Notch Activity Levels Control the Balance between Quiescence and Recruitment of Adult Neural Stem Cells

Chapouton, Prisca; Skupien, Paulina; Hesl, Birgit; Coolen, Marion; Moore, John C.; Madelaine, Romain; Kremmer, E.; Faus-Keßler, Theresa; Blader, Patrick; Lawson, Nathan D.; Bally‐Cuif, Laure

doi:10.1523/jneurosci.6170-09.2010

Cited by 238 publications

(277 citation statements)

References 68 publications

Supporting

Mentioning

264

Contrasting

Unclassified

Order By: Relevance

“…This is similar to the role of Notch during constitutive neurogenesis in the forebrain of zebrafish (Chapouton et al, 2010;Rothenaigner et al, 2011) and is compatible with a role of Notch signaling in maintaining progenitor pools. Remarkably, the function of Notch in the regenerating spinal cord of zebrafish is similar to its proposed role in the lesioned spinal cord of rats, where Notch is strongly upregulated and acts as an anti-neurogenic factor in vitro (Yamamoto et al, 2001).…”

Section: Discussionsupporting

confidence: 81%

“…Even when the active form of Notch was overexpressed, leading to increased her4.1 expression in the ependymal zone, proliferation and motor neuron generation were not influenced. This contrasts with progenitor zones in the adult brain of zebrafish and mice that show constant activity of Notch signaling (Carlén et al, 2009;Chapouton et al, 2010). These observations suggest that ependymo-radial glial cells in the adult zebrafish spinal cord need unknown signals from the lesion event that switch on Notch signaling and neurogenesis (Reimer et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…The gamma-secretase inhibitor DAPT prevents cleavage of the Notch receptor into its active form and has been shown to attenuate Notch signaling in adult zebrafish (Chapouton et al, 2010). Indeed a single intraperitoneal injection at 4 dpl was sufficient to reduce detectability of her4.1 in PCRs of lesioned spinal tissue at 5 dpl (Fig.…”

Section: Dapt Treatment Increases the Number Of Newly Generated Motormentioning

confidence: 96%

See 2 more Smart Citations

Notch Signaling Controls Generation of Motor Neurons in the Lesioned Spinal Cord of Adult Zebrafish

Dias¹,

Yang²,

Ogai³

et al. 2012

J. Neurosci.

View full text Add to dashboard Cite

In mammals, increased Notch signaling is held partly responsible for a lack of neurogenesis after a spinal injury. However, this is difficult to test in an essentially nonregenerating system. We show that in adult zebrafish, which exhibit lesion-induced neurogenesis, e.g., of motor neurons, the Notch pathway is also reactivated. Although apparently compatible with neuronal regeneration in zebrafish, forced activity of the pathway significantly decreased progenitor proliferation and motor neuron generation. Conversely, pharmacological inhibition of the pathway increased proliferation and motor neuron numbers. This demonstrates that Notch is a negative signal for regenerative neurogenesis, and, importantly, that spinal motor neuron regeneration can be augmented in an adult vertebrate by inhibiting Notch signaling.

show abstract

Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Dapt Treatment Increases the Number Of Newly Generated Motormentioning

confidence: 96%

See 1 more Smart Citation

Notch Signaling Controls Generation of Motor Neurons in the Lesioned Spinal Cord of Adult Zebrafish

Dias¹,

Yang²,

Ogai³

et al. 2012

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Although Notch1 is expressed by quiescent (PCNA Ϫ ) NSCs, we do not have evidence for prococious differentiation of qNSCs or their entry into mitosis in its absence, unlike following the loss of RBP-J. A possible explanation for the differences in pheonotype between Notch1 and RBP-J cKO mice is that other members of the Notch family may induce the signals through RBP-J that repress proliferation in qNSCs (Chapouton et al, 2010). Alternatively, other Notch family members could functionally compensate the Notch1 deletion.…”

Section: Notch1 Regulates Homeostatic Neurogenesis In the Adult Forebmentioning

confidence: 58%

Neurogenic Subventricular Zone Stem/Progenitor Cells Are Notch1-Dependent in Their Active But Not Quiescent State

Basak

Giachino²,

Fiorini³

et al. 2012

J. Neurosci.

149

147

View full text Add to dashboard Cite

The adult mammalian forebrain contains neural stem/progenitor cells (NSCs) that generate neurons throughout life. As in other somatic stem cell systems, NSCs are proposed to be predominantly quiescent and proliferate only sporadically to produce more committed progeny. However, quiescence has recently been shown not to be an essential criterion for stem cells. It is not known whether NSCs show differences in molecular dependence based on their proliferation state. The subventricular zone (SVZ) of the adult mouse brain has a remarkable capacity for repair by activation of NSCs. The molecular interplay controlling adult NSCs during neurogenesis or regeneration is not clear but resolving these interactions is critical in order to understand brain homeostasis and repair. Using conditional genetics and fate mapping, we show that Notch signaling is essential for neurogenesis in the SVZ. By mosaic analysis, we uncovered a surprising difference in Notch dependence between active neurogenic and regenerative NSCs. While both active and regenerative NSCs depend upon canonical Notch signaling, Notch1-deletion results in a selective loss of active NSCs (aNSCs). In sharp contrast, quiescent NSCs (qNSCs) remain after Notch1 ablation until induced during regeneration or aging, whereupon they become Notch1-dependent and fail to fully reinstate neurogenesis. Our results suggest that Notch1 is a key component of the adult SVZ niche, promoting maintenance of aNSCs, and that this function is compensated in qNSCs. Therefore, we confirm the importance of Notch signaling for maintaining NSCs and neurogenesis in the adult SVZ and reveal that NSCs display a selective reliance on Notch1 that may be dictated by mitotic state.

show abstract

“…Furthermore, in the constitutive neurogenic niche of the SVZ, the cell cycle of GFAP + cells is under tonic GABA control, which is released from the maturing neuroblasts (Liu et al, 2005;Fernando et al, 2011). Interestingly, work in the zebrafish telencephalon identified a self-limiting mechanism that controls continuous neurogenesis through inter-progenitor cell communication, in a process by which cycling progenitors inhibit the cell cycle progression of their neighbors (Chapouton et al, 2010). Although the regulation described in zebrafish relies on lateral inhibition mediated by Notch signaling rather than any neurotransmitter-mediated activity, these observations further indicate the existence of feedback loops during neurogenesis in several contexts and species.…”

Section: Neurotransmitter-mediated Control Of Quiescencementioning

confidence: 99%

Neurotransmitter-mediated control of neurogenesis in the adult vertebrate brain

et al. 2013

View full text Add to dashboard Cite

SummaryIt was long thought that no new neurons are added to the adult brain. Similarly, neurotransmitter signaling was primarily associated with communication between differentiated neurons. Both of these ideas have been challenged, and a crosstalk between neurogenesis and neurotransmitter signaling is beginning to emerge. In this Review, we discuss neurotransmitter signaling as it functions at the intersection of stem cell research and regenerative medicine, exploring how it may regulate the formation of new functional neurons and outlining interactions with other signaling pathways. We consider evolutionary and cross-species comparative aspects, and integrate available results in the context of normal physiological versus pathological conditions. We also discuss the potential role of neurotransmitters in brain size regulation and implications for cell replacement therapies. Key words: Adult neurogenesis, Homeostasis, Neural stem cell, Neurotransmitter, Regeneration IntroductionIn the brain, signaling via neurotransmitters, small molecules released by neurons to communicate with other cells, has primarily been associated with the function rather than with the formation of neurons. However, several reports have identified roles for neurotransmitters in cell fate determination in a wide range of species both within and outside the central nervous system (CNS). A thorough discussion on the evolutionary origin of neurotransmitter signaling is outside the scope of this Review, but it is important to note that both neurotransmitters and their receptors (see Table 1) are present and functionally important in organisms without a nervous system. For example, γ-aminobutyric acid (GABA), glutamate and nitric oxide (NO) have all been detected in sponges and shown to regulate cell behavior (Ellwanger et al., 2007;Elliott and Leys, 2010). A recent transcriptome profiling of the sponge A. queenslandica revealed the expression of wide repertoire of components active in synapses found in the vertebrate nervous systems (Conaco et al., 2012). In the social amoeba Dictysotelium, disruption of a glutamate receptor by homologous recombination reveals a role for glutamate signaling in the suppression of cell division (Taniura et al., 2006), while GABA induces terminal differentiation of spores through a GABA B receptor (Anjard and Loomis, 2006). GABA and glutamate appear to play opposing roles in spore induction (Fountain, 2010) in Dictyostelium, indicating that the apparent antagonistic relationship between glutamate and GABA signaling was established prior to the evolution of synaptic communication in the CNS.Furthermore, neurotransmitters control cell proliferation during development long before the onset of neurogenesis in mammals, as exemplified by GABA signaling in the early embryo (Andäng et al., 2008). Once developmental neurogenesis is initiated, neurotransmitter signaling has an impact on several aspects of neurogenesis, including proliferation, migration and differentiation in various locations in the CNS, such as the tele...

show abstract

Notch Activity Levels Control the Balance between Quiescence and Recruitment of Adult Neural Stem Cells

Cited by 238 publications

References 68 publications

Notch Signaling Controls Generation of Motor Neurons in the Lesioned Spinal Cord of Adult Zebrafish

Notch Signaling Controls Generation of Motor Neurons in the Lesioned Spinal Cord of Adult Zebrafish

Neurogenic Subventricular Zone Stem/Progenitor Cells Are Notch1-Dependent in Their Active But Not Quiescent State

Neurotransmitter-mediated control of neurogenesis in the adult vertebrate brain

Contact Info

Product

Resources

About