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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Wnt-mediated activation of NeuroD1 and retro-elements during adult neurogenesis.
Nat. Neurosci. 12, 1097-1105 (2009)
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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
dentate gyrus; progenitor cells; beta-catenin; hippocampal neurogenesis; lentiviral vector; cerebral-cortex; granule cells; stem-cells; in-vivo; gene
ISSN (print) / ISBN
1097-6256
e-ISSN
1546-1726
Zeitschrift
Nature Neuroscience
Quellenangaben
Band: 12,
Heft: 9,
Seiten: 1097-1105
Verlag
Nature Publishing Group
Verlagsort
NEW YORK
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Developmental Genetics (IDG)