Biology Reference
In-Depth Information
The Eph/Ephrin gradients are an important component of the guidance system that
brings retinal ganglion axons to the optic nerve. Mutant mice that lack EphB function (double
knockouts for EphB2 and EphB3) begin to develop normally but some axons coming from the
dorsal retina defasciculate close to the beginning of the optic nerve, then bypass it and extend
right past it into the opposite side of the eye. In a wild-type embryo, these axons would be
running into a rising gradient of EphB; perhaps carrying on until they perceive enough
EphB is an important part of the growth cones' developmental programme. Or, more realis-
tically, the ratio of Ephrin-B/EphB may be important; a ratio would provide a better scale-
independence for navigating retinas that may be large or small. Alternatively, EphB may
simply be acting as an inhibitory molecule, as it certainly does to retinal growth cones in
culture.
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Axons coming from the dorsal retina will, as they meet more and more EphB on
the cells there, be less and less inclined to migrate on the cells and more inclined to fasciculate
with other axons and therefore enter the nerve with them. In this model, fasciculation will be
driven both by attraction to other axons (L1, Neuropilin, and so on) and repulsion from alter-
native pathways.
Neuropepithelial cells at the point where the optic nerve leaves the eye are a source of
Netrin, while axons of retinal ganglion cells express its receptor, DCC.
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Deletion of Netrin
or DCC function inhibits the ability of axons from all parts of the retina to leave the retina
and follow the optic nerve. In mice, Netrin is expressed along the optic nerve itself,
which presumably makes it attractive to growth cones.
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Additional guidance is provided
by the repulsive molecule Semaphorin 5A, which is expressed in a halo around the netrin-
rich area at the base of the optic nerve and which is assumed to prevent any would-be
escapees from leaving the netrin-rich routes to the nerve
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(
Figure 12.6
).
FIGURE 12.6
A schematic summary of the cues guiding retinal ganglion axons within the retina. Red indicates
repulsive molecules; green and grey indicate attractive molecules.
