Journal article
Distinct functions of glial and neuronal dystroglycan in the developing and adult mouse brain
The Journal of neuroscience, Vol.30(43), pp.14560-14572
10/27/2010
DOI: 10.1523/JNEUROSCI.3247-10.2010
PMCID: PMC2979314
PMID: 20980614
Abstract
Cobblestone (type II) lissencephaly and mental retardation are characteristic features of a subset of congenital muscular dystrophies that include Walker-Warburg syndrome, muscle-eye-brain disease, and Fukuyama-type congenital muscular dystrophy. Although the majority of clinical cases are genetically undefined, several causative genes have been identified that encode known or putative glycosyltransferases in the biosynthetic pathway of dystroglycan. Here we test the effects of brain-specific deletion of dystroglycan, and show distinct functions for neuronal and glial dystroglycan. Deletion of dystroglycan in the whole brain produced glial/neuronal heterotopia resembling the cerebral cortex malformation in cobblestone lissencephaly. In wild-type mice, dystroglycan stabilizes the basement membrane of the glia limitans, thereby supporting the cortical infrastructure necessary for neuronal migration. This function depends on extracellular dystroglycan interactions, since the cerebral cortex developed normally in transgenic mice that lack the dystroglycan intracellular domain. Also, forebrain histogenesis was preserved in mice with neuron-specific deletion of dystroglycan, but hippocampal long-term potentiation was blunted, as is also the case in the Largemyd mouse, in which dystroglycan glycosylation is disrupted. Our findings provide genetic evidence that neuronal dystroglycan plays a role in synaptic plasticity and that glial dystroglycan is involved in forebrain development. Differences in dystroglycan glycosylation in distinct cell types of the CNS may contribute to the diversity of dystroglycan function in the CNS, as well as to the broad clinical spectrum of type II lissencephalies.
Details
- Title: Subtitle
- Distinct functions of glial and neuronal dystroglycan in the developing and adult mouse brain
- Creators
- Jakob S Satz - Howard Hughes Medical Institute, and Department of Molecular Physiology, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa 52242, USAAdam P OstendorfShangwei HouAmy TurnerHajime KusanoJane C LeeRolf TurkHuy NguyenSusan E Ross-BartaSteve WestraToshinori HoshiSteven A MooreKevin P Campbell
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.30(43), pp.14560-14572
- Publisher
- United States
- DOI
- 10.1523/JNEUROSCI.3247-10.2010
- PMID
- 20980614
- PMCID
- PMC2979314
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Grant note
- R21 NS041407 / NINDS NIH HHS U54 NS053672 / NINDS NIH HHS U54 NS053672-05 / NINDS NIH HHS Howard Hughes Medical Institute R21 NS041407-03 / NINDS NIH HHS
- Language
- English
- Date published
- 10/27/2010
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pathology; Iowa Neuroscience Institute; Obstetrics and Gynecology
- Record Identifier
- 9984020722502771
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