Notch and MAML Signaling Drives Scl-Dependent Interneuron Diversity in the Spinal Cord

Peng, Chian Yu; Yajima, Hiroshi; Burns, Caroline E.; Zon, Leonard I.; Sisodia, Sangram S.; Pfaff, Samuel L.; Sharma, Kamal

doi:10.1016/j.neuron.2007.02.019

Cited by 165 publications

(240 citation statements)

References 57 publications

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“…Notch function is implicated in binary fate choice in many developing systems. In the CNS alone, this is the case for selecting between spinal cord interneuron subtypes (Peng et al, 2007), interneurons/motoneurons (Shin et al, 2007), motoneurons/oligodendrocytes (Park and Appel, 2003), habenular subnuclei (Aizawa et al, 2007), epiphysis photoreceptors/projection neurons (Cau et al, 2008), pituitary secretory cell types (Zhu et al, 2006), or between retinal neuronal subtypes and Mueller glia (Scheer et al, 2001;Bernardos et al, 2005;Jadhav et al, 2006). These fate choices often implicate the maintenance by Notch of a progenitor state as opposed to differentiation, and such a mechanism fits with our results.…”

Section: Distinct Outcomes Of Notch Activitysupporting

confidence: 80%

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

Chapouton¹,

Skupien

Hesl

et al. 2010

Journal of Neuroscience

240

269

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The limited generation of neurons during adulthood is controlled by a balance between quiescence and recruitment of neural stem cells (NSCs). We use here the germinal zone of the zebrafish adult telencephalon to examine how the frequency of NSC divisions is regulated. We show, using several in vivo techniques, that progenitors transit back and forth between the quiescent and dividing state, according to varying levels of Notch activity: Notch induction drives progenitors into quiescence, whereas blocking Notch massively reinitiates NSC division and subsequent commitment toward becoming neurons. Notch activation appears predominantly triggered by newly recruited progenitors onto their neighbors, suggesting an involvement of Notch in a self-limiting mechanism, once neurogenesis is started. These results identify for the first time a lateral inhibition-like mechanism in the context of adult neurogenesis and suggest that the equilibrium between quiescence and neurogenesis in the adult brain is controlled by fluctuations of Notch activity, thereby regulating the amount of adult-born neurons.

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Section: Distinct Outcomes Of Notch Activitysupporting

confidence: 80%

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

Chapouton¹,

Skupien

Hesl

et al. 2010

Journal of Neuroscience

240

269

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“…It is hypothesized that the long duration or high intensity of Notch activity imposes irreversible changes in gene expression and/or epigenetic status and thus enables progenitor cells competent to adopt an alternative cell fate [22]. This is consistent with recent findings of Notch function in other developmental contexts [25][26][27][28]. Interestingly, it has been shown recently that the conserved first intron region of the Prop1 gene is capable of conferring dorsal expression of a transgene driven by a heterologous promoter, suggesting that this element is critical for the spatial expression of endogenous Prop1 during pituitary development.…”

Section: Temporally Regulated Notch Signaling Is Required For Sequentsupporting

confidence: 86%

Signaling and epigenetic regulation of pituitary development

Zhu

Wang

et al. 2007

Current Opinion in Cell Biology

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The developing pituitary gland provides an instructive model system for elucidating the molecular mechanisms by which distinct cell types arise from a common progenitor lineage accompanied by changes in the chromatin status in response to multiple extrinsic and intrinsic signals. Recent studies have shed light on the integration between signaling molecules and activation of transcription factors that are essential for cell fate commitment and terminal differentiation. Investigation of the in vivo function of the histone modifying enzyme LSD1 has revealed a new layer of regulatory mechanism in pituitary organogenesis. Epigenetic studies of the transcriptional events in terminal differentiation process have provided insights into the functions of non-coding RNA and developmentally regulated chromatin organization.

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“…This mechanism appears to be used by other CNS progenitors to generate neuronal diversity as well. For instance, during spinal cord development, Dll4 acts downstream of Foxn4 to specify the V2b inhibitory interneurons vs. the V2a excitatory interneurons (49,50), whereas Dll1 is required mainly for progenitor maintenance in the V2 domain (48).…”

Section: Dll4 Instead Of Dll1 Mediates Notch Signaling To Suppressmentioning

confidence: 99%

Forkhead box N4 (Foxn4) activates Dll4-Notch signaling to suppress photoreceptor cell fates of early retinal progenitors

Luo¹,

Jin²,

Xie³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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The generation of diverse neuronal types and subtypes from multipotent progenitors during development is crucial for assembling functional neural circuits in the adult central nervous system. During mouse retinogenesis, early retinal progenitors give rise to several cell types, including ganglion, amacrine, horizontal, cone, and rod cells. It is unknown at present how each of these fates is selected from the multiple neuronal fates available to the early progenitor. By using a combination of bioinformatic, genetic, and biochemical approaches, we investigated the mechanism by which Foxn4 selects the amacrine and horizontal cell fates from multipotential retinal progenitors. These studies indicate that Foxn4 has an intrinsic activity to suppress the alternative photoreceptor cell fates of early retinal progenitors by selectively activating Dll4-Notch signaling. Gene expression and conditional ablation analyses reveal that Dll4 is directly activated by Foxn4 via phylogenetically conserved enhancers and that Dll4 can partly mediate the Foxn4 function by serving as a major Notch ligand to expand the progenitor pool and limit photoreceptor production. Our data together define a Foxn4-mediated molecular and signaling pathway that underlies the suppression of alternative cell fates of early retinal progenitors.

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Notch and MAML Signaling Drives Scl-Dependent Interneuron Diversity in the Spinal Cord

Cited by 165 publications

References 57 publications

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

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

Signaling and epigenetic regulation of pituitary development

Forkhead box N4 (Foxn4) activates Dll4-Notch signaling to suppress photoreceptor cell fates of early retinal progenitors

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