Slit1/2 and Robo1/2 knockout mice when compared to heterozygous controls. Mutant SN-VTA axons spread out in the diencephalon to form a wider tract. Phenotypes included invasion of the ventral midline, consistent with Slit repulsion. However, individual axons also wandered in aberrant dorsal trajectories, which suggests an unexpected role for Slits. Based on these and previous results we suggest that Slit/Robo signaling is necessary for correct dorsal/ ventral positioning and precise pathfinding of dopaminergic longitudinal axons, as well as serving a repellant function. These results may provide important insights into treatment of degeneration of SN-VTA dopminergic fibers in Parkinson's and Alzheimer's disease.
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