ABSTRACT: Whole genome bisulfite sequencing of mouse neural progenitor cells and neurons from the mouse cerebral cortex at day 15.5 of embryonic development
Project description:Tissue-specific deletion of the gene encoding the histone acetyltransferase Kat7 (Hbo1) in the developing mouse central nervous system using cre-recombinase expression driven by regulatory sequences of the nestin locus (NesCre transgene) resulted in defective cerebral cortex development, a complete failure of neural stem cells to give rise to neurons and oligodendrocytes during in vitro differentiation, and a failure to express the neuronal differentiation program. Proliferating neural stem and progenitor cells (NPSCs) were isolated from Kat7-deleted and Kat7-intact 14.5 day embryonic mouse fetuses.
Project description:The cerebral cortex plays an important role in cognitive function and specialized perception in mammals and its development requires highly specific spatio-temporal control of gene expression. The study identified stage- and region-specific markers throughout cerebral corticogenesis at various important stages of cerebral cortex development; embryonic day (E) 15.5, E17.5, postnatal day (P) 1.5 and 4-6 months old. The study involved the analysis of 12 SAGE libraries, which were generated from the mouse cerebral cortex of E15.5 (n=3), E17.5 (n=2), P1.5 (n=1) and 4-6 month old (n=6). N denotes biological replicates.
Project description:Whole genome bisulfite-seq on embryonic 15.5 day mouse neural tube For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
Project description:The cerebral cortex plays an important role in cognitive function and specialized perception in mammals and its development requires highly specific spatio-temporal control of gene expression. The study identified stage- and region-specific markers throughout cerebral corticogenesis at various important stages of cerebral cortex development; embryonic day (E) 15.5, E17.5, postnatal day (P) 1.5 and 4-6 months old.
Project description:Neurosphere cultures prepared from E14.5 mouse cerebral cortex at passage 3 were treated for 4 hours with 100 nM dexamethasone We used microarrays to detail the global program of dexamethasone regulated gene expression in embryonic neural progenitor/stem cells. Cerebral cortex was isolated from E14.5 mouse fetuses and cultured as neurospheres for 3 passages prior to treatment with 100 nM dexamethasone or ethanol vehicle for 4 hours.
Project description:Neurosphere cultures prepared from E14.5 mouse cerebral cortex at passage 3 were treated for 4 hours with 100 nM dexamethasone We used microarrays to detail the global program of dexamethasone regulated gene expression in embryonic neural progenitor/stem cells
Project description:During embryonic development, the cerebral cortex is equipped with excitatory projection and inhibitory interneurons that migrate in organized layers. Periventricular heterotopia (PH) is a rare and heterogeneous disorder in which a subpopulation of new-born projection neurons fails to initiate their radial migration to the cortex, ultimately resulting in bands or nodules of grey matter lining the lateral ventricles underneath a normal cortex. For many years, few genes had been identified that cause this disorder upon disruption, but recently it was shown that PH is genetically a very heterogeneous disease. Here, we study the neurodevelopmental role of endothelin converting enzyme 2 (ECE2), biallelic mutations in which have been identified in two patients with PH. Our results show that manipulation of ECE2 levels or activity in human cerebral organoids and in the developing mouse cortex leads to ectopic localization of neural progenitors and neurons. We uncover the role of ECE2 in neurogenesis and, mechanistically, we identify its involvement in generation and secretion of extracellular matrix and in protein phosphorylation. This strongly suggests ECE2 as a novel candidate gene for PH.
Project description:GABAergic interneurons play crucial roles in the regulation of neural circuit activity in the cerebral cortex. A hallmark of cortical interneurons is their remarkable structural and functional diversity, yet the molecular determinants and the precise timing underlying their diversification remain largely unknown. Here we use single-cell transcriptomics to identify distinct types of progenitor cells and newborn neurons in the ganglionic eminences, the embryonic proliferative regions that give rise to cortical interneurons. These embryonic precursors define temporally and spatially restricted transcriptional trajectories that unambiguously relate to specific classes of interneurons in the adult cerebral cortex. Our findings therefore suggest that interneuron diversity is already patent shortly after neurons become postmitotic through the acquisition of specific transcriptional programs that unfold over several weeks in the developing cortex
Project description:<p>Non-coding regions comprise most of the human genome and harbor a significant fraction of risk alleles for neuropsychiatric diseases, yet their functions remain poorly defined. We created a high-resolution map of non-coding elements involved in human cortical neurogenesis by contrasting chromatin accessibility and gene expression in the germinal zone and cortical plate of the developing cerebral cortex. To obtain a high resolution depiction of chromatin structure and gene expression in developing human fetal cortex, we dissected the post-conception week (PCW) 15-17 human neocortex into two major anatomical divisions to distinguish between proliferating neural progenitors and post mitotic neurons: (1) GZ: the neural progenitor-enriched region encompassing the ventricular zone (VZ), subventricular zone (SVZ), and intermediate zone (IZ) and (2) CP: the neuron-enriched region containing the subplate (SP), cortical plate (CP), and marginal zone (MZ). Tissues were obtained from three independent donors and three to four technical replicates from each tissue were processed for ATAC-seq to define the landscape of accessible chromatin and RNA-seq for genome-wide gene expression profiling.</p>
Project description:TBR1 is a forebrain specific T-box transcription factor. Tbr1-/- mice have been characterized by defective axonal projections from cerebral cortex and abnormal neuronal migration of cerebral cortex and amygdala. To investigate how TBR1 regulates neural development, the gene expression profile of Tbr1-/- brains was compared with WT littermates. Total RNAs purified from forebrains at embryonic day 16.5 were hybridized on Affymetrix microarrays