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The Journal of Neuroscience, December 15, 1998, 18(24):10502-10513
Randomized Retinal Ganglion Cell Axon Routing at the Optic Chiasm
of GAP-43-Deficient Mice: Association with Midline Recrossing and Lack
of Normal Ipsilateral Axon Turning
David W.
Sretavan and
Kelly
Kruger
Departments of Ophthalmology and Physiology, University of
California San Francisco, San Francisco, California 94143
During mammalian development, retinal ganglion cell (RGC) axons
from nasal retina cross the optic chiasm midline, whereas temporal
retina axons do not and grow ipsilaterally, resulting in a projection
of part of the visual world onto one side of the brain while the
remaining part is represented on the opposite side. Previous studies
have shown that RGC axons in GAP-43-deficient mice initially fail to
grow from the optic chiasm to form optic tracts and are delayed
temporarily in the midline region. Here we show that this
delayed RGC axon exit from the chiasm is characterized by abnormal
randomized axon routing into the ipsilateral and contralateral optic
tracts, leading to duplicated representations of the visual world in
both sides of the brain. Within the chiasm, individual contralaterally
projecting axons grow in unusual semicircular trajectories, and the
normal ipsilateral turning of ventral temporal axons is absent. These
effects on both axon populations suggest that GAP-43 does not mediate
pathfinding specifically for one or the other axon population but is
more consistent with a model in which the initial pathfinding defect at
the chiasm/tract transition zone leads to axons backing up into the
chiasm, resulting in circular trajectories and eventual random axon
exit into one or the other optic tract. Unusual RGC axon trajectories
include chiasm midline recrossing similar to abnormal CNS midline
recrossing in invertebrate "roundabout" mutants and
Drosophila with altered calmodulin function. This
resemblance and the fact that GAP-43 also has been proposed to regulate
calmodulin availability raise the possibility that calmodulin function
is involved in CNS midline axon guidance in both vertebrates and invertebrates.
Key words:
GAP-43; retinal ganglion cell; axon pathfinding; calmodulin; optic chiasm; optic tract; ventral diencephalon midline; growth cone signaling
Copyright © 1998 Society for Neuroscience 0270-6474/98/182410502-12$05.00/0
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