This SuperSeries is composed of the SubSeries listed below.
Mapping gene regulatory circuitry of Pax6 during neurogenesis.
Specimen part
View SamplesPax6 is a highly conserved transcription factor among vertebrates and is important in various aspects of the central nervous system (CNS) development. However, the gene regulatory circuitry of Pax6 underlying these functions remains elusive. We find that, following expression in neural progenitor cells, Pax6 targets many promoters embedded in an active chromatin environment. Intriguingly, many of these sites are also bound by another progenitor factor, Sox2, which cooperates with Pax6 in gene regulation. A combinatorial analysis of Pax6 binding dataset with transcriptome changes in Pax6-deficient neural progenitors reveals a dual role for Pax6, in which it activates the neuronal (ectodermal) genes while concurrently represses the mesodermal and endodermal genes thereby ensuring the unidirectionality of lineage commitment towards glutamatergic neuronal differentiation. Furthermore, Pax6 is critical for inducing activity of transcription factors that elicit neurogenesis and repress others that promote non-neuronal lineages. In addition to many established downstream effectors, Pax6 directly binds and activates a number of genes that are specifically expressed in neural progenitors but have not been previously implicated in neurogenesis. The in utero knockdown of one such gene, Ift74, during brain development impairs polarity and migration of new-born neurons. These findings demonstrate new aspects of the gene regulatory circuitry of Pax6, revealing how it functions to control neuronal development at multiple levels to ensure unidirectionality and proper execution of the neurogenic program.
Mapping gene regulatory circuitry of Pax6 during neurogenesis.
Specimen part
View SamplesRapid nerve conduction in the CNS is facilitated by the insulation of axons with myelin, a specialized oligodendroglial compartment distant from the cell body. Myelin is turned over and adapted throughout life; however, the molecular and cellular basis of myelin dynamics is not well understood. Hypothesizing that only a fraction of all myelin-related mRNAs has been identified so far, we subjected myelin biochemically purified from mouse brains at various ages to RNA sequencing. We find a surprisingly large pool of transcripts abundant and/or enriched in myelin. Furthermore, a comprehensive analysis showed that the myelin transcriptome is closely related to the myelin proteome but clearly distinct from the transcriptomes of oligodendrocytes and brain tissues, suggesting that the incorporation of mRNAs into the myelin compartment is highly selective. The mRNA-pool in myelin displays maturation-dependent dynamic changes of composition, abundance, and functional associations; however ageing-dependent changes after 6 months of age were minor. We suggest that this transcript pool provides a basis for the local modulation of myelin turnover and adaptation, i.e. in the individual internode. Overall design: A light-weight membrane fraction enriched for myelin was purified from mouse brains as described previously (Jahn et al., Neuromethods, 2013). For RNA-Seq, RNA was isolated from myelin of mice from indicated ages.
The transcriptome of mouse central nervous system myelin.
Specimen part, Subject
View SamplesZebrafish (Danio rerio) gutGFP transgenic embryos [Tg(XlEef1a1:GFP)s854] were collected at 4 time points: 2 days post fertilization (dpf), 3, dpf, 4 dpf, 6 dpf. Embryos were dissociated into single cells and sorted by FACS based on GFP expression.
FACS-assisted microarray profiling implicates novel genes and pathways in zebrafish gastrointestinal tract development.
Age
View SamplesTo identify genes expressed in specific developing thalamic nuclei during embryonic stages, a genetic dual labelling strategy was established to mark and isolate the cells. Transcription profiles were determined for the principal sensory thalamic populations by genome-wide analysis.
Genetic Labeling of Nuclei-Specific Thalamocortical Neurons Reveals Putative Sensory-Modality Specific Genes.
Specimen part
View SamplesMisguided visual thalamic axons leads to changes in gene expression in visual thalamic neurons.
Genetic Labeling of Nuclei-Specific Thalamocortical Neurons Reveals Putative Sensory-Modality Specific Genes.
Specimen part
View Samplescdipt is an essential gene in the synthesis of phosphatidylinositol (PtdIns) in the zebrafish, Danio rerio. The zebrafish mutant cdipt^hi559Tg (ZL782) carries a retroviral insertion which inactivates cdipt. Homozygous mutants exhibit hepatocellular endoplasmic reticulum (ER) stress and non-alcoholic fatty liver disease (NAFLD) pathologies at 5 days post fertilization (dpf). This study reveals a novel link between PtdIns, ER stress, and steatosis.
Lack of de novo phosphatidylinositol synthesis leads to endoplasmic reticulum stress and hepatic steatosis in cdipt-deficient zebrafish.
Age
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Target genes of Topoisomerase IIβ regulate neuronal survival and are defined by their chromatin state.
Specimen part, Treatment
View SamplesExpression profiling of from Top2 knokout and ICRF-193 treated neurons reveals a significant number of genes that are transcriptionally deregulated
Target genes of Topoisomerase IIβ regulate neuronal survival and are defined by their chromatin state.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Depletion of DNMT1 in differentiated human cells highlights key classes of sensitive genes and an interplay with polycomb repression.
Sex, Specimen part, Time
View Samples