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dc.contributor.authorJeong, Sung-Jin
dc.contributor.authorLi, Shihong
dc.contributor.authorLuo, Rong
dc.contributor.authorStrokes, Natalie
dc.contributor.authorPiao, Xianhua
dc.contributor.editorMei, Lin
dc.date.accessioned2012-10-26T16:29:35Z
dc.date.available2012-10-26T16:29:35Z
dc.date.issued2012-01-3en_US
dc.identifier.citationPLoS One. 2012 Jan 3; 7(1):e29767en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid22235340en_US
dc.identifier.doi10.1371/journal.pone.0029767en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/692
dc.description.abstractIt has recently been discovered that Collagen III, the encoded protein of the type IV Ehlers-Danlos Syndrome (EDS) gene, is one of the major constituents of the pial basement membrane (BM) and serves as the ligand for GPR56. Mutations in GPR56 cause a severe human brain malformation called bilateral frontoparietal polymicrogyria, in which neurons transmigrate through the BM causing severe mental retardation and frequent seizures. To further characterize the brain phenotype of Col3a1 knockout mice, we performed a detailed histological analysis. We observed a cobblestone-like cortical malformation, with BM breakdown and marginal zone heterotopias in Col3a1-/- mouse brains. Surprisingly, the pial BM appeared intact at early stages of development but starting as early as embryonic day (E) 11.5, prominent BM defects were observed and accompanied by neuronal overmigration. Although collagen III is expressed in meningeal fibroblasts (MFs), Col3a1-/- MFs present no obvious defects. Furthermore, the expression and posttranslational modification of a-dystroglycan was undisturbed in Col3a1-/- mice. Based on the previous finding that mutations in COL3A1 cause type IV EDS, our study indicates a possible common pathological pathway linking connective tissue diseases and brain malformations.
dc.rightsJeong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.subjectResearch Articleen_US
dc.subjectBiologyen_US
dc.subjectBiochemistryen_US
dc.subjectCytochemistryen_US
dc.subjectExtracellular Matrixen_US
dc.subjectProteinsen_US
dc.subjectMolecular Cell Biologyen_US
dc.subjectCellular Typesen_US
dc.subjectExtracellular Matrixen_US
dc.subjectNeuroscienceen_US
dc.subjectMedicineen_US
dc.subjectAnatomy and Physiologyen_US
dc.subjectNeurological Systemen_US
dc.subjectNeurologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBasement Membraneen_US
dc.subject.meshCollagen Type IIIen_US
dc.subject.meshEhlers-Danlos Syndromeen_US
dc.subject.meshGene Deletionen_US
dc.subject.meshHumansen_US
dc.subject.meshInterneuronsen_US
dc.subject.meshMiceen_US
dc.subject.meshNeocortexen_US
dc.subject.meshNeurogliaen_US
dc.titleLoss of Col3a1, the Gene for Ehlers-Danlos Syndrome Type IV, Results in Neocortical Dyslaminationen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3250483en_US
dc.contributor.corporatenameDepartment of Neurology
dc.contributor.corporatenameCollege of Graduate Studies
refterms.dateFOA2019-04-10T00:33:14Z
html.description.abstractIt has recently been discovered that Collagen III, the encoded protein of the type IV Ehlers-Danlos Syndrome (EDS) gene, is one of the major constituents of the pial basement membrane (BM) and serves as the ligand for GPR56. Mutations in GPR56 cause a severe human brain malformation called bilateral frontoparietal polymicrogyria, in which neurons transmigrate through the BM causing severe mental retardation and frequent seizures. To further characterize the brain phenotype of Col3a1 knockout mice, we performed a detailed histological analysis. We observed a cobblestone-like cortical malformation, with BM breakdown and marginal zone heterotopias in Col3a1-/- mouse brains. Surprisingly, the pial BM appeared intact at early stages of development but starting as early as embryonic day (E) 11.5, prominent BM defects were observed and accompanied by neuronal overmigration. Although collagen III is expressed in meningeal fibroblasts (MFs), Col3a1-/- MFs present no obvious defects. Furthermore, the expression and posttranslational modification of a-dystroglycan was undisturbed in Col3a1-/- mice. Based on the previous finding that mutations in COL3A1 cause type IV EDS, our study indicates a possible common pathological pathway linking connective tissue diseases and brain malformations.


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