title: Dystroglycan organizes axon guidance cue localization and axonal pathfinding.
abstract: 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.
authors.affiliation: The Solomon H. Snyder Department of Neuroscience and Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Wright
authors.forename: Krissy A
authors.initials: KA
authors.lastname: Lyon
authors.forename: Haiwen
authors.initials: H
authors.lastname: Leung
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Leahy
authors.forename: Le
authors.initials: L
authors.lastname: Ma
authors.forename: David D
authors.initials: DD
authors.lastname: Ginty
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism*; D019521:Body Patterning / Q000235:genetics / Q000502:physiology*; D019556:COS Cells; D002490:Central Nervous System / Q000166:cytology* / Q000196:embryology; D002522:Chlorocebus aethiops; D049030:Dystroglycans / Q000235:genetics / Q000502:physiology*; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006031:Glycosylation; D007797:Laminin / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D017351:N-Acetylglucosaminyltransferases / Q000172:deficiency / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology*; D009713:Nucleotidyltransferases / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D000097905:Roundabout Proteins
chemical_list: D000469:Alkaline Phosphatase; D000596:Amino Acids; D049030:Dystroglycans; D006023:Glycoproteins; D007797:Laminin; D017351:N-Acetylglucosaminyltransferases; D009419:Nerve Tissue Proteins; D039842:Neural Cell Adhesion Molecule L1; D016900:Neurofilament Proteins; D009713:Nucleotidyltransferases; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; C498522:Lamc2 protein, mouse; C098463:dolaisoleucine; C120566:slit protein, vertebrate; C530032:B4gat1 protein, mouse