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.
Copyright © 2012 Elsevier Inc. All rights reserved.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Alkaline Phosphatase / genetics
-
Alkaline Phosphatase / metabolism
-
Amino Acids / metabolism
-
Animals
-
Axons / metabolism*
-
Body Patterning / genetics
-
Body Patterning / physiology*
-
COS Cells
-
Central Nervous System / cytology*
-
Central Nervous System / embryology
-
Chlorocebus aethiops
-
Dystroglycans / genetics
-
Dystroglycans / physiology*
-
Embryo, Mammalian
-
Gene Expression Regulation, Developmental / genetics
-
Glycoproteins / genetics
-
Glycoproteins / metabolism
-
Glycosylation
-
Laminin / metabolism
-
Mice
-
Mice, Inbred C57BL
-
Mice, Transgenic
-
Models, Molecular
-
Mutation / genetics
-
N-Acetylglucosaminyltransferases / deficiency
-
N-Acetylglucosaminyltransferases / genetics
-
Nerve Tissue Proteins / genetics
-
Nerve Tissue Proteins / metabolism
-
Neural Cell Adhesion Molecule L1 / metabolism
-
Neurofilament Proteins / metabolism
-
Neurons / cytology*
-
Nucleotidyltransferases / genetics
-
Nucleotidyltransferases / metabolism
-
Protein Binding / genetics
-
Receptors, Immunologic / genetics
-
Receptors, Immunologic / metabolism
-
Roundabout Proteins
-
Transfection
Substances
-
Amino Acids
-
Glycoproteins
-
Lamc2 protein, mouse
-
Laminin
-
Nerve Tissue Proteins
-
Neural Cell Adhesion Molecule L1
-
Neurofilament Proteins
-
Receptors, Immunologic
-
dolaisoleucine
-
slit protein, vertebrate
-
Dystroglycans
-
N-Acetylglucosaminyltransferases
-
B4gat1 protein, mouse
-
Nucleotidyltransferases
-
Alkaline Phosphatase