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Dystroglycan organizes axon guidance cue localization and axonal pathfinding.

Neuron | Dec 6, 2012

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.

Pubmed ID: 23217742 RIS Download

Mesh terms: Alkaline Phosphatase | Amino Acids | Animals | Axons | Body Patterning | COS Cells | Central Nervous System | Cercopithecus aethiops | Dystroglycans | Embryo, Mammalian | Gene Expression Regulation, Developmental | Glycoproteins | Glycosylation | Laminin | Mice | Mice, Inbred C57BL | Mice, Transgenic | Models, Molecular | Mutation | N-Acetylglucosaminyltransferases | Nerve Tissue Proteins | Neural Cell Adhesion Molecule L1 | Neurofilament Proteins | Neurons | Nucleotidyltransferases | Protein Binding | Receptors, Immunologic | Transfection

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Associated grants

  • Agency: NINDS NIH HHS, Id: NS062047
  • Agency: NINDS NIH HHS, Id: NS34814
  • Agency: NIGMS NIH HHS, Id: R01 GM099321
  • Agency: NINDS NIH HHS, Id: R01 NS034814
  • Agency: NINDS NIH HHS, Id: R01 NS062047
  • Agency: NICHD NIH HHS, Id: R01HD055545
  • Agency: Howard Hughes Medical Institute, Id:

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