Abstract：
:Relative quiescence and self renewal are defining features of adult stem cells, but their potential coordination remains unclear. Subependymal neural stem cells (NSCs) lacking cyclin-dependent kinase (CDK) inhibitor (CKI) 1a (p21) exhibit rapid expansion that is followed by their permanent loss later in life. Here we demonstrate that transcription of the gene encoding bone morphogenetic protein 2 (Bmp2) in NSCs is under the direct negative control of p21 through actions that are independent of CDK. Loss of p21 in NSCs results in increased levels of secreted BMP2, which induce premature terminal differentiation of multipotent NSCs into mature non-neurogenic astrocytes in an autocrine and/or paracrine manner. We also show that the cell-nonautonomous p21-null phenotype is modulated by the Noggin-rich environment of the subependymal niche. The dual function that we describe here provides a physiological example of combined cell-autonomous and cell-nonautonomous functions of p21 with implications in self renewal, linking the relative quiescence of adult stem cells to their longevity and potentiality.
journal_name
Nat Neuroscijournal_title
Nature neuroscienceauthors
Porlan E,Morante-Redolat JM,Marqués-Torrejón MÁ,Andreu-Agulló C,Carneiro C,Gómez-Ibarlucea E,Soto A,Vidal A,Ferrón SR,Fariñas Idoi
10.1038/nn.3545subject
Has Abstractpub_date
2013-11-01 00:00:00pages
1567-75issue
11eissn
1097-6256issn
1546-1726pii
nn.3545journal_volume
16pub_type
杂志文章abstract：:The development of neuronal networks in the neocortex depends on control mechanisms for mitosis and migration that allow newborn neurons to find their accurate position. Multiple mitogens, neurotrophic factors, guidance molecules and their corresponding receptors are involved in this process, but the mechanisms by whi...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3333
更新日期：2013-04-01 00:00:00
abstract：:The molecular basis of CNS myelin regeneration (remyelination) is poorly understood. We generated a comprehensive transcriptional profile of the separate stages of spontaneous remyelination that follow focal demyelination in the rat CNS and found that transcripts that encode the retinoid acid receptor RXR-γ were diffe...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.2702
更新日期：2011-01-01 00:00:00
abstract：:We report a systematic relationship between sound-frequency tuning and sensitivity to interaural time delays for neurons in the midbrain nucleus of the inferior colliculus; neurons with relatively low best frequencies (BFs) showed response peaks at long delays, whereas neurons with relatively high BFs showed response ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/86049
更新日期：2001-04-01 00:00:00
abstract：:Dopamine is vital for coordinated motion and for association learning linked to behavioral reinforcement. Here we show that the precise overlap of striatal dopaminergic and cholinergic fibers underlies potent control of dopamine release by ongoing nicotinic receptor activity. In mouse striatal slices, nicotinic antago...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn769
更新日期：2001-12-01 00:00:00
abstract：:Lis1 gene defects impair neuronal migration, causing the severe human brain malformation lissencephaly. Although much is known about its interactions with microtubules, microtubule-binding proteins such as CLIP-170, and with the dynein motor complex, the response of Lis1 to neuronal motility signals has not been eluci...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1619
更新日期：2006-01-01 00:00:00
abstract：:In severe hypoxia, homeostatic mechanisms maintain function of the brainstem respiratory network. We hypothesized that hypoxia involves a transition from neuronal mechanisms of normal breathing (eupnea) to a rudimentary pattern of inspiratory movements (gasping). We provide evidence for hypoxia-driven transformation w...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1650
更新日期：2006-03-01 00:00:00
abstract：:Central pattern generators (CPGs) are spinal neuronal networks required for locomotion. Glutamatergic neurons have been implicated as being important for intrinsic rhythm generation in the CPG and for the command signal for initiating locomotion, although this has not been demonstrated directly. We used a newly genera...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.2482
更新日期：2010-02-01 00:00:00
abstract：:The ability to attribute mental states to others, and therefore to predict others' behavior, is particularly advanced in humans. A controversial but untested idea is that this is achieved by simulating the other person's mental processes in one's own mind. If this is the case, then the same neural systems activated by...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1168
更新日期：2004-01-01 00:00:00
abstract：:The mammalian visual system contains an extensive web of feedback connections projecting from higher cortical areas to lower areas, including primary visual cortex. Although multiple theories have been proposed, the role of these connections in perceptual processing is not understood. We found that the pattern of func...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.2218
更新日期：2008-12-01 00:00:00
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
更新日期：2016-12-01 00:00:00
abstract：:A central question in the study of human behavior is the origin of willed action. EEG recordings of surface brain activity from human subjects performing a self-initiated movement show that the subjective experience of wanting to move follows, rather than precedes, the 'readiness potential'--an electrophysiological ma...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1160
更新日期：2004-01-01 00:00:00
abstract：:En route to their target, pioneering motor growth cones repeatedly encounter choice points at which they make pathway decisions. In the zebrafish mutant unplugged, two of the three segmental motor axons make incorrect decisions at a somitic choice point. Using positional cloning, we show here that unplugged encodes a ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1350
更新日期：2004-12-01 00:00:00
abstract：:Forces developed by cochlear outer hair cells (OHCs) are responsible for the sharp tuning that underlies sensitivity and frequency selectivity in the ear. OHCs exhibit a voltage-dependent motility involving a 'motor' protein embedded in the basolateral membrane. The motor has so far resisted molecular identification. ...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/11174
更新日期：1999-08-01 00:00:00
abstract：:Humans have ~400 intact odorant receptors, but each individual has a unique set of genetic variations that lead to variation in olfactory perception. We used a heterologous assay to determine how often genetic polymorphisms in odorant receptors alter receptor function. We identified agonists for 18 odorant receptors a...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.3598
更新日期：2014-01-01 00:00:00
abstract：:Trafficking of AMPA receptors (AMPARs) is important for many forms of synaptic plasticity. However, the link between activity and resulting synaptic alterations is not fully understood. We identified a direct interaction between N-ethylmaleimide-sensitive fusion protein (NSF), an ATPase involved in membrane fusion eve...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.2624
更新日期：2010-10-01 00:00:00
abstract：:Behavior-contingent network oscillations bring about transient, functionally coherent neuronal assemblies in the cerebral cortex, including the hippocampus. Inhibitory input on and close to the soma is believed to phase intrinsic oscillations and output of pyramidal cells, but the function of GABA release to pyramidal...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1159
更新日期：2004-01-01 00:00:00
abstract：:GABA interneurons play a critical role in higher brain functions. Astrocytic glial cells interact with synapses throughout the whole brain and are recognized as regulatory elements of excitatory synaptic transmission. However, it is largely unknown how GABAergic interneurons and astrocytes interact and contribute to s...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/s41593-020-00752-x
更新日期：2021-01-01 00:00:00
abstract：:The neural mechanisms that mediate the transition from a drug-naive state to a state of drug dependence and addiction are not yet known. Here we show that a discrete population of GABA(A) receptors in the mammalian ventral tegmental area (VTA) serves as a potential addiction switching mechanism by gating reward transm...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1182
更新日期：2004-02-01 00:00:00
abstract：:Transposable elements, known colloquially as 'jumping genes', constitute approximately 45% of the human genome. Cells utilize epigenetic defenses to limit transposable element jumping, including formation of silencing heterochromatin and generation of piwi-interacting RNAs (piRNAs), small RNAs that facilitate clearanc...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/s41593-018-0194-1
更新日期：2018-08-01 00:00:00
abstract：:Projection neurons migrate from the ventricular zone to the neocortical plate during the development of the mouse brain. Their overall movement is radial, but they become multipolar and move nonradially in the intermediate zone. Here we show that Reelin, the Rap1 GTPase and N-cadherin (NCad) are important for multipol...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.2816
更新日期：2011-06-01 00:00:00
abstract：:It is widely accepted that D1 dopamine receptor-expressing striatal neurons convey their information directly to the output nuclei of the basal ganglia, whereas D2-expressing neurons do so indirectly via pallidal neurons. Combining optogenetics and electrophysiology, we found that this architecture does not apply to m...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.4068
更新日期：2015-09-01 00:00:00
abstract：:The deposition of aggregated amyloid-β peptides derived from the pro-amyloidogenic processing of the amyloid precurson protein (APP) into characteristic amyloid plaques (APs) is distinctive to Alzheimer's disease (AD). Alternative APP processing via the metalloprotease ADAM10 prevents amyloid-β formation. We tested wh...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/s41593-019-0432-1
更新日期：2019-08-01 00:00:00
abstract：:Modeling of human neuropsychiatric disorders in animals is extremely challenging given the subjective nature of many symptoms, the lack of biomarkers and objective diagnostic tests, and the early state of the relevant neurobiology and genetics. Nonetheless, progress in understanding pathophysiology and in treatment de...
journal_title：Nature neuroscience
pub_type： 杂志文章,评审
doi：10.1038/nn.2647
更新日期：2010-10-01 00:00:00
abstract：:We argue that there will be no single (genetic or cognitive) cause for the diverse symptoms defining autism. We present recent evidence of behavioral fractionation of social impairment, communication difficulties and rigid and repetitive behaviors. Twin data suggest largely nonoverlapping genes acting on each of these...
journal_title：Nature neuroscience
pub_type： 杂志文章,评审
doi：10.1038/nn1770
更新日期：2006-10-01 00:00:00
abstract：:As the neural network becomes wired, postsynaptic signaling molecules are thought to control the growth of dendrites and synapses. However, how these molecules are coordinated to sculpt postsynaptic structures is less well understood. We find that ephrin-B3, a transmembrane ligand for Eph receptors, functions postsyna...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.2931
更新日期：2011-10-02 00:00:00
abstract：:The brain transforms physical sensory stimuli into meaningful perceptions. In animals making choices about sensory stimuli, neuronal activity in successive cortical stages reflects a progression from sensation to decision. Feedforward and feedback pathways connecting cortical areas are critical for this transformation...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.4356
更新日期：2016-09-01 00:00:00
abstract：:PICALM is a highly validated genetic risk factor for Alzheimer's disease (AD). We found that reduced expression of PICALM in AD and murine brain endothelium correlated with amyloid-β (Aβ) pathology and cognitive impairment. Moreover, Picalm deficiency diminished Aβ clearance across the murine blood-brain barrier (BBB)...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.4025
更新日期：2015-07-01 00:00:00
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
更新日期：2018-06-01 00:00:00
abstract：:Tau protein can transfer between neurons transneuronally and trans-synaptically, which is thought to explain the progressive spread of tauopathy observed in the brain of patients with Alzheimer's disease. Here we show that physiological tau released from donor cells can transfer to recipient cells via the medium, sugg...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.4328
更新日期：2016-08-01 00:00:00
abstract：:Communication between glia cells and neurons is crucial for brain functions, but the molecular mechanisms and functional consequences of gliotransmission remain enigmatic. Here we report that astrocytes express synaptobrevin II and cellubrevin as functionally non-overlapping vesicular SNARE proteins on glutamatergic v...
journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn.4647
更新日期：2017-11-01 00:00:00
