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.
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.
Sretavan
D W
DW
Departments of Ophthalmology and Physiology, University of California San Francisco, San Francisco, California 94143, USA.
Kruger
K
K
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D004622:Embryo, Mammalian; D007839:Functional Laterality / Q000502:physiology*; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009897:Optic Chiasm / Q000196:embryology*; D012160:Retina / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000378:metabolism
D019922:GAP-43 Protein