2009
DOI: 10.1038/nn.2360
|View full text |Cite
|
Sign up to set email alerts
|

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 lo… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
1
1
1
1

Citation Types

22
560
2
3

Year Published

2011
2011
2019
2019

Publication Types

Select...
5
4

Relationship

0
9

Authors

Journals

citations
Cited by 569 publications
(587 citation statements)
references
References 42 publications
22
560
2
3
Order By: Relevance
“…[60] and the present study) and (b) there is no overlap between the expression of Sox2 and Neurod1 in the DG (refs. [61,62] and our unpublished observations), the lower LI of Neurod1 þ cells when compared with Neurod1 À cells suggests that immature actively proliferating precursors (type 2a) cycle more rapidly than do neuronally committed precursors (types 2b and 3), supporting for the first time the ''cell cycle length hypothesis'' for adult neurogenic niches. Moreover, the lengthening of G 1 observed in the absence of (F-I).…”
Section: Discussionsupporting
confidence: 55%
“…[60] and the present study) and (b) there is no overlap between the expression of Sox2 and Neurod1 in the DG (refs. [61,62] and our unpublished observations), the lower LI of Neurod1 þ cells when compared with Neurod1 À cells suggests that immature actively proliferating precursors (type 2a) cycle more rapidly than do neuronally committed precursors (types 2b and 3), supporting for the first time the ''cell cycle length hypothesis'' for adult neurogenic niches. Moreover, the lengthening of G 1 observed in the absence of (F-I).…”
Section: Discussionsupporting
confidence: 55%
“…A major finding in brain samples of Fmr1 -/-mice is the abnormally high levels of GSK3b, a key kinase shown to play critical roles in several molecular pathways, including MAPK, Cyclin, Akt, and the canonical Wnt/b-catenin signaling pathway [26,[45][46][47]. The role of GSK3b, as part of the canonical Wnt/bcatenin signaling pathway, was shown to be important during adult neurogenesis in the murine hippocampus [29] and in FXS pathology in Fmr1 -/-mice [27,28]. Ablation of FMRP in aNSCs leads to an increase in GSK3b protein levels, causing a phosphorylation-dependent decrease in bcatenin activation and an increase in b-catenin degradation, impairing neuronal differentiation.…”
Section: Expression Of Gsk3b and B-catenin In Fx-hnpcsmentioning
confidence: 99%
“…Studies conducted on Fmr1 -/-mice have consistently shown that lack of FMRP results in an abnormal increase in glycogen synthase kinase 3b (GSK3b) mRNA and protein levels [26]. Although GSK3b plays key roles in several molecular pathways, it has been proposed that its involvement in FXS neuropathology is mediated through the canonical Wnt/b-catenin signaling pathway [27,28], a critical signaling pathway for embryonic neural development as well as for adult neurogenesis [29]. These studies showed that ablation of FMRP in vivo reduced the capacity of murine adult neural stem cells (aNSCs) to differentiate into hippocampal neurons because of an increase in GSK3b and a consequent reduction in b-catenin and its downstream neuronal transcription factors, reducing neuronal yield and increasing the relative number of glia cells in the hippocampus.…”
Section: Introductionmentioning
confidence: 99%
“…There, β-catenin acts as a transcriptional coactivator of TCF/LEF transcription factors, resulting in the expression of Wnt target genes. Recently, it has been shown that NeuroD1, a basic helix-loop-helix transcription factor required for granule cell genesis in the embryonic and adult DG, is regulated by β-catenin-dependent signaling (9)(10)(11)(12). However, NeuroD1 is not only important for hippocampal neurogenesis but is also involved in the generation of SVZ-derived olfactory neurons (11,13,14).…”
mentioning
confidence: 99%