Document Detail


Dystroglycan on radial glia end feet is required for pial basement membrane integrity and columnar organization of the developing cerebral cortex.
MedLine Citation:
PMID:  23147502     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 phenotypes 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."
Authors:
Timothy D Myshrall; Steven A Moore; Adam P Ostendorf; Jakob S Satz; Tom Kowalczyk; Huy Nguyen; Ray A M Daza; Charmaine Lau; Kevin P Campbell; Robert F Hevner
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of neuropathology and experimental neurology     Volume:  71     ISSN:  1554-6578     ISO Abbreviation:  J. Neuropathol. Exp. Neurol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-30     Completed Date:  2013-02-04     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  2985192R     Medline TA:  J Neuropathol Exp Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1047-63     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Age Factors
Animals
Basement Membrane* / cytology,  embryology,  metabolism
Bromodeoxyuridine / metabolism
Cell Movement / genetics
Cell Proliferation
Cerebral Cortex / cytology*,  embryology*
Dystroglycans / genetics,  metabolism*
Embryo, Mammalian
Female
Gene Expression Regulation, Developmental / genetics*
In Situ Nick-End Labeling
Intermediate Filament Proteins / deficiency
Male
Mice
Mice, Knockout
Nerve Tissue Proteins / deficiency,  metabolism
Nestin
Neuroglia / cytology*
Neurons / physiology
RNA, Messenger / metabolism
Repressor Proteins / metabolism
Stem Cells / physiology
Tumor Suppressor Proteins / metabolism
Grant Support
ID/Acronym/Agency:
5 T32 RR07019/RR/NCRR NIH HHS; R01 NS050248/NS/NINDS NIH HHS; R01 NS050248-04/NS/NINDS NIH HHS; R21 NS041407/NS/NINDS NIH HHS; R21 NS041407/NS/NINDS NIH HHS; T32 RR007019/RR/NCRR NIH HHS; U54 NS053672/NS/NINDS NIH HHS; U54 NS053672/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Bcl11b protein, mouse; 0/Intermediate Filament Proteins; 0/Nerve Tissue Proteins; 0/Nes protein, mouse; 0/Nestin; 0/RNA, Messenger; 0/Repressor Proteins; 0/Tumor Suppressor Proteins; 146888-27-9/Dystroglycans; G34N38R2N1/Bromodeoxyuridine
Comments/Corrections

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