Nature Neuroscience
8, 873 - 880 (2005)
Published online: 19 June 2005; | doi:10.1038/nn1492
DNER acts as a neuron-specific Notch ligand during Bergmann glial developmentMototsugu Eiraku1, 2, 3, Akira Tohgo4, Katsuhiko Ono5, Megumi Kaneko1, Kazuto Fujishima1, 2, 3, Tomoo Hirano2, 3
& Mineko Kengaku1, 31
Laboratory for Neural Cell Polarity, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama
351-0198, Japan. 2
Department of Biophysics, Graduate School of Science, Kyoto University, Kyoto
606-8502, Japan. 3
CREST, Japan Science and Technology Corporation, Saitama
332-0012, Japan. 4
Department of Biochemistry, Tohoku University Graduate School of Medicine, Miyagi
980-8575, Japan. 5
Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, Myodaiji, Okazaki
444-8585, Japan.
Correspondence should be addressed to Mineko Kengaku kengaku@brain.riken.jpDifferentiation of CNS glia is regulated by Notch signaling through neuron-glia interaction. Here, we identified Delta/Notch-like EGF-related receptor (DNER), a neuron-specific transmembrane protein, as a previously unknown ligand of Notch during cellular morphogenesis of Bergmann glia in the mouse cerebellum. DNER binds to Notch1 at cell-cell contacts and activates Notch signaling in vitro. In the developing cerebellum, DNER is highly expressed in Purkinje cell dendrites, which are tightly associated with radial fibers of Bergmann glia expressing Notch. DNER specifically binds to Bergmann glia in culture and induces process extension by activating  -secretase− and Deltex-dependent Notch signaling. Inhibition of Deltex-dependent, but not RBP-J−dependent, Notch signaling in Bergmann glia suppresses formation and maturation of radial fibers in organotypic slice cultures. Additionally, deficiency of DNER retards the formation of radial fibers and results in abnormal arrangement of Bergmann glia. Thus, DNER mediates neuron-glia interaction and promotes morphological differentiation of Bergmann glia through Deltex-dependent Notch signaling.
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