Loss of Col3a1, the Gene for Ehlers-Danlos Syndrome Type IV, Results in Neocortical Dyslamination
MetadataShow full item record
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.
CitationPLoS One. 2012 Jan 3; 7(1):e29767
- Biallelic COL3A1 mutations result in a clinical spectrum of specific structural brain anomalies and connective tissue abnormalities.
- Authors: Horn D, Siebert E, Seidel U, Rost I, Mayer K, Abou Jamra R, Mitter D, Kornak U
- Issue date: 2017 Sep
- Bi-allelic variants in <i>COL3A1</i> encoding the ligand to GPR56 are associated with cobblestone-like cortical malformation, white matter changes and cerebellar cysts.
- Authors: Vandervore L, Stouffs K, Tanyalçin I, Vanderhasselt T, Roelens F, Holder-Espinasse M, Jørgensen A, Pepin MG, Petit F, Khau Van Kien P, Bahi-Buisson N, Lissens W, Gheldof A, Byers PH, Jansen AC
- Issue date: 2017 Jun
- Ehlers-Danlos syndrome type IV is associated with a novel G984R COL3A1 mutation.
- Authors: Deng Y, Wei S, Hu S, Chen J, Tan Z, Yang Y
- Issue date: 2015 Jul
- G protein-coupled receptor 56 and collagen III, a receptor-ligand pair, regulates cortical development and lamination.
- Authors: Luo R, Jeong SJ, Jin Z, Strokes N, Li S, Piao X
- Issue date: 2011 Aug 2
- A new COL3A1 mutation in Ehlers-Danlos syndrome type IV.
- Authors: Eder J, Laccone F, Rohrbach M, Giunta C, Aumayr K, Reichel C, Trautinger F
- Issue date: 2013 Mar