title: A role for Bicaudal-D2 in radial cerebellar granule cell migration.
abstract: Bicaudal-D (BICD) belongs to an evolutionary conserved family of dynein adaptor proteins. It was first described in Drosophila as an essential factor in fly oogenesis and embryogenesis. Missense mutations in a human BICD homologue, BICD2, have been linked to a dominant mild early onset form of spinal muscular atrophy. Here we further examine the in vivo function of BICD2 in Bicd2 knockout mice. BICD2-deficient mice develop disrupted laminar organization of cerebral cortex and the cerebellum, pointing to impaired radial neuronal migration. Using astrocyte and granule cell specific inactivation of BICD2, we show that the cerebellar migration defect is entirely dependent upon BICD2 expression in Bergmann glia cells. Proteomics analysis reveals that Bicd2 mutant mice have an altered composition of extracellular matrix proteins produced by glia cells. These findings demonstrate an essential non-cell-autonomous role of BICD2 in neuronal cell migration, which might be connected to cargo trafficking pathways in glia cells.
authors.affiliation: 1] Erasmus Medical Center, Department of Neuroscience, 3015 GE Rotterdam, The Netherlands [2].
authors.forename: Dick
authors.initials: D
authors.lastname: Jaarsma
authors.affiliation: 1] Erasmus Medical Center, Department of Neuroscience, 3015 GE Rotterdam, The Netherlands [2] Cell Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands [3].
authors.forename: Robert
authors.initials: R
authors.lastname: van den Berg
authors.affiliation: 1] Erasmus Medical Center, Department of Neuroscience, 3015 GE Rotterdam, The Netherlands [2] Cell Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands [3].
authors.forename: Phebe S
authors.initials: PS
authors.lastname: Wulf
authors.affiliation: Netherlands Institute for Neuroscience, Royal Dutch Academy of Arts & Sciences, 1105 BA Amsterdam, The Netherlands.
authors.forename: Susan
authors.initials: S
authors.lastname: van Erp
authors.affiliation: Erasmus Medical Center, Department of Neuroscience, 3015 GE Rotterdam, The Netherlands.
authors.forename: Nanda
authors.initials: N
authors.lastname: Keijzer
authors.affiliation: Erasmus Medical Center, Department of Neuroscience, 3015 GE Rotterdam, The Netherlands.
authors.forename: Max A
authors.initials: MA
authors.lastname: Schlager
authors.affiliation: 1] Erasmus Medical Center, Department of Neuroscience, 3015 GE Rotterdam, The Netherlands [2] Cell Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: de Graaff
authors.affiliation: 1] Erasmus Medical Center, Department of Neuroscience, 3015 GE Rotterdam, The Netherlands [2] Netherlands Institute for Neuroscience, Royal Dutch Academy of Arts & Sciences, 1105 BA Amsterdam, The Netherlands.
authors.forename: Chris I
authors.initials: CI
authors.lastname: De Zeeuw
authors.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands.
authors.forename: R Jeroen
authors.initials: RJ
authors.lastname: Pasterkamp
authors.affiliation: 1] Cell Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands [2] Department of Cell Biology, Erasmus Medical Center, 3015 GE Rotterdam, The Netherlands.
authors.forename: Anna
authors.initials: A
authors.lastname: Akhmanova
authors.affiliation: 1] Erasmus Medical Center, Department of Neuroscience, 3015 GE Rotterdam, The Netherlands [2] Cell Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands.
authors.forename: Casper C
authors.initials: CC
authors.lastname: Hoogenraad
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D002465:Cell Movement; D002531:Cerebellum / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D013997:Time Factors
chemical_list: C435206:Bicd2 protein, mouse; D008869:Microtubule-Associated Proteins