Dynamic signaling for neural stem cell fate determination

Wen, Sijian; Li, Hong; Liu, Jia

doi:10.4161/cam.3.1.7602

Cited by 53 publications

(48 citation statements)

References 125 publications

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“…Because inhibition of Notch signaling in neuronal progenitor cells promotes neuronal differentiation (Wen et al, 2009 ; Louvi and Artavanis-Tsakonas, 2006), we investigated the role of LncND in neuronal differentiation by RNAseq. We took advantage of SHSY5Y cells, which can differentiate into neurons in the presence of all-trans retinoic acid (Constantinescu et al, 2007).…”

Section: Resultsmentioning

confidence: 99%

A Primate lncRNA Mediates Notch Signaling during Neuronal Development by Sequestering miRNA

Rani

Nowakowski

Zhou

et al. 2016

Neuron

121

115

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Summary Long non-coding RNAs (lncRNAs) are a diverse and poorly conserved category of transcripts that have expanded greatly in primates, particularly in the brain. We identified a lncRNA, which has acquired 16 microRNA response elements for miR-143-3p in the Catarrhini branch of primates. This lncRNA termed LncND (neuro-development) is expressed in neural progenitor cells and then declines in neurons. Binding and release of miR-143-3p, by LncND, controls the expression of Notch receptors. LncND expression is enriched in radial glia cells (RGCs) in the ventricular and subventricular zones of developing human brain. Down-regulation in neuroblastoma cells reduced cell proliferation and induced neuronal differentiation, an effect phenocopied by miR-143-3p over-expression. Gain-of-function of LncND in developing mouse cortex led to an expansion of PAX6+ RGCs. These findings support role for LncND in miRNA-mediated regulation of Notch signaling within the neural progenitor pool in primates that may have contributed to the expansion of cerebral cortex.

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Section: Resultsmentioning

confidence: 99%

A Primate lncRNA Mediates Notch Signaling during Neuronal Development by Sequestering miRNA

Rani

Nowakowski

Zhou

et al. 2016

Neuron

121

115

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“…Of particular interest are the Notch components Hey2 and Heyl , which are transcription factor effectors of the Notch pathway. Hey2 particularly acts to inhibit transcription of proneural factors in association with histone deacetylase 2, to allow for stem cell maintenance and retention of pluripotency (Wen, Li, & Liu, 2009: Zhou, Kumari, Xiao, & Tan, 2010). Thus, PAE may induce rapid differentiation of NPCs by reducing these Notch effectors; however, reduced Gdnf , which has been demonstrated to increase differentiation when applied to cell culture, does not support this assessment (Roussa & Krieglstein, 2004).…”

Section: Discussionmentioning

confidence: 99%

Prenatal alcohol exposure alters expression of neurogenesis-related genes in an ex vivo cell culture model

Tyler

Allan

2014

Alcohol

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Prenatal alcohol exposure can lead to long-lasting changes in functional and genetic programs of the brain, which may underlie behavioral alterations seen in Fetal Alcohol Spectrum Disorder (FASD). Aberrant fetal programming during gestational alcohol exposure is a possible mechanism by which alcohol imparts teratogenic effects on the brain; however, current methods used to investigate the effects of alcohol on development often rely on either direct application of alcohol in vitro or acute high doses in vivo. In this study, we used our established moderate prenatal alcohol exposure (PAE) model, resulting in maternal blood alcohol content of approximately 20 mM, and subsequent ex vivo cell culture to assess expression of genes related to neurogenesis. Proliferating and differentiating neural progenitor cell culture conditions were established from telencephalic tissue derived from embryonic day (E) 15–17 tissue exposed to alcohol via maternal drinking throughout pregnancy. Gene expression analysis on mRNA derived in vitro was performed using a microarray, and quantitative PCR was conducted for genes to validate the microarray. Student's t tests were performed for statistical comparison of each exposure under each culture condition using a 95% confidence interval. Eleven percent of genes on the array had significantly altered mRNA expression in the prenatal alcohol-exposed neural progenitor culture under proliferating conditions. These include reduced expression of Adora2a, Cxcl1, Dlg4, Hes1, Nptx1, and Vegfa and increased expression of Fgf13, Ndn, and Sox3; bioinformatics analysis indicated that these genes are involved in cell growth and proliferation. Decreased levels of Dnmt1 and Dnmt3a were also found under proliferating conditions. Under differentiating conditions, 7.3% of genes had decreased mRNA expression; these include Cdk5rap3, Gdnf, Hey2, Heyl, Pard6b, and Ptn, which are associated with survival and differentiation as indicated by bioinformatics analysis. This study is the first to use chronic low to moderate PAE, to more accurately reflect maternal alcohol consumption, and subsequent neural progenitor cell culture to demonstrate that PAE throughout gestation alters expression of genes involved in neural development and embryonic neurogenesis.

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“…The importance of chemical cues in cellular differentiation, cell migration, and axon guidance is well established. Proteins known as morphogens specify the fates of neural precursors (reviewed in Wen et al, 2009), and protein cues in the extracellular space guide cell migration and axon extension (reviewed in Raper and Mason, 2010). …”

Section: Introductionmentioning

confidence: 99%

Biophysics of substrate interaction: Influence on neural motility, differentiation, and repair

Moore

Sheetz

2011

Developmental Neurobiology

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The identity and behavior of a cell is shaped by the molecular and mechanical composition of its surroundings. Molecular cues have firmly established roles in guiding both neuronal fate decisions and the migration of cells and axons. However, there is growing evidence that topographical and rigidity cues in the extracellular environment act synergistically with these molecular cues. Like chemical cues, physical factors do not elicit a fixed response, but rather one that depends on the sensory makeup of the cell. Moreover, from developmental studies and the plasticity of neural tissue, it is evident that there is dynamic feedback between physical and chemical factors to produce the final morphology. Here we focus on our current understanding of how these physical cues shape cellular differentiation and migration, and discuss their relevance to repairing the injured nervous system.

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Dynamic signaling for neural stem cell fate determination

Cited by 53 publications

References 125 publications

A Primate lncRNA Mediates Notch Signaling during Neuronal Development by Sequestering miRNA

A Primate lncRNA Mediates Notch Signaling during Neuronal Development by Sequestering miRNA

Prenatal alcohol exposure alters expression of neurogenesis-related genes in an ex vivo cell culture model

Biophysics of substrate interaction: Influence on neural motility, differentiation, and repair

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