Journal article
Dystroglycan on Radial Glia End Feet Is Required for Pial Basement Membrane Integrity and Columnar Organization of the Developing Cerebral Cortex
Journal of neuropathology and experimental neurology, Vol.71(12), pp.1047-1063
2012
DOI: 10.1097/NEN.0b013e318274a128
PMID: 23147502
Abstract
Interactions between the embryonic pial basement membrane (PBM) and radial glia (RG) are essential for morphogenesis of the cerebral cortex because disrupted interactions cause cobblestone malformations. To elucidate the role of dystroglycan (DG) in PBM-RG interactions, we studied the expression of DG protein and Dag1 mRNA (which encodes DG protein) in developing cerebral cortex and analyzed cortical pheno-types in Dag1 CNS conditional mutant mice. In normal embryonic cortex, Dag1 mRNA was expressed in the ventricular zone, which contains RG nuclei, whereas DG protein was expressed at the cortical surface on RG end feet. Breaches of PBM continuity appeared during early neurogenesis in Dag1 mutants. Diverse cellular elements streamed through the breaches to form leptomeningeal heterotopia that were confluent with the underlying residual cortical plate and contained variably truncated RG fibers, many types of cortical neurons, and radial and intermediate progenitor cells. Nevertheless, layer-specific molecular expression seemed normal in heterotopic neurons, and axons projected to appropriate targets. Dendrites, however, were excessively tortuous and lacked radial orientation. These findings indicate that DG is required on RG end feet to maintain PBM integrity and suggest that cobblestone malformations involve disturbances of RG structure, progenitor distribution, and dendrite orientation, in addition to neuronal “overmigration.”
Details
- Title: Subtitle
- Dystroglycan on Radial Glia End Feet Is Required for Pial Basement Membrane Integrity and Columnar Organization of the Developing Cerebral Cortex
- Creators
- Timothy D MYSHRALL - Department of Comparative Medicine, University of Washington, United StatesSteven A MOORE - Department of Pathology, University of Iowa, Iowa City, Iowa, United StatesAdam P OSTENDORF - Department of Pathology, University of Iowa, Iowa City, Iowa, United StatesJakob S SATZ - Department of Pathology, University of Iowa, Iowa City, Iowa, United StatesTom KOWALCZYK - Department of Neurological Surgery, University of Washington, United StatesHuy NGUYEN - Department of Pathology, University of Iowa, Iowa City, Iowa, United StatesRay A. M DAZA - Seattle Children's Research Institute, Seattle, Washington, United StatesCharmaine LAU - Department of Neurological Surgery, University of Washington, United StatesKevin P CAMPBELL - Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa, United StatesRobert F HEVNER - Department of Neurological Surgery, University of Washington, United States
- Resource Type
- Journal article
- Publication Details
- Journal of neuropathology and experimental neurology, Vol.71(12), pp.1047-1063
- DOI
- 10.1097/NEN.0b013e318274a128
- PMID
- 23147502
- NLM abbreviation
- J Neuropathol Exp Neurol
- ISSN
- 0022-3069
- eISSN
- 1554-6578
- Publisher
- Lippincott Williams & Wilkins; Hagerstown, MD
- Language
- English
- Date published
- 2012
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pathology; Iowa Neuroscience Institute
- Record Identifier
- 9984020779302771
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