NB-3/Notch1 pathway via Deltex1 promotes neural progenitor cell differentiation into oligodendrocytes
NB-3/Notch1 pathway via Deltex1 promotes neural progenitor cell differentiation into oligodendrocytes
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DOI：
10.1074/jbc.m313505200
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发表时间：
2004-06-11
影响因子：
4.8
通讯作者：
Xiao, ZC
中科院分区：
文献类型：
--
作者：
Cui, XY;Hu, QD;Xiao, ZC
脊椎动物中枢神经系统中的神经元和神经胶质细胞在时间上是不同的，尽管是重叠的。神经元首先从普通祖细胞产生，然后是星形胶质细胞和少突胶质细胞。越来越多的证据表明，轴突来源的信号在时空上调节少突胶质细胞的成熟和髓鞘的形成。我们先前的观察表明，在少突胶质细胞成熟过程中，F3/Conactin是Notch的一个功能配体，揭示了另一组Notch配体的存在。在这里，我们确定了Nb-3，F3/Conactin家族的成员，作为一种新的Notch配体参与了少突胶质细胞的生成。NB-3触发Notch胞内域的核移位，并通过Deltex 1促进祖细胞的少突胶质形成和少突胶质前体细胞的分化。在原代少突胶质细胞中，NB-3增加髓鞘相关糖蛋白转录本。因此，NB-3/Notch信号通路可能被证明是治疗脱髓鞘疾病的分子手柄。
Neurons and glia in the vertebrate central nervous system arise in temporally distinct, albeit overlapping, phases. Neurons are generated first followed by astrocytes and oligodendrocytes from common progenitor cells. Increasing evidence indicates that axon-derived signals spatiotemporally modulate oligodendrocyte maturation and myelin formation. Our previous observations demonstrate that F3/contactin is a functional ligand of Notch during oligodendrocyte maturation, revealing the existence of another group of Notch ligands. Here, we establish that NB-3, a member of the F3/contactin family, acts as a novel Notch ligand to participate in oligodendrocyte generation. NB-3 triggers nuclear translocation of the Notch intracellular domain and promotes oligodendrogliogenesis from progenitor cells and differentiation of oligodendrocyte precursor cells via Deltex1. In primary oligodendrocytes, NB-3 increases myelin-associated glycoprotein transcripts. Thus, the NB-3/Notch signaling pathway may prove to be a molecular handle to treat demyelinating diseases.