DNER acts as a neuron-specific Notch ligand during Bergmann glial development
DNER acts as a neuron-specific Notch ligand during Bergmann glial development
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DOI：
10.1038/nn1492
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发表时间：
2005-07-01
影响因子：
25
通讯作者：
Kengaku, M
中科院分区：
文献类型：
--
作者：
Eiraku, M;Tohgo, A;Kengaku, M
神经胶质细胞分化受神经元-神经胶质细胞相互作用的Notch信号调控。在这里，我们鉴定了Delta/Notch样EGF相关受体(DNER)，一种神经元特异性跨膜蛋白，在小鼠小脑Bergmann胶质细胞的细胞形态发生过程中，是一个未知的Notch配体。在体外，DNER与Notch1结合并激活Notch信号。在发育中的小脑中，DNER在浦肯野细胞树突中高表达，这些树突与表达Notch的Bergmann神经胶质纤维密切相关。DNER在培养中与Bergmann胶质细胞特异性结合，并通过激活γ-分泌酶和Deltex依赖的Notch信号来诱导突起延伸。Bergmann胶质细胞中依赖Deltex而不依赖RBP-J的Notch信号的抑制抑制了器官型切片培养中放射状纤维的形成和成熟。此外，DNER的缺乏阻碍了放射状纤维的形成，导致Bergmann胶质细胞排列异常。因此，DNER通过Deltex依赖的Notch信号介导神经元与胶质细胞的相互作用，促进Bergmann胶质细胞的形态分化。
Differentiation 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 gamma-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.