Wnt-mediated activation of NeuroD1 and retro-elements during adult neurogenesis

Tomoko Kuwabara, Jenny Hsieh, Alysson Muotri, Gene Yeo, Masaki Warashina, Dieter Chichung Lie, Lynne Moore, Kinichi Nakashima, Makoto Asashima, Fred H. Gage

研究成果: Contribution to journalArticle査読

424 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)1097-1105
ページ数9
ジャーナルNature Neuroscience
12
9
DOI
出版ステータス出版済み - 9 2009
外部発表はい

All Science Journal Classification (ASJC) codes

  • 神経科学(全般)

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