OpenSSL SSL_connect: Connection reset by peer in connection to v2.sherpa.ac.uk:443 PuSH - Publication Server of Helmholtz Zentrum München: Wnt-mediated activation of NeuroD1 and retro-elements during adult neurogenesis.

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Kuwabara, T.* ; Hsieh, J.* ; Muotri, A.* ; Yeo, G.* ; Warashina, M.* ; Lie, D.C. ; Moore, L.* ; Nakashima, K.* ; Asashima, M.* ; Gage, F.H.*

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

Nat. Neurosci. 12, 1097-1105 (2009)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords 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
Journal Nature Neuroscience
Quellenangaben Volume: 12, Issue: 9, Pages: 1097-1105 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place NEW YORK
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Developmental Genetics (IDG)