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Tbr2 and Neurog2 occupancy and transcriptional profiling of control and Tbr2 knockout E14.5 cerebral cortices

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE63621 | GEO | 2016/09/08

SECONDARY ACCESSION(S): PRJNA268481

REPOSITORIES: GEO

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Tbr2 and Neurog2 occupancy and transcriptional profiling of control and Tbr2 knockout E14.5 cerebral cortices

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-09-08 | E-GEOD-63621 | biostudies-arrayexpress

Tbr2 and Neurog2 occupancy and transcriptional profiling of control and Tbr2 knockout E14.5 cerebral cortices

Project description:Tbr2 and Neurog2 occupancy and transcriptional profiling of control and Tbr2 knockout E14.5 cerebral cortices

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Tbr2 and Neurog2 transcription factor binding sites in E14.5 WT cerebral cortices

Project description:To date, speculations on the molecular roles of Tbr2 transcription factor during specification, maintenance and differentiation of cortical specific Intermediate Neural Progenitors are coming from the analysis of loss- and gain-of-function experiments. However since its capacity to bind the DNA to extert its function we did Chromatin Immuno-Precipitation followed by deep sequencing to profile its target on the genome. We performed this approach directly in vivo to respect the physiological and peculiar enviroment of its action during cortical development. Moreover we did the same approach for Neurogenin 2 proneural gene. Interestingly the vast majority of the Neurog2 peaks are in common with Tbr2 dataset suggesting a co-operation between the two factors confirmed by biochemical and functional assays. Finally we compared Tbr2 dataset with the DNA regions bound by the H3K27me3 histone demethylase Jmjd3 (NCBI:Kdm6b) obtained by others. Interestingly we were able to find regions in common linked to important genes for neuronal differentiation.

2016-09-08 | GSE63620 | GEO

Tbr2 and Neurog2 transcription factor binding sites in E14.5 WT cerebral cortices

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Transcriptional profiling of E14.5 control and Tbr2 fl/fl;Foxg1::Cre cortices

Project description:The abscence of TBR2 gene in human leads to microcephaly. This condition is mimicked by the specific ablation of the murine gene in developing cerebral cortex. Herein we compared gene expression in control and Tbr2 cKO in E14.5 cerebral cortices. This approach represents a useful tool to identify the molecular mechanisms at the basis of the phenotype.

2016-09-08 | GSE63619 | GEO

Transcriptional profiling of E14.5 control and Tbr2 fl/fl;Foxg1::Cre cortices

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Gene expression in basal progenitors in the cerebral cortex of Tbr2 conditional knockout mice

Project description:During cortical development neurons are generated from basal progenitors (BPs) which specifically express the transcription factor Tbr2. We used fluorescent-activated cell sorting (FACS) to isolate BPs from Tbr2-conditional knockout mice brain at early (E13) and late (E16) stages of cortical neurogenesis and determined mRNA expression profiles using microarray (Illumina MouseWG-6 v2). Role of transcription factor Tbr2 in basal progenitors during corticogenesis.

2019-10-12 | GSE121180 | GEO

Multimodal profiling of the transcriptional regulatory landscape of the developing mouse cortex identifies Neurog2 as a key epigenome remodeler.

Project description:How multiple epigenetic layers and transcription factors (TFs) interact to facilitate brain development is largely unknown. Here, to systematically map the regulatory landscape of neural differentiation in the mouse neocortex, we profiled gene expression and chromatin accessibility in single cells and integrated these data with measurements of enhancer activity, DNA methylation and three-dimensional genome architecture in purified cell populations. This allowed us to identify thousands of new enhancers, their predicted target genes and the temporal relationships between enhancer activation, epigenome remodeling and gene expression. We characterize specific neuronal transcription factors associated with extensive and frequently coordinated changes across multiple epigenetic modalities. In addition, we functionally demonstrate a new role for Neurog2 in directly mediating enhancer activity, DNA demethylation, increasing chromatin accessibility and facilitating chromatin looping in vivo. Our work provides a global view of the gene regulatory logic of lineage specification in the cerebral cortex.

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Prenatal ?-catenin/Brn2/Tbr2 transcriptional cascade regulates adult social and stereotypic behaviors.

Project description:Social interaction is a fundamental behavior in all animal species, but the developmental timing of the social neural circuit formation and the cellular and molecular mechanisms governing its formation are poorly understood. We generated a mouse model with mutations in two Disheveled genes, Dvl1 and Dvl3, that displays adult social and repetitive behavioral abnormalities associated with transient embryonic brain enlargement during deep layer cortical neuron formation. These phenotypes were mediated by the embryonic expansion of basal neural progenitor cells (NPCs) via deregulation of a ?-catenin/Brn2/Tbr2 transcriptional cascade. Transient pharmacological activation of the canonical Wnt pathway during this period of early corticogenesis rescued the ?-catenin/Brn2/Tbr2 transcriptional cascade and the embryonic brain phenotypes. Remarkably, this embryonic treatment prevented adult behavioral deficits and partially rescued abnormal brain structure in Dvl mutant mice. Our findings define a mechanism that links fetal brain development and adult behavior, demonstrating a fetal origin for social and repetitive behavior deficits seen in disorders such as autism.

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Gene expression in Tbr2 lineage neurons in the murine cerebral cortex

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2019-10-18 | GSE121470 | GEO

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