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Journal of Neuroscience, Vol 10, 1995-2007, Copyright © 1990 by Society for Neuroscience
Specific routing of retinal ganglion cell axons at the mammalian optic chiasm during embryonic development
DW Sretavan
Laboratory of Neurobiology, Rockefeller University, New York, New York 10021.
During development of the mammalian CNS, axons encounter multiple pathway
choices on their way to central target structures. A major pathway branch
point in the visual system occurs at the optic chiasm, where retinal
ganglion cell axons may either enter the ipsilateral or the contralateral
optic tract. To investigate whether embryonic mouse retinal ganglion cell
axons, upon reaching the optic chiasm, selectively grow into the correct
pathway, developing retinal ganglion cells were retrogradely labeled using
either 1,1'-dioctadecyl- 3,3,3',3'-tetramethylindocarbocyanine perchlorate
(Dil) or fluorescent microspheres placed into the optic tract on one side.
The distribution of ipsilaterally and contralaterally projecting ganglion
cells in the embryo was then examined and compared to that of the adult
animal. Results show that axon routing at the chiasm is already extremely
adult- like as early as embryonic day 15 (E15), shortly after retinal axons
arrive at the chiasm. [Retinal ganglion cell neurogenesis = E11-E18
(Drager, 1985); birth = E21.] Throughout the development of this pathway,
routing errors are infrequent and are on the order of only about 3-8/1000
retinal ganglion cells. Thus, embryonic retinal ganglion cell axons do not
project randomly at the optic chiasm but instead appear to be highly
specific in their choice of pathway. To learn how correct pathway choices
are made, retinal axons were retrogradely labeled with Dil and their
trajectories at the optic chiasm were reconstructed. Results show that
ipsilaterally and contralaterally projecting axons are highly intermixed as
they enter the chiasm region but selectively grow into the correct pathway.
For example, a contralaterally projecting axon near the entrance of the
ipsilateral optic tract will turn and bypass this pathway and grow towards
the midline to head into the contralateral optic tract. Similarly, axons
far away from the ipsilateral optic tract frequently turn abruptly at right
angles to enter the ipsilateral tract, directly crossing over
contralaterally projecting axons heading to the opposite side. The sorting
out of intermixed ipsilaterally and contralaterally projecting retinal
axons into the appropriate optic tracts strongly suggests the presence of
specific guidance cues at the optic chiasm during embryonic development.
Together, results from this study demonstrate that the pattern of axon
projection at the adult mammalian optic chiasm is gradually built upon a
highly specific pattern of axon routing laid down early during development.
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