Dystroglycan Organizes Axon Guidance Cue Localization and Axonal Pathfinding
Copyright policy )Dystroglycan Organizes Axon Guidance Cue Localization and Axonal Pathfinding
Precise patterning of axon guidance cue distribution is critical for nervous system development. Using a murine forward genetic screen for novel determinants of axon guidance, we identified B3gnt1 and ISPD as required for the glycosylation of dystroglycan in vivo. Analysis of B3gnt1, ISPD, and dystroglycan mutant mice revealed a critical role for glycosylated dystroglycan in the development of several longitudinal axon tracts. Remarkably, the axonal guidance defects observed in B3gnt1, ISPD, and dystroglycan mutants resemble several of the axon guidance defects found in mice lacking the axon guidance cue Slit and its receptor Robo. This similarity is explained by our observations that dystroglycan binds directly to Slit and is required for proper Slit localization within the basement membrane and floor plate in vivo. These findings establish a novel role for glycosylated dystroglycan as a key determinant of axon guidance cue distribution and function in the mammalian nervous system.
- University of California System United States
- Johns Hopkins Medicine United States
- University of Southern California United States
- Johns Hopkins University School of Medicine United States
Central Nervous System, Models, Molecular, Glycosylation, Neuroscience(all), Gene Expression Regulation, Developmental, Mice, Transgenic, Alkaline Phosphatase, Embryo, Mammalian, N-Acetylglucosaminyltransferases, Axons, Mice, Inbred C57BL, Mice, COS Cells, Chlorocebus aethiops, Mutation, Animals, Laminin, Amino Acids, Dystroglycans, Body Patterning, Glycoproteins
Central Nervous System, Models, Molecular, Glycosylation, Neuroscience(all), Gene Expression Regulation, Developmental, Mice, Transgenic, Alkaline Phosphatase, Embryo, Mammalian, N-Acetylglucosaminyltransferases, Axons, Mice, Inbred C57BL, Mice, COS Cells, Chlorocebus aethiops, Mutation, Animals, Laminin, Amino Acids, Dystroglycans, Body Patterning, Glycoproteins
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