Homeostatic neurogenesis in the adult hippocampus does not involve amplification of Ascl1high intermediate progenitors

Lugert, Sebastian; Vogt, Miriam A.; Tchorz, Jan S.; Müller, Matthias; Giachino, Claudio; Taylor, Verdon

doi:10.1038/ncomms1670

Cited by 93 publications

(92 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NSCs in the DG of the adult mouse are Notch-dependent and express the Notch target Hes5 (Lugert et al, 2010(Lugert et al, , 2012. Drosha is expressed by most cells in the DG including GFAP + and Hes5 + radial NSCs ( Figure S1A and S1B).…”

Section: Drosha Deletion From Adult Dg Nscs Impairs Neurogenesismentioning

confidence: 99%

“…0.001 (**) 0.006 (**) 0.005 (**) 0.003 (**) (Chong et al, 2008;Harfe et al, 2005;Lugert et al, 2012;Tchorz et al, 2012). All mice were maintained on a C57BL6 background and were 8-10 weeks old at the onset of the experiments.…”

Section: Table S4 Related To Figure 4 and Figure S4mentioning

confidence: 99%

“…Drosha is expressed by most cells in the DG including GFAP + and Hes5 + radial NSCs ( Figure S1A and S1B). To address the functions of Drosha in neurogenic DG NSCs, we treated Hes5::CreER T2 mice carrying floxed Drosha (Drosha cKO) or wild type Drosha (ctrl) alleles with Tamoxifen (TAM), and followed cell fate by lineage tracing (Rosa26-CAG::EGFP) ( Figure 1A and S1A) (Lugert et al, 2012). Twenty-one days after TAM administration, Hes5 + NSCs and their progeny were Drosha-deficient and generated fewer cells compared to controls ( Figure S1B-D).…”

Section: Drosha Deletion From Adult Dg Nscs Impairs Neurogenesismentioning

confidence: 99%

See 2 more Smart Citations

Multipotency of Adult Hippocampal NSCs In Vivo Is Restricted by Drosha/NFIB

et al. 2016

Self Cite

View full text Add to dashboard Cite

SUMMARYMulti-lineage neuronal, astrocytic and oligodendrocytic potential is considered a neural stem cell (NSC) trait. However, hippocampal NSCs generate neurons and astrocytes but not oligodendrocytes in vivo and how this is regulated is unknown. Here we show that the RNAseIII Drosha is an intrinsic regulator of stem cell maintenance and differentiation in the adult mouse hippocampus. Inactivation of Drosha results in exhaustion of the NSC pool, premature arrest of neurogenesis, and induction of oligodendrocyte fate commitment. Drosha silences Nuclear Factor IB (NFIB) in hippocampal NSCs by targeting a double-stranded hairpin in the NFIB mRNA, thereby repressing its expression in a Dicer and miRNA-independent manner. We show that NFIB is required and sufficient for oligodendrocyte fate and knockdown of NFIB rescues neurogenesis by Drosha-deficient hippocampal NSCs. Our findings reveal a novel mechanism for stem cell maintenance and oligodendrocyte fate restriction in the adult hippocampus.3

show abstract

Section: Drosha Deletion From Adult Dg Nscs Impairs Neurogenesismentioning

confidence: 99%

Section: Table S4 Related To Figure 4 and Figure S4mentioning

confidence: 99%

Section: Drosha Deletion From Adult Dg Nscs Impairs Neurogenesismentioning

confidence: 99%

See 1 more Smart Citation

Multipotency of Adult Hippocampal NSCs In Vivo Is Restricted by Drosha/NFIB

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Using a Notch reporter line, in which cells with ongoing Notch/RBPJK are GFP labeled (Hes5::GFP), the authors found that NSCs of SGZ with Notch/RBPJK signaling are the most multipotent of the total progenitors. In basal conditions these NSCs are, for the large part quiescent, but can rapidly switch into a neurogenic mode in response to maximal activity or exercise (Lugert et al, 2010(Lugert et al, , 2012. This important study indicates that the regenerative potential of neuronal progenitors is responsive to increased synchronized activity.…”

Section: Notch In Postnatal Neurogenesismentioning

confidence: 92%

Notch signaling in the brain: In good and bad times

Albèri

Hoey

Brai

et al. 2013

Ageing Research Reviews

View full text Add to dashboard Cite

“…The production of new neurons in the adult hippocampus is a tightly orchestrated, multi-step process involving the maintenance, activation and proliferation of stem cells, differentiation and migration of intermediate progenitors, and maturation and integration of newborn neurons [25][26][27]. Under basal conditions, neural stem cells can either be in a resting, quiescent state, or they can be actively dividing [23,28,29].…”

Section: Adult Hippocampal Neurogenesismentioning

confidence: 99%

The role of the N-methyl-d-aspartate receptor in the proliferation of adult hippocampal neural stem and precursor cells

Taylor

Bartlett

2014

Sci. China Life Sci.

View full text Add to dashboard Cite

New neurons are continuously generated from resident pools of neural stem and precursor cells (NSPCs) in the adult brain. There are multiple pathways through which adult neurogenesis is regulated, and here we review the role of the N-methyl-D-aspartate receptor (NMDAR) in regulating the proliferation of NSPCs in the adult hippocampus. Hippocampal-dependent learning tasks, enriched environments, running, and activity-dependent synaptic plasticity, all potently up-regulate hippocampal NSPC proliferation. We first consider the requirement of the NMDAR in activity-dependent synaptic plasticity, and the role the induction of synaptic plasticity has in regulating NSPCs and newborn neurons. We address how specific NMDAR agonists and antagonists modulate proliferation, both in vivo and in vitro, and then review the evidence supporting the hypothesis that NMDARs are present on NSPCs. We believe it is important to understand the mechanisms underlying the activation of adult neurogenesis, given the potential that endogenous stem cell populations have for repopulating the hippocampus with functional new neurons. In conditions such as age-related memory decline, neurodegeneration and psychiatric disease, mature neurons are lost or become defective; as such, stimulating adult neurogenesis may provide a therapeutic strategy to overcome these conditions. The adult brain continuously generates new neurons throughout life. These adult-born neurons arise from endogenous neural stem and precursor cells (NSPCs), which primarily reside within two neurogenic niches: the subgranular zone (SGZ) in the dentate gyrus (DG) of the hippocampus, and the subventricular zone (SVZ) of the lateral ventricles. In the 20 years since adult mammalian neurogenesis started receiving substantial attention [1,2], scientists have made great progress in understanding the mechanisms that regulate stem cell maintenance, proliferation, differentiation, maturation and integration [3,4]. Early on, extrinsic cues from the environment, such as learning [5], physical activity [6], and enriched environments [7,8], were found to potently enhance hippocampal neurogenesis. It was not long before a link was made to synaptic plasticity [9], which is also enhanced by physical exercise [10], and is widely accepted as the synaptic mechanism underlying hippocampal learning and memory [11]. Synaptic plasticity and adult hippocampal neurogenesis are intimately linked, as long-term potentiation (LTP), an activity-dependent change in synaptic efficacy, can influence the activation and proliferation of NSPCs in the DG (e.g., [12]), as well as the survival of newborn neurons (e.g., [13]). These newborn neurons have biophysical characteris-

show abstract

Homeostatic neurogenesis in the adult hippocampus does not involve amplification of Ascl1high intermediate progenitors

Cited by 93 publications

References 59 publications

Multipotency of Adult Hippocampal NSCs In Vivo Is Restricted by Drosha/NFIB

Multipotency of Adult Hippocampal NSCs In Vivo Is Restricted by Drosha/NFIB

Notch signaling in the brain: In good and bad times

The role of the N-methyl-d-aspartate receptor in the proliferation of adult hippocampal neural stem and precursor cells

Contact Info

Product

Resources

About