title: Impaired cerebellar functions in mutant mice lacking DNER.
abstract: DNER is a transmembrane protein carrying extracellular EGF repeats and is strongly expressed in Purkinje cells (PCs) in the cerebellum. Current study indicated that DNER functions as a new Notch ligand and mediates the functional communication via cell-cell interaction. By producing and analyzing knockout mice lacking DNER, we demonstrate its essential roles in functional and morphological maturation of the cerebellum. The knockout mice exhibited motor discoordination in the fixed bar and rota-rod tests. The cerebellum from the knockout mice showed significant retardation in morphogenesis and persistent abnormality in fissure organization. Histochemical and electrophysiological analyses detected that PCs retained multiple innervations from climbing fibers (CFs) in the mutant cerebellum. Synaptic transmission from parallel fibers (PFs) or CFs to PCs was apparently normal, while glutamate clearance at the PF-PC synapses was significantly impaired in the mutant mice. Moreover, the protein level of GLAST, the glutamate transporter predominantly expressed in Bergmann glia (BG), was reduced in the mutant cerebellum. Our results indicate that DNER takes part in stimulation of BG maturation via intercellular communication and is essential for precise cerebellar development.
authors.affiliation: Department of Medical Chemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Tohgo
authors.forename: Mototsugu
authors.initials: M
authors.lastname: Eiraku
authors.forename: Taisuke
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Eriko
authors.initials: E
authors.lastname: Miura
authors.forename: Shin-Ya
authors.initials: SY
authors.lastname: Kawaguchi
authors.forename: Miyuki
authors.initials: M
authors.lastname: Nishi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Tomoo
authors.initials: T
authors.lastname: Hirano
authors.forename: Mineko
authors.initials: M
authors.lastname: Kengaku
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeshima
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002531:Cerebellum / Q000033:anatomy & histology / Q000254:growth & development / Q000502:physiology* / Q000503:physiopathology*; D018698:Glutamic Acid / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: C486765:Dner protein, mouse; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D018698:Glutamic Acid