title: Proper cerebellar development requires expression of β1-integrin in Bergmann glia, but not in granule neurons.
abstract: β1-class integrins play essential roles both in developmental biology as well as in cancer. Particularly, a Nestin-driven deletion of β1-integrin receptors results in severe abnormalities of brain development including a laminar disorganization of cerebellar granule neurons. However, since Nestin is expressed in all kinds of neural precursors, these data do not allow conclusions to be drawn about the role of β1-integrins in distinct neuronal and glial cell types. By generating conditional knockout mice using granule cell-specific Math1-promoter sequences, we show here that the expression of β1-integrins in granule neurons is dispensable for the development of the cerebellum. Also, deletion of β1-integrin from tumors that arise in a mouse model of granule cell precursor-derived medulloblastoma did not result in a significant survival benefit. Last, expression levels of β1-integrin in human medulloblastoma samples did not predict patient's outcome. However, a β1-integrin knockout using hGFAP-promoter sequences led to cerebellar hypoplasia, inappropriate positioning of Bergmann glia cells in the molecular layer, undirected outgrowth of radial glia fibers, and granule cell ectopia. We therefore conclude that β1-integrin expression in cerebellar granule neurons is not essential during normal development or medulloblastoma formation. In fact, it is the expression of β1-integrin in glia that is crucial for the proper development of the cerebellar cortex.
authors.affiliation: Center for Neuropathology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Frick
authors.forename: Daniel
authors.initials: D
authors.lastname: Grammel
authors.forename: Felix
authors.initials: F
authors.lastname: Schmidt
authors.forename: Julia
authors.initials: J
authors.lastname: Pöschl
authors.forename: Markus
authors.initials: M
authors.lastname: Priller
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Pagella
authors.forename: André O
authors.initials: AO
authors.lastname: von Bueren
authors.forename: Aurelia
authors.initials: A
authors.lastname: Peraud
authors.forename: Jörg-Christian
authors.initials: JC
authors.lastname: Tonn
authors.forename: Jochen
authors.initials: J
authors.lastname: Herms
authors.forename: Stefan
authors.initials: S
authors.lastname: Rutkowski
authors.forename: Hans A
authors.initials: HA
authors.lastname: Kretzschmar
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schüller
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D002531:Cerebellum / Q000254:growth & development* / Q000276:immunology / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003594:Cytoplasmic Granules / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007223:Infant; D019012:Integrin beta1 / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009457:Neuroglia / Q000276:immunology / Q000378:metabolism*; D009474:Neurons / Q000276:immunology / Q000378:metabolism*; D055815:Young Adult
chemical_list: D019012:Integrin beta1