title: α6 integrin subunit regulates cerebellar development.
abstract: Mutations in genes encoding several basal lamina components as well as their cellular receptors disrupt normal deposition and remodeling of the cortical basement membrane resulting in a disorganized cerebral and cerebellar cortex. The α6 integrin was the first α subunit associated with cortical lamination defects and formation of neural ectopias. In order to understand the precise role of α6 integrin in the central nervous system (CNS), we have generated mutant mice carrying specific deletion of α6 integrin in neuronal and glia precursors by crossing α6 conditional knockout mice with Nestin-Cre line. Cerebral cortex development occurred properly in the resulting α6 (fl/fl;nestin-Cre) mutant animals. Interestingly, however, cerebellum displayed foliation pattern defects although granule cell (GC) proliferation and migration were not affected. Intriguingly, analysis of Bergmann glial (BG) scaffold revealed abnormalities in fibers morphology associated with reduced processes outgrowth and altered actin cytoskeleton. Overall, these data show that α6 integrin receptors are required in BG cells to provide a proper fissure formation during cerebellum morphogenesis.
authors.affiliation: IGBMC Institut de Génétique et de Biologie Moléculaire et Cellulaire, Department of Development and Stem Cells, CNRS UMR7104, Inserm U964, Université de Strasbourg, Illkirch, France. giovanni.marchetti@unice.fr
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marchetti
authors.forename: Adèle
authors.initials: A
authors.lastname: De Arcangelis
authors.forename: Véronique
authors.initials: V
authors.lastname: Pfister
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Georges-Labouesse
mesh_terms: D008841:Actin Cytoskeleton; D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D002531:Cerebellum / Q000166:cytology / Q000196:embryology* / Q000254:growth & development*; D018507:Gene Expression Regulation, Developmental; D039503:Integrin alpha6 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis; D009457:Neuroglia / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D039503:Integrin alpha6; D012333:RNA, Messenger
keywords: Bergmann glial cell; cerebellar foliation; cerebellum; integrin; laminin