression in the posterior
of the tectum and lower expression in the anterior, the Ephrin-A5 gradient being steeper
60,61
(
Figure 12.8
). The nasal retina projects to the posterior tectum and the temporal retina
projects to the anterior tectum, intermediate positions on the retinal naso-temporal axis pro-
jecting to correspondingly intermediate positions on the tectal antero-posterior axis. There is
therefore a correspondence between the gradients of Ephrins-A2 and -A5 expressed by the
retina and those gradients in the tectum: axons from a zone of retina with high Ephrin-A2
project to regions of tectum with high Ephrin-A2 and vice versa.
Retinal axons express EphA3, a receptor for Ephrins-A2 and -A5, in a gradient that is high
in the temporal region and low nasally. Since binding of A type Ephrins by EphAs exerts
a repulsive influence on growth cones (see Chapter 11), these expression patterns strongly
suggest a mechanism in which retinotectal mapping is mediated by repulsion. Repulsion
is maximal when expression of both EphA3 and Ephrin-A2/5 is highest, so temporal axons
are repelled most strongly from posterior retina. They will still be repelled, but less strongly,
from regions of tectum less posterior. Similarly, axons originating from intermediate loca-
tions on the naso-termporal axis will express less EphA3 and will be repelled less than
temporal axons are by the same level of Ephrin-A2/5. If space on the tectum were infinite,
the repulsion would steer almost all axons to the anterior since almost all would be repelled
to some extent by posterior tectum. Space is not infinite, however, and axons have to compete
with each other. The mapping is therefore caused by a combination of graded repulsion with
competition. The model presented above predicts that the antero-posterior map of the tectum
will be lost if expression of Ephrins-A2 and -A5 is prevented, and this is exactly what has
been observed.
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Competition implies that the 'decision' made by an axon about when to terminate is not
a once-and-for-all affair, and detailed observations of the developing visual system have
shown that the initial places that axons seem to decide to stop growing are often inaccurate.
Generally they overshoot their final locations and later correct themselves either by turning
