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Next Generation Sequencing analysis of Lhx6 heterozygote and null forebrain transcriptomes at post natal day 15

ABSTRACT: Here we characterize the changes in the forebrain transcriptome resulting from the deletion of the transcription factor Lhx6, generated by RNA-seq technology with biologic replication. Lhx6 is an essential regulatory gene in the development of cortical interneurons generated in the medial ganglionic eminences of the embryonic brain. This data contains insights into gene networks important for the development of medial ganglionic eminence derived interneurons.

ORGANISM(S): Mus musculus

PROVIDER: GSE108161 | GEO | 2017/12/16

SECONDARY ACCESSION(S): PRJNA422615

REPOSITORIES: GEO

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Comparison of gene expression signature between nascent Lhx6-GFP+ cells from mouse embryonic brain and differentiated Lhx6-GFP+ cells from ES cells (as well as comparing those of Lhx6-GFP+ and Lhx6-GFP- cells from ES cells)

2013-01-16 | GSE43508 | GEO

Project description:There was a remarkable similarity in the molecular properties of the MGE-GFP+ and ES-GFP+ cells. In particular, genes that are important for medial ganglionic eminence (MGE) and cortical interneurons development are both high in expression in both MGE-Lhx6-GFP+ and ES-Lhx6-GFP+ cells (compared to ES-Lhx6-GFP- cells). To investigate how closely ES cells-derived Lhx6-GFP+ cells resembled authentic Lhx6+ MGE cells, and to define the molecular properties of the Lhx6-GFP+ and Lhx6-GFP- cells from differentiated ES cells, we compared their gene expression profiles. We used FACS to purify GFP+ cells from the E12.5 MGE of Lhx6-GFP transgenic mice. ES-Lhx6-GFP+ cells and ES-Lhx6-GFP- cells (both from D12 EB aggregates) were also isolated by fluorescent activated cell sorting (FACS) and all of the RNA samples were subjected to RNA expression microarray analyses.

2013-01-16 | E-GEOD-43508 | biostudies-arrayexpress

Bulk RNA-seq of the human fetal neocortex, lateral ganglionic eminence and medial ganglionic eminence at 7, 9, 11 and 20 post-conceptional weeks

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Sp9 regulates medial ganglionic eminence-derived cortical interneuron development

Project description:In the mammalian cortex, about 60% of GABAergic interneurons, mainly including parvalbumin-expressing (PV+) and somatostatin (SST+) interneurons are generated from the medial ganglionic eminence (MGE) in the subpallium and tangentially migrate to the cortex. Here we analyze the role of the Sp9 transcription factor in regulating the development of MGE-derived cortical interneurons. We show that SP9 is widely expressed in the MGE subventricular zone (SVZ) and in MGE-derived migrating interneurons. By analyzing Sp9 null and conditional mutant mice, we demonstrate that Sp9 promotes MGE progenitor proliferation in the SVZ and is required for the normal patterning of tangential migration and the laminar distribution of MGE-derived cortical GABAergic interneurons. Loss of Sp9 function results in a ~50% reduction of MGE-derived cortical interneurons, an ectopic aggregation of MGE-derived neurons in the embryonic ventral telencephalon, and an increased ratio of SST+/PV+ cortical interneurons. Finally, we provide evidence that Sp9 regulates MGE derived cortical interneuron development through promoting expression of the Lhx6 and Lhx8 transcription factors.

2017-05-19 | GSE99049 | GEO

Assessment of gene expression changes during human cortical interneuron development

Project description:We have used our protocol for generating cortical interneurons from human embryonic stem cells (hESCs) to study gene expression changes during this process, to identify regulatory networks critical to cortical interneuron development. Samples were collected at day 0 (hESCs), day 15 (ventral telencephalic patterned medial ganglionic eminence-like progenitors), day 35 (immature interneurons), and day 60 (mature interneurons).

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Transcriptional Networks Controlled by NKX2-1 in the Development of Forebrain GABAergic Neurons (ChIP-Seq)

Project description:The embryonic basal ganglia generates multiple projection neurons and interneuron subtypes from distinct progenitor domains. Combinatorial interactions of transcription factors (TFs), regulatory elements (REs), and chromatin are thought to precisely regulate gene expression. In the medial ganglionic eminence (MGE), the NKX2-1 TF controls regional identity and, with LHX6, is necessary to specify pallidal projection neurons and forebrain interneurons. We dissected the molecular functions of NKX2-1 by defining its chromosomal binding regions, regulation of gene expression and epigenetic state. NKX2-1 binding at distal REs led to a repressed epigenetic state and transcriptional repression in the ventricular zone. Conversely, Nkx2-1 is required to establish a permissive chromatin state and transcriptional activation in the sub- ventricular and mantle zones. Moreover, combinatorial binding of NKX2-1 and LHX6 promotes transcriptionally permissive chromatin and activates genes expressed in cortical migrating interneurons. Our integrated approach provides a foundation for elucidating transcriptional networks guiding the development of the MGE and its descendants.

2016-09-21 | GSE85704 | GEO

Transcriptional Networks Controlled by NKX2-1 in the Development of Forebrain GABAergic Neurons (microarray)

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Comparative expression of embryonic medial- and lateral/caudal-ganglionic eminence cells migrating in the mouse cerebral cortex

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2022-08-21 | GSE207506 | GEO

Sonic hedgehog Activation Restores Interneurons and Cognitive Function in Newborns with Intraventricular Hemorrhage

Project description:We hypothesized that the occurrence of IVH would reduce interneuron neurogenesis in the medial ganglionic eminence and diminish the population of parvalbumin+ and somatostatin+ cortical interneurons. Since Sonic Hedgehog promotes the production of cortical interneurons, we also postulated that the activation of Sonic Hedgehog signaling might restore neurogenesis, cortical interneuron population, and neurobehavioral function in premature newborns with IVH.

2022-08-06 | GSE210477 | GEO

Expression data from purified medial ganglionic eminence (MGE) interneurons, 3 biological replicates

Project description:During development, newborn interneurons migrate throughout the embryonic brain. Here, we provide evidence that these interneurons act in a paracrine fashion to regulate developmental oligodendrocyte formation. Specifically, we show that medial ganglionic eminence (MGE) interneurons secrete factors that promote genesis of oligodendrocytes from glially-biased cortical precursors in culture. Moreover, when MGE interneurons are genetically ablated in vivo prior to their migration, this causes a deficit in cortical oligodendrogenesis. Modeling of the interneuron-precursor paracrine interaction using transcriptome data identifies the cytokine fractalkine as responsible for the pro-oligodendrocyte effect in culture. This paracrine interaction is important in vivo, since knockdown of the fractalkine receptor CX3CR1 in embryonic cortical precursors, or constitutive knockout of CX3CR1 causes decreased numbers of oligodendrocyte progenitor cells (OPCs) and oligodendrocytes in the postnatal cortex. Thus, in addition to their role in regulating neuronal excitability, interneurons act in a paracrine fashion to promote the developmental genesis of oligodendrocytes. We used microarrays to generate a list of expressed genes in purified medial ganglionic eminence (MGE) interneurons

2017-03-06 | GSE95696 | GEO

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