RBP-J promotes neuronal differentiation and inhibits oligodendroglial development in adult neurogenesis
RBP-J promotes neuronal differentiation and inhibits oligodendroglial development in adult neurogenesis
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DOI：
10.1016/j.ydbio.2009.06.001
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发表时间：
2009-08-15
影响因子：
2.7
通讯作者：
Tanigaki, Kenji
中科院分区：
文献类型：
--
作者：
Fujimoto, Motoaki;Takagi, Yasushi;Tanigaki, Kenji
神经发生持续存在于成年脊椎动物大脑的限制区域。然而，支持成人神经发生的分子机制尚未完全了解。在这里，我们证明了在成年脑室下区（SVZ）中的C细胞特异性缺失RBP-J导致嗅球（OB）中成熟颗粒细胞数量减少，同时Olig 2（+）少突胶质祖细胞数量增加，尽管SVZ中未成熟神经元的生成增加。将腺病毒介导的Cre导入RBP-J-floxed小鼠的SVZ中表明，OB中的Olig 2（+）细胞可以从RBP-J-缺陷的SVZ中产生，尽管OB中的少突胶质细胞不来源于正常SVZ。这种向少突胶质祖细胞的优先分化和成熟神经元分化的减少也通过体外培养RBP-J缺陷SVZ衍生的神经祖细胞证实，除了在维持成体神经干细胞群体中的缺陷。在RBP-J缺陷的神经元的成熟缺陷，可以部分挽救敲低Olig 2在体内。我们的研究结果表明，RBP-J可能至少部分通过Olig 2的转录抑制来调节神经元的成熟。(C)2009 Elsevier Inc. All rights reserved.
Neurogenesis persists in restricted regions of the adult vertebrate brain. However, the molecular mechanisms supporting adult neurogenesis are not fully understood. Here we demonstrated that C cell-specific deletion of RBP-J in the adult subventricular zones (SVZs) caused reduction in numbers of mature granule cells in the olfactory bulbs (OBs) with concomitant increase in Olig2(+) oligodendroglial progenitors, although generation of immature neurons was enhanced in the SVZs. Adenovirus-mediated Cre introduction to the SVZs of RBP-J-floxed mice indicated that Olig2(+) cells in the OBs can be generated from RBP-J-deficient SVZs, although no oligodendroglial cells in the OBs are derived from the normal SVZs. This preferential differentiation to oligodendroglial progenitor cells and reduction in differentiation of mature neurons were also confirmed by in vitro culture of RBP-J-deficient SVZ-derived neural progenitor cells, in addition to defects in the maintenance of adult neural stern cell population. The defects in maturation of RBP-J-deficient neurons could be partly rescued by knockdown of Olig2 in vivo. Our findings suggest that RBP-J might regulate neuronal maturation at least in part through transcriptional repression of Olig2. (C) 2009 Elsevier Inc. All rights reserved.