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 wo rld onto one side of the brain while the remaining part is represented on t he opposite side. Previous studies have shown that RGC axons in GAP-43-defi cient mice initially fail to grow from the optic chiasm to form optic tract s and are delayed temporarily in the midline region. Here we show that this delayed RGC axon exit from the chiasm is characterized by abnormal randomi zed axon routing into the ipsilateral and contralateral optic tracts, leadi ng to duplicated representations of the visual world in both sides of the b rain. Within the chiasm, individual contralaterally projecting axone grow i n unusual semicircular trajectories, and the normal ipsilateral turning of ventral temporal axons is absent. These effects on both axon populations su ggest 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 init ial pathfinding defect at the chiasm/tract transition zone leads to axons b acking up into the chiasm, resulting in circular trajectories and eventual random axon exit into one or the other optic tract. Unusual RGC axon trajec tories include chiasm midline recrossing similar to abnormal CNS midline re crossing in invertebrate "roundabout" mutants and Drosophila with altered c almodulin function. This resemblance and the fact that GAP-43 also has been proposed to regulate calmodulin availability raise the possibility that ca lmodulin function is involved in CNS midline axon guidance in both vertebra tes and invertebrates.