Committed Neuronal Precursors Confer Astrocytic Potential on Residual Neural Precursor Cells
Committed Neuronal Precursors Confer Astrocytic Potential on Residual Neural Precursor Cells
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DOI：
10.1016/j.devcel.2008.12.014
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发表时间：
2009-02-17
影响因子：
11.8
通讯作者：
Nakashima, Kinichi
中科院分区：
文献类型：
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作者：
Namihira, Masakazu;Kohyama, Jun;Nakashima, Kinichi
在妊娠中期，哺乳动物神经前体细胞（NPC）仅分化为神经元。星形胶质细胞的生成在这个阶段被阻止，因为星形胶质细胞特异性基因启动子被甲基化。星形胶质细胞基因如何从抑制到表达的转换尚不清楚。我们在这项研究中表明，Notch配体表达在妊娠中期端脑的神经元前体和年轻神经元上，并且邻近的Notch激活的NPC获得成为星形胶质细胞的潜力。在妊娠中期NPC中Notch信号通路的激活诱导转录因子核因子1的表达，其结合星形胶质细胞基因启动子，导致星形胶质细胞特异性基因的去甲基化。这些发现为为什么神经元首先出现提供了一个机制解释：定向神经元前体和年轻神经元增强剩余的NPC分化成下一个细胞谱系，星形胶质细胞。
During midgestation, mammalian neural precursor cells (NPCs) differentiate only into neurons. Generation of astrocytes is prevented at this stage, because astrocyte-specific gene promoters are methylated. How the subsequent switch from suppression to expression of astrocytic genes occurs is unknown. We show in this study that Notch ligands are expressed on committed neuronal precursors and young neurons in mid-gestational telencephalon, and that neighboring Notch-activated NPCs acquire the potential to become astrocytes. Activation of the Notch signaling pathway in midgestational NPCs induces expression of the transcription factor nuclear factor 1, which binds to astrocytic gene promoters, resulting in demethylation of astrocyte-specific genes. These findings provide a mechanistic explanation for why neurons come first: committed neuronal precursors and young neurons potentiate remaining NPCs to differentiate into the next cell lineage, astrocytes.