Wnt-mediated activation of NeuroD1 and retro-elements during adult neurogenesis.
Wnt-mediated activation of NeuroD1 and retro-elements during adult neurogenesis.
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DOI：
10.1038/nn.2360
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发表时间：
2009-09
影响因子：
25
通讯作者：
Gage, Fred H.
中科院分区：
文献类型：
--
作者：
Kuwabara, Tomoko;Hsieh, Jenny;Muotri, Alysson;Yeo, Gene;Warashina, Masaki;Lie, Dieter Chichung;Moore, Lynne;Nakashima, Kinichi;Asashima, Makoto;Gage, Fred H.
在成年海马中，神经干细胞（NSCs）不断产生新的神经元，但调控成年神经发生的分子机制仍然不清楚。我们发现，Wnt信号传导，连同Sox 2的去除，触发了小鼠中NeuroD 1的表达。这种转录调控机制依赖于启动子中含有重叠Sox 2和T细胞因子/淋巴增强因子（TCF/LEF）结合位点（Sox/LEF）的DNA元件。值得注意的是，Sox/LEF位点也发现在长散置核元件1（LINE-1）的元素，与它们的关键作用，在神经干细胞的过渡增殖神经元祖细胞。我们的研究结果描述了一种以前未知的Wnt介导的调节机制，该机制同时协调NeuroD 1和LINE-1的激活，这对成年神经发生和神经元祖细胞的存活很重要。此外，发现LINE-1逆转录元件嵌入在哺乳动物基因组中，可以作为双向启动子的功能表明，Sox/LEF调节位点可能代表一种一般机制，至少部分，中继环境信号到其他附近的基因座，以促进成年海马神经发生。
In adult hippocampus, new neurons are continuously generated from neural stem cells (NSCs), but the molecular mechanisms regulating adult neurogenesis remain elusive. We found that Wnt signaling, together with the removal of Sox2, triggered the expression of NeuroD1 in mice. This transcriptional regulatory mechanism was dependent on a DNA element containing overlapping Sox2 and T-cell factor/lymphoid enhancer factor (TCF/LEF)-binding sites (Sox/LEF) in the promoter. Notably, Sox/LEF sites were also found in long interspersed nuclear element 1 (LINE-1) elements, consistent with their critical roles in the transition of NSCs to proliferating neuronal progenitors. Our results describe a previously unknown Wnt-mediated regulatory mechanism that simultaneously coordinates activation of NeuroD1 and LINE-1, which is important for adult neurogenesis and survival of neuronal progenitors. Moreover, the discovery that LINE-1 retro-elements embedded in the mammalian genome can function as bi-directional promoters suggests that Sox/LEF regulatory sites may represent a general mechanism, at least in part, for relaying environmental signals to other nearby loci to promote adult hippocampal neurogenesis.
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影响因子：
2.7
作者：
Bani-Yaghoub, Mahmud;Tremblay, Roger G.;Sikorska, Marianna
通讯作者：
Sikorska, Marianna
影响因子：
2
作者：
Jessberger, Sebastian;Clark, Robert E.;Gage, Fred H.
通讯作者：
Gage, Fred H.
DOI：
10.1073/pnas.0407643101
发表时间：
2004-11-23
影响因子：
11.1
作者：
Hsieh, J;Nakashima, K;Gage, FH
通讯作者：
Gage, FH
影响因子：
10.5
作者：
Avilion, AA;Nicolis, SK;Lovell-Badge, R
通讯作者：
Lovell-Badge, R
影响因子：
25
作者：
Bylund, M;Andersson, E;Muhr, J
通讯作者：
Muhr, J