Fbw7 controls neural stem cell differentiation and progenitor apoptosis via Notch and c-Jun.

Abstract:

:Neural stem and progenitor cells (NSCs/NPCs) give rise to neurons, astrocytes and oligodendrocytes. However, the mechanisms underlying the decision of a stem cell to either self-renew or differentiate are incompletely understood. We demonstrate here that Fbw7 (F-box and WD repeat domain containing-7), the substrate recognition component of an SCF (complex of SKP1, CUL1 and F-box protein)-type E3 ubiquitin ligase, is a key regulator of NSC/NPC viability and differentiation. The absence of Fbw7 in the mouse brain caused severely impaired stem cell differentiation and increased progenitor cell death. Fbw7 deficiency resulted in accumulation of two SCF(Fbw7) substrates, the transcription factors active Notch1 and N-terminally phosphorylated c-Jun. Genetic and pharmacological rescue experiments identified c-Jun as a key substrate of Fbw7 in controlling progenitor cell viability, whereas inhibition of Notch signaling alleviated the block in stem cell differentiation. Thus Fbw7 controls neurogenesis by antagonizing Notch and c-Jun N-terminal kinase (JNK)/c-Jun signaling.

journal_name

Nat Neurosci

journal_title

Nature neuroscience

authors

Hoeck JD,Jandke A,Blake SM,Nye E,Spencer-Dene B,Brandner S,Behrens A

doi

10.1038/nn.2644

subject

Has Abstract

pub_date

2010-11-01 00:00:00

pages

1365-72

issue

11

eissn

1097-6256

issn

1546-1726

pii

nn.2644

journal_volume

13

pub_type

杂志文章
  • History-dependent variability in population dynamics during evidence accumulation in cortex.

    abstract::We studied how the posterior parietal cortex combines new information with ongoing activity dynamics as mice accumulate evidence during a virtual navigation task. Using new methods to analyze population activity on single trials, we found that activity transitioned rapidly between different sets of active neurons. Eac...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.4403

    authors: Morcos AS,Harvey CD

    更新日期:2016-12-01 00:00:00

  • Instantaneous correlation of excitation and inhibition during ongoing and sensory-evoked activities.

    abstract::Temporal and quantitative relations between excitatory and inhibitory inputs in the cortex are central to its activity, yet they remain poorly understood. In particular, a controversy exists regarding the extent of correlation between cortical excitation and inhibition. Using simultaneous intracellular recordings in p...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.2105

    authors: Okun M,Lampl I

    更新日期:2008-05-01 00:00:00

  • Hedgehog signaling from the ZLI regulates diencephalic regional identity.

    abstract::The zona limitans intrathalamica (ZLI), a narrow compartment in the vertebrate forebrain that bisects the diencephalon transversely, expresses the secreted factor sonic hedgehog (Shh). Because genetic disruption of Shh in mouse causes severe early developmental defects, this strategy has not been useful in identifying...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn1338

    authors: Kiecker C,Lumsden A

    更新日期:2004-11-01 00:00:00

  • Circuit dissection of the role of somatostatin in itch and pain.

    abstract::Stimuli that elicit itch are detected by sensory neurons that innervate the skin. This information is processed by the spinal cord; however, the way in which this occurs is still poorly understood. Here we investigated the neuronal pathways for itch neurotransmission, particularly the contribution of the neuropeptide ...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/s41593-018-0119-z

    authors: Huang J,Polgár E,Solinski HJ,Mishra SK,Tseng PY,Iwagaki N,Boyle KA,Dickie AC,Kriegbaum MC,Wildner H,Zeilhofer HU,Watanabe M,Riddell JS,Todd AJ,Hoon MA

    更新日期:2018-05-01 00:00:00

  • Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsy in infancy.

    abstract::Voltage-gated sodium channels (Na(V)) are critical for initiation of action potentials. Heterozygous loss-of-function mutations in Na(V)1.1 channels cause severe myoclonic epilepsy in infancy (SMEI). Homozygous null Scn1a-/- mice developed ataxia and died on postnatal day (P) 15 but could be sustained to P17.5 with ma...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn1754

    authors: Yu FH,Mantegazza M,Westenbroek RE,Robbins CA,Kalume F,Burton KA,Spain WJ,McKnight GS,Scheuer T,Catterall WA

    更新日期:2006-09-01 00:00:00

  • Neuronal activity modifies the chromatin accessibility landscape in the adult brain.

    abstract::Neuronal activity-induced gene expression modulates the function and plasticity of the nervous system. It is unknown whether and to what extent neuronal activity may trigger changes in chromatin accessibility, a major mode of epigenetic regulation of gene expression. Here we compared chromatin accessibility landscapes...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.4494

    authors: Su Y,Shin J,Zhong C,Wang S,Roychowdhury P,Lim J,Kim D,Ming GL,Song H

    更新日期:2017-03-01 00:00:00

  • Neuronal activity drives matching of pre- and postsynaptic function during synapse maturation.

    abstract::The structure and function of presynaptic and postsynaptic compartments varies markedly in neurons, but little is known about how they are functionally arranged with respect to each other. In rat hippocampal neurons, we found that, although they are structurally correlated from the early moments of formation, synapses...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.2826

    authors: Kay L,Humphreys L,Eickholt BJ,Burrone J

    更新日期:2011-06-01 00:00:00

  • Episodic sequence memory is supported by a theta-gamma phase code.

    abstract::The meaning we derive from our experiences is not a simple static extraction of the elements but is largely based on the order in which those elements occur. Models propose that sequence encoding is supported by interactions between high- and low-frequency oscillations, such that elements within an experience are repr...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.4374

    authors: Heusser AC,Poeppel D,Ezzyat Y,Davachi L

    更新日期:2016-10-01 00:00:00

  • Rac1 is essential in cocaine-induced structural plasticity of nucleus accumbens neurons.

    abstract::Repeated cocaine administration increases the dendritic arborization of nucleus accumbens neurons, but the underlying signaling events remain unknown. Here we show that repeated exposure to cocaine negatively regulates the active form of Rac1, a small GTPase that controls actin remodeling in other systems. Further, we...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.3094

    authors: Dietz DM,Sun H,Lobo MK,Cahill ME,Chadwick B,Gao V,Koo JW,Mazei-Robison MS,Dias C,Maze I,Damez-Werno D,Dietz KC,Scobie KN,Ferguson D,Christoffel D,Ohnishi Y,Hodes GE,Zheng Y,Neve RL,Hahn KM,Russo SJ,Nestler EJ

    更新日期:2012-06-01 00:00:00

  • Neuronal correlates of visibility and invisibility in the primate visual system.

    abstract::A brief visual target stimulus may be rendered invisible if it is immediately preceded or followed by another stimulus. This class of illusions, known as visual masking, may allow insights into the neural mechanisms that underlie visual perception. We have therefore explored the temporal characteristics of masking ill...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/393

    authors: Macknik SL,Livingstone MS

    更新日期:1998-06-01 00:00:00

  • Single-nucleus transcriptomics of the prefrontal cortex in major depressive disorder implicates oligodendrocyte precursor cells and excitatory neurons.

    abstract::Major depressive disorder (MDD) has an enormous impact on global disease burden, affecting millions of people worldwide and ranking as a leading cause of disability for almost three decades. Past molecular studies of MDD employed bulk homogenates of postmortem brain tissue, which obscures gene expression changes withi...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/s41593-020-0621-y

    authors: Nagy C,Maitra M,Tanti A,Suderman M,Théroux JF,Davoli MA,Perlman K,Yerko V,Wang YC,Tripathy SJ,Pavlidis P,Mechawar N,Ragoussis J,Turecki G

    更新日期:2020-06-01 00:00:00

  • Mitochondrial oxidant stress in locus coeruleus is regulated by activity and nitric oxide synthase.

    abstract::Loss of noradrenergic locus coeruleus (LC) neurons is a prominent feature of aging-related neurodegenerative diseases, such as Parkinson's disease (PD). The basis of this vulnerability is not understood. To explore possible physiological determinants, we studied LC neurons using electrophysiological and optical approa...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.3717

    authors: Sanchez-Padilla J,Guzman JN,Ilijic E,Kondapalli J,Galtieri DJ,Yang B,Schieber S,Oertel W,Wokosin D,Schumacker PT,Surmeier DJ

    更新日期:2014-06-01 00:00:00

  • Complete sparing of high-contrast color input to motion perception in cortical color blindness.

    abstract::It is widely held that color and motion are processed by separate parallel pathways in the visual system, but this view is difficult to reconcile with the fact that motion can be detected in equiluminant stimuli that are defined by color alone. To examine the relationship between color and motion, we tested three pati...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/688

    authors: Cavanagh P,Hénaff MA,Michel F,Landis T,Troscianko T,Intriligator J

    更新日期:1998-07-01 00:00:00

  • Synchrony-dependent propagation of firing rate in iteratively constructed networks in vitro.

    abstract::The precise role of synchronous neuronal firing in signal encoding remains unclear. To examine what kinds of signals can be carried by synchrony, I reproduced a multilayer feedforward network of neurons in an in vitro slice preparation of rat cortex using an iterative procedure. When constant and time-varying frequenc...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn1056

    authors: Reyes AD

    更新日期:2003-06-01 00:00:00

  • Genome-wide distribution of linker histone H1.0 is independent of MeCP2.

    abstract::Previous studies suggested that MeCP2 competes with linker histone H1, but this hypothesis has never been tested in vivo. Here, we performed chromatin immunoprecipitation followed by sequencing (ChIP-seq) of Flag-tagged-H1.0 in mouse forebrain excitatory neurons. Unexpectedly, Flag-H1.0 and MeCP2 occupied similar geno...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/s41593-018-0155-8

    authors: Ito-Ishida A,Yamalanchili HK,Shao Y,Baker SA,Heckman LD,Lavery LA,Kim JY,Lombardi LM,Sun Y,Liu Z,Zoghbi HY

    更新日期:2018-06-01 00:00:00

  • Gating the pore of P2X receptor channels.

    abstract::Three families of ligand-activated ion channels mediate synaptic communication between excitable cells in mammals. For pentameric channels related to nicotinic acetylcholine receptors and tetrameric channels such as glutamate receptors, the pore-forming and gate regions have been studied extensively. In contrast, litt...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.2151

    authors: Li M,Chang TH,Silberberg SD,Swartz KJ

    更新日期:2008-08-01 00:00:00

  • Heterogeneity of CNS myeloid cells and their roles in neurodegeneration.

    abstract::The diseased brain hosts a heterogeneous population of myeloid cells, including parenchymal microglia, perivascular cells, meningeal macrophages and blood-borne monocytes. To date, the different types of brain myeloid cells have been discriminated solely on the basis of their localization, morphology and surface epito...

    journal_title:Nature neuroscience

    pub_type: 杂志文章,评审

    doi:10.1038/nn.2923

    authors: Prinz M,Priller J,Sisodia SS,Ransohoff RM

    更新日期:2011-09-27 00:00:00

  • Merlin isoform 2 in neurofibromatosis type 2-associated polyneuropathy.

    abstract::The autosomal dominant disorder neurofibromatosis type 2 (NF2) is a hereditary tumor syndrome caused by inactivation of the NF2 tumor suppressor gene, encoding merlin. Apart from tumors affecting the peripheral and central nervous systems, most NF2 patients develop peripheral neuropathies. This peripheral nerve diseas...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.3348

    authors: Schulz A,Baader SL,Niwa-Kawakita M,Jung MJ,Bauer R,Garcia C,Zoch A,Schacke S,Hagel C,Mautner VF,Hanemann CO,Dun XP,Parkinson DB,Weis J,Schröder JM,Gutmann DH,Giovannini M,Morrison H

    更新日期:2013-04-01 00:00:00

  • AlphaCaMKII autophosphorylation contributes to rapid learning but is not necessary for memory.

    abstract::Autophosphorylation of alpha calcium-calmodulin-dependent kinase II (alphaCaMKII) has been proposed to be the key event in memory storage. We tested this hypothesis with autophosphorylation-deficient mutant mice in hippocampus- and amygdala-dependent learning and memory tasks and found that the autophosphorylation of ...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn1431

    authors: Irvine EE,Vernon J,Giese KP

    更新日期:2005-04-01 00:00:00

  • Capacity for 5-HT1A-mediated autoregulation predicts amygdala reactivity.

    abstract::We examined the contribution of 5-HT1A autoreceptors (with [11C]WAY100635 positron emission tomography) to amygdala reactivity (with blood oxygenation level-dependent functional magnetic resonance imaging) in 20 healthy adult volunteers. We found a significant inverse relationship wherein 5-HT1A autoreceptor density p...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn1780

    authors: Fisher PM,Meltzer CC,Ziolko SK,Price JC,Moses-Kolko EL,Berga SL,Hariri AR

    更新日期:2006-11-01 00:00:00

  • Author Correction: Using Bayes factor hypothesis testing in neuroscience to establish evidence of absence.

    abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title:Nature neuroscience

    pub_type: 已发布勘误

    doi:10.1038/s41593-020-00710-7

    authors: Keysers C,Gazzola V,Wagenmakers EJ

    更新日期:2020-11-01 00:00:00

  • An α2-Na/K ATPase/α-adducin complex in astrocytes triggers non-cell autonomous neurodegeneration.

    abstract::Perturbations of astrocytes trigger neurodegeneration in several diseases, but the glial cell-intrinsic mechanisms that induce neurodegeneration remain poorly understood. We found that a protein complex of α2-Na/K ATPase and α-adducin was enriched in astrocytes expressing mutant superoxide dismutase 1 (SOD1), which ca...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.3853

    authors: Gallardo G,Barowski J,Ravits J,Siddique T,Lingrel JB,Robertson J,Steen H,Bonni A

    更新日期:2014-12-01 00:00:00

  • Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptors.

    abstract::Dopamine (DA) D2 receptors expressed in DA neurons (D2 autoreceptors) exert a negative feedback regulation that reduces DA neuron firing, DA synthesis and DA release. As D2 receptors are mostly expressed in postsynaptic neurons, pharmacological and genetic approaches have been unable to definitively address the in viv...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.2862

    authors: Bello EP,Mateo Y,Gelman DM,Noaín D,Shin JH,Low MJ,Alvarez VA,Lovinger DM,Rubinstein M

    更新日期:2011-07-10 00:00:00

  • Hotspots of missense mutation identify neurodevelopmental disorder genes and functional domains.

    abstract::Although de novo missense mutations have been predicted to account for more cases of autism than gene-truncating mutations, most research has focused on the latter. We identified the properties of de novo missense mutations in patients with neurodevelopmental disorders (NDDs) and highlight 35 genes with excess missens...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.4589

    authors: Geisheker MR,Heymann G,Wang T,Coe BP,Turner TN,Stessman HAF,Hoekzema K,Kvarnung M,Shaw M,Friend K,Liebelt J,Barnett C,Thompson EM,Haan E,Guo H,Anderlid BM,Nordgren A,Lindstrand A,Vandeweyer G,Alberti A,Avola E,V

    更新日期:2017-08-01 00:00:00

  • Modeling behaviorally relevant neural dynamics enabled by preferential subspace identification.

    abstract::Neural activity exhibits complex dynamics related to various brain functions, internal states and behaviors. Understanding how neural dynamics explain specific measured behaviors requires dissociating behaviorally relevant and irrelevant dynamics, which is not achieved with current neural dynamic models as they are le...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/s41593-020-00733-0

    authors: Sani OG,Abbaspourazad H,Wong YT,Pesaran B,Shanechi MM

    更新日期:2021-01-01 00:00:00

  • Target-cell-specific facilitation and depression in neocortical circuits.

    abstract::In neocortical circuits, repetitively active neurons evoke unitary postsynaptic potentials (PSPs) whose peak amplitudes either increase (facilitate) or decrease (depress) progressively. To examine the basis for these different synaptic responses, we made simultaneous recordings from three classes of neurons in cortica...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/1092

    authors: Reyes A,Lujan R,Rozov A,Burnashev N,Somogyi P,Sakmann B

    更新日期:1998-08-01 00:00:00

  • Cortical tracking of hierarchical linguistic structures in connected speech.

    abstract::The most critical attribute of human language is its unbounded combinatorial nature: smaller elements can be combined into larger structures on the basis of a grammatical system, resulting in a hierarchy of linguistic units, such as words, phrases and sentences. Mentally parsing and representing such structures, howev...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.4186

    authors: Ding N,Melloni L,Zhang H,Tian X,Poeppel D

    更新日期:2016-01-01 00:00:00

  • Expert face processing requires visual input to the right hemisphere during infancy.

    abstract::Adult expertise in face processing is mediated largely by neural networks in the right hemisphere. Here we evaluate the contribution of early visual input in establishing this neural substrate. We compared visually normal individuals to patients for whom visual input had been restricted mainly to one hemisphere during...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn1121

    authors: Le Grand R,Mondloch CJ,Maurer D,Brent HP

    更新日期:2003-10-01 00:00:00

  • Anatomical connectivity patterns predict face selectivity in the fusiform gyrus.

    abstract::A fundamental assumption in neuroscience is that brain structure determines function. Accordingly, functionally distinct regions of cortex should be structurally distinct in their connections to other areas. We tested this hypothesis in relation to face selectivity in the fusiform gyrus. By using only structural conne...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/nn.3001

    authors: Saygin ZM,Osher DE,Koldewyn K,Reynolds G,Gabrieli JD,Saxe RR

    更新日期:2011-12-25 00:00:00

  • Vector trace cells in the subiculum of the hippocampal formation.

    abstract::Successfully navigating in physical or semantic space requires a neural representation of allocentric (map-based) vectors to boundaries, objects and goals. Cognitive processes such as path-planning and imagination entail the recall of vector representations, but evidence of neuron-level memory for allocentric vectors ...

    journal_title:Nature neuroscience

    pub_type: 杂志文章

    doi:10.1038/s41593-020-00761-w

    authors: Poulter S,Lee SA,Dachtler J,Wills TJ,Lever C

    更新日期:2020-12-21 00:00:00