title: Wnt-mediated activation of NeuroD1 and retro-elements during adult neurogenesis.
abstract: 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.
authors.affiliation: National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Science City, Japan. t.warashina@aist.go.jp
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kuwabara
authors.forename: Jenny
authors.initials: J
authors.lastname: Hsieh
authors.forename: Alysson
authors.initials: A
authors.lastname: Muotri
authors.forename: Gene
authors.initials: G
authors.lastname: Yeo
authors.forename: Masaki
authors.initials: M
authors.lastname: Warashina
authors.forename: Dieter Chichung
authors.initials: DC
authors.lastname: Lie
authors.forename: Lynne
authors.initials: L
authors.lastname: Moore
authors.forename: Kinichi
authors.initials: K
authors.lastname: Nakashima
authors.forename: Makoto
authors.initials: M
authors.lastname: Asashima
authors.forename: Fred H
authors.initials: FH
authors.lastname: Gage
mesh_terms: D053687:Adult Stem Cells / Q000502:physiology*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D006624:Hippocampus / Q000502:physiology*; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D051820:TCF Transcription Factors / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism*; D060508:Wnt3 Protein; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D055748:SOXB1 Transcription Factors; D051820:TCF Transcription Factors; D051153:Wnt Proteins; D060508:Wnt3 Protein; D051176:beta Catenin; C495267:CTNNB1 protein, mouse; C501008:Neurod1 protein, mouse; C527783:Sox2 protein, mouse
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