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Spatial enhancer activation influences inhibitory neuron identity during mouse embryonic development

ABSTRACT: Spatial enhancer activation influences inhibitory neuron identity during mouse embryonic development

PROVIDER: PRJNA967670 | ENA |

REPOSITORIES: ENA

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Spatial enhancer activation influences inhibitory neuron identity during mouse embryonic development

Project description:Spatial enhancer activation influences inhibitory neuron identity during mouse embryonic development

| PRJNA967667 | ENA

Spatial enhancer activation determines inhibitory neuron identity (ChIP-seq of MEIS transcription factors)

Project description:Spatial enhancer activation determines inhibitory neuron identity (ChIP-seq of MEIS transcription factors)

| PRJNA967672 | ENA

Spatial enhancer activation influences inhibitory neuron identity during mouse embryonic development

Project description:The mammalian telencephalon contains distinct GABAergic projection neuron and interneuron types, originating in the germinal zone of the embryonic basal ganglia. How genetic information in the germinal zone determines cell types is unclear. Here we use a combination of in vivo CRISPR perturbation, lineage tracing and ChIP-sequencing analyses and show that the transcription factor MEIS2 favors the development of projection neurons by binding enhancer regions in projection-neuron-specific genes during mouse embryonic development. MEIS2 requires the presence of the homeodomain transcription factor DLX5 to direct its functional activity toward the appropriate binding sites. In interneuron precursors, the transcription factor LHX6 represses the MEIS2-DLX5-dependent activation of projection-neuron-specific enhancers. Mutations of Meis2 result in decreased activation of regulatory enhancers, affecting GABAergic differentiation. We propose a differential binding model where the binding of transcription factors at cis-regulatory elements determines differential gene expression programs regulating cell fate specification in the mouse ganglionic eminence.

2024-02-19 | GSE231774 | GEO

Spatial enhancer activation determines inhibitory neuron identity (ChIP-seq of MEIS transcription factors)

Project description:The mammalian telencephalon contains a tremendous diversity of GABAergic projection neuron and interneuron types, that originate in a germinal zone of the embryonic basal ganglia. How genetic information in this transient structure is transformed into different cell types is not yet fully understood. Using a combination of in vivo lineage tracing, CRISPR perturbation and ChIP-seq in mice, we found that the transcription factor MEIS2 favors the development of projection neurons through genomic binding sites in regulatory enhancers of projection neuron specific genes. MEIS2 requires the presence of the homeodomain transcription factor DLX5 to direct its functional activity towards these sites. In interneurons, the activation of projection neuron specific enhancers by MEIS2 and DLX5 is repressed by the transcription factor LHX6. When MEIS2 carries a mutation associated with intellectual disability in humans, it is less effective at activating enhancers involved in projection neuron development. This suggests that GABAergic differentiation may be impaired in patients carrying this mutation. Our research has uncovered a mechanism by which the selective activation of enhancers plays a crucial role in the establishment of neuronal identity, as well as in potential pathological mechanisms

2024-02-19 | GSE231777 | GEO

Spatial enhancer activation influences inhibitory neuron identity during mouse embryonic development

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-02-19 | GSE231779 | GEO

Tissue architecture influences brain organoid identity and developmental trajectory

Project description:This project used snRNA-seq and Molecular Cartography (single cell spatial transcriptomics) to investigate the relation between morphology and molecular identity in human brain organoids.

2022-09-16 | E-MTAB-11564 | biostudies-arrayexpress

Tissue architecture influences brain organoid identity and developmental trajectory

Project description:Tissue architecture influences brain organoid identity and developmental trajectory

| PRJEB51969 | ENA

The imbalance of excitatory/inhibitory neuron differentiation in neurodevelopmental disorders with an NR2F1 point mutation

Project description:Recent studies have revealed an essential role for embryonic cortical development in the pathophysiology of neurodevelopmental disorders, including autism spectrum disorder (ASD). However, the genetic basis and underlying mechanisms remain unclear. Here, we generate mutant human embryonic stem cell lines (Mut hESCs) carrying an NR2F1-R112K mutation that has been identified in a patient with ASD features, and investigate their neurodevelopmental alterations. Mut hESCs overproduce ventral telencephalic neuron progenitors (ventral NPCs) and inhibitory neurons, and underproduce dorsal NPCs and excitatory neurons. These alterations can be mainly attributed to the aberrantly activated Hedgehog signaling pathway. Moreover, the corresponding Nr2f1 point mutant mice display a similar excitatory/inhibitory neuron imbalance and abnormal behaviors. Antagonizing the increased inhibitory synaptic transmission partially alleviates their behavioral deficits. Together, our results suggest that the NR2F1-dependent imbalance of excitatory/inhibitory neuron differentiation caused by the activated Hedgehog pathway is one precursor of neurodevelopmental disorders and may enlighten the therapeutic approaches.

2020-04-21 | GSE132965 | GEO

Ptf1a promotes an inhibitory peptidergic identity in cortical pyramidal cells in vivo

Project description:Ptf1a has been shown to be necessary for determining an inhibitory interneuronal fate in many regions of the nervous system. In this study, we aim to investigate the sufficiency of Ptf1a to cell-autonomously promote a specific neuronal identity by misexpressing it in developing excitatory cortical pyramidal cells and studying its impact on pyramidal cell features, such as its gene expression profile. To accomplish this, we electroporate either a Ptf1a/GFP-misexpression construct or a GFP-only control construct into E12.5 mouse embryonic cortices, harvest the cortices at E15.5, and examine Ptf1a-induced changes to the pyramidal cell transcriptome, molecular expression pattern, neurotransmitter status, and morphology. We conclude that Ptf1a is sufficient to cell-autonomously promote an inhibitory peptidergic identity and alter neuronal morphology in developing cortical pyramidal cells. The results of this study provide insight into intrinsic transcriptional controls over neuronal identity, specifically implicate Ptf1a as a potent regulator of an inhibitory peptidergic identity, and may guide future studies of neuronal reprogramming for circuit repair after disease or injury.

2015-03-20 | GSE59481 | GEO

The imbalance of excitatory/inhibitory neuron differentiation in neurodevelopmental disorders with an NR2F1 point mutation (The Third Replicate)

2023-04-07 | GSE141468 | GEO