Neurogenesis (Austin, Tex.)最新文献_第9页

Neuronal specification exploits the inherent flexibility of cell-cycle gap phases. 神经元规范利用细胞周期间隙期固有的灵活性。

Neurogenesis (Austin, Tex.) Pub Date : 2015-11-13 eCollection Date: 2015-01-01 DOI: 10.1080/23262133.2015.1095694

Benjamin Pfeuty

{"title":"Neuronal specification exploits the inherent flexibility of cell-cycle gap phases.","authors":"Benjamin Pfeuty","doi":"10.1080/23262133.2015.1095694","DOIUrl":"https://doi.org/10.1080/23262133.2015.1095694","url":null,"abstract":"Starting from pluripotent stem cells that virtually proliferate indefinitely, the orderly emergence during organogenesis of lineage-restricted cell types exhibiting a decreased proliferative capacity concurrently with an increasing range of differentiation traits implies the occurrence of a stringent spatiotemporal coupling between cell-cycle progression and cell differentiation. A recent computational modeling study has explored in the context of neurogenesis whether and how the peculiar pattern of connections among the proneural Neurog2 factor, the Hes1 Notch effector and antagonistically-acting G1-phase regulators would be instrumental in this event. This study highlighted that the strong opposition to G1/S transit imposed by accumulating Neurog2 and CKI enables a sensitive control of G1-phase lengthening and terminal differentiation to occur concomitantly with late-G1 exit. Contrastingly, Hes1 promotes early-G1 cell-cycle arrest and its cell-autonomous oscillations combined with a lateral inhibition mechanism help maintain a labile proliferation state in dynamic balance with diverse cell-fate outputs, thereby, offering cells the choice to either keep self-renewing or differentiate into distinct cell types. These results, discussed in connection with Ascl1-dependent neural differentiation, suggest that developmental fate decisions exploit the inherent flexibility of cell-cycle gap phases to generate diversity by selecting subtly-differing patterns of connections among components of the cell-cycle machinery and differentiation pathways. ","PeriodicalId":74274,"journal":{"name":"Neurogenesis (Austin, Tex.)","volume":" ","pages":"e1095694"},"PeriodicalIF":0.0,"publicationDate":"2015-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23262133.2015.1095694","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34372934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Rheb1 mediates DISC1-dependent regulation of new neuron development in the adult hippocampus. Rheb1介导成人海马中依赖disc1的新神经元发育调控。

Neurogenesis (Austin, Tex.) Pub Date : 2015-11-10 eCollection Date: 2015-01-01 DOI: 10.1080/23262133.2015.1081715

Eunchai Kang, Ju Young Kim, Cindy Y Liu, Bo Xiao, Po Yu Chen, Kimberly M Christian, Paul F Worley, Hongjun Song, Guo-Li Ming

{"title":"Rheb1 mediates DISC1-dependent regulation of new neuron development in the adult hippocampus.","authors":"Eunchai Kang, Ju Young Kim, Cindy Y Liu, Bo Xiao, Po Yu Chen, Kimberly M Christian, Paul F Worley, Hongjun Song, Guo-Li Ming","doi":"10.1080/23262133.2015.1081715","DOIUrl":"https://doi.org/10.1080/23262133.2015.1081715","url":null,"abstract":"A large number of susceptibility genes have been implicated in psychiatric disorders with a developmental origin, yet their biological roles and signaling mechanisms in neurodevelopment are largely unknown. Disrupted-In-Schizophrenia 1 (DISC1), a susceptibility gene for several major psychiatric disorders, regulates the development of newborn neurons in the adult hippocampus. Systemic pharmacological inhibition of mTOR signaling with rapamycin has been shown to rescue DISC1 deficiency-induced neurodevelopmental defects, as well as cognitive and affective deficits. Whether mTOR signaling plays a cell-autonomous and/or non-cell-autonomous role in DISC1-dependent regulation of neuronal development is not clear. Here we provide genetic evidence that hyper-activation of mTOR activator Rheb1 (Ras homolog enriched in brain 1) in newborn neurons recapitulates DISC1 deficiency-induced neurodevelopmental defects, including neuronal morphogenesis and migration. We further show that genetic deletion of Rheb1 rescues those defects in a cell-autonomous fashion in developing newborn neurons in the adult hippocampus. Our genetic and functional studies demonstrate that Rheb1 acts as a key mediator of DISC1-dependent regulation of mTOR signaling and neuronal development during adult hippocampal neurogenesis. ","PeriodicalId":74274,"journal":{"name":"Neurogenesis (Austin, Tex.)","volume":" ","pages":"e1081715"},"PeriodicalIF":0.0,"publicationDate":"2015-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23262133.2015.1081715","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34372933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Dissecting the role of Wnt signaling and its interactions with FGF signaling during midbrain neurogenesis. 剖析Wnt信号在中脑神经发生中的作用及其与FGF信号的相互作用。

Neurogenesis (Austin, Tex.) Pub Date : 2015-09-21 eCollection Date: 2015-01-01 DOI: 10.1080/23262133.2015.1057313

Carlene Dyer, Eric Blanc, Rob J Stanley, Robert D Knight

{"title":"Dissecting the role of Wnt signaling and its interactions with FGF signaling during midbrain neurogenesis.","authors":"Carlene Dyer, Eric Blanc, Rob J Stanley, Robert D Knight","doi":"10.1080/23262133.2015.1057313","DOIUrl":"https://doi.org/10.1080/23262133.2015.1057313","url":null,"abstract":"Interactions between FGF and Wnt/ bcat signaling control development of the midbrain. The nature of this interaction and how these regulate patterning, growth and differentiation is less clear, as it has not been possible to temporally dissect the effects of one pathway relative to the other. We have employed pharmacological and genetic tools to probe the temporal and spatial roles of FGF and Wnt in controlling the specification of early midbrain neurons. We identify a β-catenin (bcat) independent role for GSK-3 in modulating FGF activity and hence neuronal patterning. This function is complicated by an overlap with bcat-dependent regulation of FGF signaling, through the regulation of sprouty4. Additionally we reveal how attenuation of Axin protein function can promote fluctuating levels of bcat activity that are dependent on FGF activity. This highlights the complex nature of the interactions between FGF and Wnt/ bcat and reveals that they act at multiple levels to control each others activity in the midbrain. ","PeriodicalId":74274,"journal":{"name":"Neurogenesis (Austin, Tex.)","volume":" ","pages":"e1057313"},"PeriodicalIF":0.0,"publicationDate":"2015-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23262133.2015.1057313","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34371980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

The Purkinje neuron: A central orchestrator of cerebellar neurogenesis. 浦肯野神经元:小脑神经发生的中枢指挥。

Neurogenesis (Austin, Tex.) Pub Date : 2015-09-17 eCollection Date: 2015-01-01 DOI: 10.1080/23262133.2015.1025940

Jonathan Fleming, Chin Chiang

{"title":"The Purkinje neuron: A central orchestrator of cerebellar neurogenesis.","authors":"Jonathan Fleming, Chin Chiang","doi":"10.1080/23262133.2015.1025940","DOIUrl":"https://doi.org/10.1080/23262133.2015.1025940","url":null,"abstract":"Within the cyto-architecture of the brain is an often complex, but balanced, neuronal circuitry, the successful construction of which relies on the coordinated generation of functionally opposed neurons. Indeed, deregulated production of excitatory/inhibitory interneurons can greatly disrupt the integrity of excitatory/inhibitory neuronal transmission, which is a hallmark of neurodevelopmental disorders such as autism. Recent work has demonstrated that the Purkinje neuron, the central integrator of signaling within the cerebellar system, acts during development to ensure that neurogenesis occurring in spatially opposed domains reaches completion by transmitting the Sonic hedgehog ligand bi-directionally. In addition to a classic role in driving granule cell precursor proliferation, we now know that Purkinje neuron-derived Sonic hedgehog is simultaneously disseminated to the neonatal white matter. Within this neurogenic niche a lineage of Shh-responding stem and progenitor cells expand pools of GABAergic interneuron and astrocyte precursors. These recent findings advance our understanding of how Purkinje neurons function dynamically to oversee completion of a balanced cerebellar circuit. ","PeriodicalId":74274,"journal":{"name":"Neurogenesis (Austin, Tex.)","volume":" ","pages":"e1025940"},"PeriodicalIF":0.0,"publicationDate":"2015-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23262133.2015.1025940","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34727569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12

Regulation of hippocampal memory traces by neurogenesis. 神经发生对海马记忆痕迹的调节。

Neurogenesis (Austin, Tex.) Pub Date : 2015-09-17 eCollection Date: 2015-01-01 DOI: 10.1080/23262133.2015.1025180

Christoph Anacker, Christine Ann Denny, René Hen

{"title":"Regulation of hippocampal memory traces by neurogenesis.","authors":"Christoph Anacker, Christine Ann Denny, René Hen","doi":"10.1080/23262133.2015.1025180","DOIUrl":"https://doi.org/10.1080/23262133.2015.1025180","url":null,"abstract":"The hippocampus has long been known as a brain structure fundamental for memory formation and retrieval. Recent technological advances of cellular tracing techniques and optogenetic manipulation strategies have allowed to unravel important aspects of the cellular origin of memory, and have started to shed new light on the neuronal networks involved in encoding, consolidation and retrieval of memory in the hippocampus. In particular, memory traces, or engrams, that are formed during encoding in the dentate gyrus and CA3 region are crucial for memory retrieval and amenable to modulation by neuroplastic mechanisms, including adult hippocampal neurogenesis. Here, we will discuss how memory traces are being encoded at the cellular level, how they may contribute to pattern separation and pattern completion in the hippocampus, and how they can be associated with different experiences to express memories of opposite valence. We propose a mechanism by which adult hippocampal neurogenesis may contribute to the formation of engrams, which may be relevant not only for the encoding of contextual information, but also for mood abnormalities, such as anxiety and depression. ","PeriodicalId":74274,"journal":{"name":"Neurogenesis (Austin, Tex.)","volume":" ","pages":"e1025180"},"PeriodicalIF":0.0,"publicationDate":"2015-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23262133.2015.1025180","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34370395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Harnessing the master transcriptional repressor REST to reciprocally regulate neurogenesis. 利用主转录抑制因子REST相互调节神经发生。

Neurogenesis (Austin, Tex.) Pub Date : 2015-08-18 eCollection Date: 2015-01-01 DOI: 10.1080/23262133.2015.1055419

Edmund Nesti

{"title":"Harnessing the master transcriptional repressor REST to reciprocally regulate neurogenesis.","authors":"Edmund Nesti","doi":"10.1080/23262133.2015.1055419","DOIUrl":"https://doi.org/10.1080/23262133.2015.1055419","url":null,"abstract":"Neurogenesis begins in embryonic development and continues at a reduced rate into adulthood in vertebrate species, yet the signaling cascades regulating this process remain poorly understood. Plasma membrane-initiated signaling cascades regulate neurogenesis via downstream pathways including components of the transcriptional machinery. A nuclear factor that temporally regulates neurogenesis by repressing neuronal differentiation is the repressor element 1 (RE1) silencing transcription (REST) factor. We have recently discovered a regulatory site on REST that serves as a molecular switch for neuronal differentiation. Specifically, C-terminal domain small phosphatase 1, CTDSP1, present in non-neuronal cells, maintains REST activity by dephosphorylating this site. Reciprocally, extracellular signal-regulated kinase, ERK, activated by growth factor signaling in neural progenitors, and peptidylprolyl cis/trans isomerase Pin1, decrease REST activity through phosphorylation-dependent degradation. Our findings further resolve the mechanism for temporal regulation of REST and terminal neuronal differentiation. They also provide new potential therapeutic targets to enhance neuronal regeneration after injury. ","PeriodicalId":74274,"journal":{"name":"Neurogenesis (Austin, Tex.)","volume":" ","pages":"e1055419"},"PeriodicalIF":0.0,"publicationDate":"2015-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23262133.2015.1055419","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34659595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Multi-site phospho-regulation of proneural transcription factors controls proliferation versus differentiation in development and reprogramming. 前神经转录因子的多位点磷酸化调控控制发育和重编程中的增殖与分化。

Neurogenesis (Austin, Tex.) Pub Date : 2015-08-07 eCollection Date: 2015-01-01 DOI: 10.1080/23262133.2015.1049733

Anna Philpott

{"title":"Multi-site phospho-regulation of proneural transcription factors controls proliferation versus differentiation in development and reprogramming.","authors":"Anna Philpott","doi":"10.1080/23262133.2015.1049733","DOIUrl":"10.1080/23262133.2015.1049733","url":null,"abstract":"During development of the nervous system, it is essential to co-ordinate the processes of proliferation and differentiation. Basic helix-loop-helix transcription factors play a central role in controlling neuronal differentiation and maturation as well as being components of the combinatorial code that determines neuronal identity. We have recently shown that the ability of the proneural proteins Ngn2 and Ascl1 to drive neuronal differentiation is inhibited by cyclin dependent kinase-mediated multi-site phosphorylation. This limits downstream target promoter dwell time, thus demonstrating a direct mechanistic regulatory link between the cell cycle and differentiation machinery.Proneural proteins are key components of transcription factor cocktails that can bring about the direct reprogramming of human fibroblasts into neurons. Building on our observations demonstrating that phospho-mutant proneural proteins show an enhanced ability to drive neuronal differentiation in vivo, we see that replacing wild-type with phospho-mutant proneural proteins in fibroblast reprogramming cocktails significantly enhances the axonal outgrowth, branching and electrophysiological maturity of the neurons generated. A model is presented here that can explain the enhanced ability of dephosphorylated proneural proteins to drive neuronal differentiation, and some unanswered questions in this emerging area are highlighted. ","PeriodicalId":74274,"journal":{"name":"Neurogenesis (Austin, Tex.)","volume":"2 1","pages":"e1049733"},"PeriodicalIF":0.0,"publicationDate":"2015-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23262133.2015.1049733","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9152713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

Identification and expression patterns of novel long non-coding RNAs in neural progenitors of the developing mammalian cortex. 发育中的哺乳动物皮层神经祖细胞中新型长链非编码rna的鉴定和表达模式。

Neurogenesis (Austin, Tex.) Pub Date : 2015-04-11 eCollection Date: 2015-01-01 DOI: 10.1080/23262133.2014.995524

Julieta Aprea, Mathias Lesche, Simone Massalini, Silvia Prenninger, Dimitra Alexopoulou, Andreas Dahl, Michael Hiller, Federico Calegari

引用次数: 13

Making a mes: A transcription factor-microRNA pair governs the size of the midbrain and the dopaminergic progenitor pool. 制造mes:转录因子- microrna对控制着中脑和多巴胺能祖细胞库的大小。

Neurogenesis (Austin, Tex.) Pub Date : 2015-03-09 eCollection Date: 2015-01-01 DOI: 10.1080/23262133.2014.998101

Angela Anderegg, Rajeshwar Awatramani

{"title":"Making a mes: A transcription factor-microRNA pair governs the size of the midbrain and the dopaminergic progenitor pool.","authors":"Angela Anderegg, Rajeshwar Awatramani","doi":"10.1080/23262133.2014.998101","DOIUrl":"https://doi.org/10.1080/23262133.2014.998101","url":null,"abstract":"Canonical Wnt signaling is critical for midbrain dopaminergic progenitor specification, proliferation, and neurogenesis. Yet mechanisms that control Wnt signaling remain to be fully elucidated. Wnt1 is a key ligand in the embryonic midbrain, and directs proliferation, survival, specification and neurogenesis. In a recent study, we reveal that the transcription factor Lmx1b promotes Wnt1/Wnt signaling, and dopaminergic progenitor expansion, consistent with earlier studies. Additionally, Lmx1b drives expression of a non-coding RNA called Rmst, which harbors miR135a2 in its last intron. miR135a2 in turn targets Lmx1b as well as several Wnt pathway targets. Conditional overexpression of miR135a2 in the midbrain, particularly during an early time, results in a decreased dopaminergic progenitor pool, and less dopaminergic neurons, consistent with decreased Wnt signaling. We propose a model in which Lmx1b and miR135a2 influence levels of Wnt1 and Wnt signaling, and expansion of the dopaminergic progenitor pool. Further loss of function experiments and biochemical validation of targets will be critical to verify this model. Wnt agonists have recently been utilized for programming stem cells toward a dopaminergic fate in vitro, highlighting the importance of agents that modulate the Wnt pathway. ","PeriodicalId":74274,"journal":{"name":"Neurogenesis (Austin, Tex.)","volume":" ","pages":"e998101"},"PeriodicalIF":0.0,"publicationDate":"2015-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/23262133.2014.998101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34739959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

MicroRNAs of the miR379-410 cluster: New players in embryonic neurogenesis and regulators of neuronal function. miR379-410簇的microrna:胚胎神经发生和神经元功能调节的新参与者。

Neurogenesis (Austin, Tex.) Pub Date : 2015-03-04 eCollection Date: 2015-01-01 DOI: 10.1080/23262133.2015.1004970

Jennifer Winter

引用次数: 37