Journal article
Glial scaffold required for cerebellar granule cell migration is dependent on dystroglycan function as a receptor for basement membrane proteins
Acta neuropathologica communications, Vol.1(1), pp.58-58
2013
DOI: 10.1186/2051-5960-1-58
PMCID: PMC3893534
PMID: 24252195
Abstract
Background: Cobblestone lissencephaly is a severe neuronal migration disorder associated with congenital muscular dystrophies (CMD) such as Walker-Warburg syndrome, muscle-eye-brain disease, and Fukuyama-type CMD. In these severe forms of dystroglycanopathy, the muscular dystrophy and other tissue pathology is caused by mutations in genes involved in O-linked glycosylation of alpha-dystroglycan. While cerebellar dysplasia is a common feature of dystroglycanopathy, its pathogenesis has not been thoroughly investigated. Results: Here we evaluate the role of dystroglycan during cerebellar development. Brain-selective deletion of dystroglycan does not affect overall cerebellar growth, yet causes malformations associated with glia limitans disruptions and granule cell heterotopia that recapitulate phenotypes found in dystroglycanopathy patients. Cerebellar pathology in these mice is not evident until birth even though dystroglycan is lost during the second week of embryogenesis. The severity and spatial distribution of glia limitans disruption, Bergmann glia disorganization, and heterotopia exacerbate during postnatal development. Astrogliosis becomes prominent at these same sites by the time cerebellar development is complete. Interestingly, there is spatial heterogeneity in the glia limitans and granule neuron migration defects that spares the tips of lobules IV-V and VI.
Conclusions: The full spectrum of developmental pathology is caused by loss of dystroglycan from Bergmann glia, as neither granule cell- nor Purkinje cell-specific deletion of dystroglycan results in similar pathology. These data illustrate the importance of dystroglycan function in radial/Bergmann glia, not neurons, for normal cerebellar histogenesis. The spatial heterogeneity of pathology suggests that the dependence on dystroglycan is not uniform.
Details
- Title: Subtitle
- Glial scaffold required for cerebellar granule cell migration is dependent on dystroglycan function as a receptor for basement membrane proteins
- Creators
- Huy Nguyen - Department of Pathology, 4270A Carver Biomedical Research Building, The University of Iowa, 285 Newton Road, Iowa City, IA 52242, USAAdam P Ostendorf - Department of Pathology, 4270A Carver Biomedical Research Building, The University of Iowa, 285 Newton Road, Iowa City, IA 52242, USAJakob S Satz - Department of Molecular Physiology and Biophysics, Internal Medicine, and Neurology, The University of Iowa, Iowa City, IA 52242, USASteve Westra - Department of Pathology, 4270A Carver Biomedical Research Building, The University of Iowa, 285 Newton Road, Iowa City, IA 52242, USASusan E Ross-Barta - Department of Pathology, 4270A Carver Biomedical Research Building, The University of Iowa, 285 Newton Road, Iowa City, IA 52242, USAKevin P Campbell - Department of Molecular Physiology and Biophysics, Internal Medicine, and Neurology, The University of Iowa, Iowa City, IA 52242, USASteven A Moore - Department of Pathology, 4270A Carver Biomedical Research Building, The University of Iowa, 285 Newton Road, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Acta neuropathologica communications, Vol.1(1), pp.58-58
- DOI
- 10.1186/2051-5960-1-58
- PMID
- 24252195
- PMCID
- PMC3893534
- NLM abbreviation
- Acta Neuropathol Commun
- ISSN
- 2051-5960
- eISSN
- 2051-5960
- Publisher
- BioMed Central
- Language
- English
- Date published
- 2013
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pathology; Iowa Neuroscience Institute
- Record Identifier
- 9984020614502771
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