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Activity-induced MeCP2 phosphorylation regulates retinogeniculate synapse refinement [snRNA-Seq]

ABSTRACT: Activity-induced MeCP2 phosphorylation regulates retinogeniculate synapse refinement [snRNA-Seq]

PROVIDER: PRJNA1026637 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26340590_1.fastq.gz	Fastqsanger.gz
	SRR26340590_2.fastq.gz	Fastqsanger.gz
	SRR26340591_1.fastq.gz	Fastqsanger.gz
	SRR26340591_2.fastq.gz	Fastqsanger.gz
	SRR26340592_1.fastq.gz	Fastqsanger.gz

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Activity-induced MeCP2 phosphorylation regulates retinogeniculate synapse refinement [snRNA-Seq]

Project description:Mutations in MECP2 give rise to Rett syndrome (RTT), an X-linked neurodevelop- mental disorder that results in broad cognitive impairments in females. While the exact etiology of RTT symptoms remains unknown, one possible explanation for its clinical presentation is that loss of MeCP2 causes miswiring of neural circuits due to defects in the brain’s capacity to respond to changes in neuronal activity and sensory experience. Here, we show that MeCP2 is phosphorylated at four residues in the brain (S86, S274, T308, and S421) in response to neuronal activity, and we generate a quadruple knock-in (QKI) mouse line in which all four activity-dependent sites are mutated to alanines to prevent phosphorylation. QKI mice do not display overt RTT phenotypes or detectable gene expression changes in two brain regions. However, electrophysiological recordings from the retinogeniculate synapse of QKI mice reveal that while synapse elimination is initially normal at P14, it is significantly compromised at P20. Notably, this phenotype is distinct from the synapse refinement defect previously reported for Mecp2 null mice, where synapses initially refine but then regress after the third postnatal week. We thus propose a model in which activity-induced phosphorylation of MeCP2 is critical for the proper timing of retinogeniculate synapse maturation specifically during the early postnatal period.

2023-10-15 | GSE245024 | GEO

Activity-induced MeCP2 phosphorylation regulates retinogeniculate synapse refinement

Project description:Activity-induced MeCP2 phosphorylation regulates retinogeniculate synapse refinement

| PRJNA1026629 | ENA

Activity-induced MeCP2 phosphorylation regulates retinogeniculate synapse refinement [ChIP-Seq]

2023-10-15 | GSE245021 | GEO

Activity-induced MeCP2 phosphorylation regulates retinogeniculate synapse refinement [RNA-Seq]

2023-10-15 | GSE245022 | GEO

Activity-induced MeCP2 phosphorylation regulates retinogeniculate synapse refinement [RNA-Seq]

Project description:Activity-induced MeCP2 phosphorylation regulates retinogeniculate synapse refinement [RNA-Seq]

| PRJNA1026636 | ENA

Activity-induced MeCP2 phosphorylation regulates retinogeniculate synapse refinement [ChIP-Seq]

Project description:Activity-induced MeCP2 phosphorylation regulates retinogeniculate synapse refinement [ChIP-Seq]

| PRJNA1026635 | ENA

Activity-induced MeCP2 phosphorylation regulates retinogeniculate synapse refinement

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

2023-10-15 | GSE245026 | GEO

Visual experience-dependent expression of Fn14 is required for retinogeniculate refinement (development RNA-Seq)

Project description:Sensory experience influences the establishment of neural connectivity through molecular mechanisms that remain unclear. Here, we employ single-nucleus RNA-sequencing to investigate the contribution of sensory-driven gene expression to synaptic refinement in the dorsal lateral geniculate nucleus of the thalamus, a region of the brain that processes visual information. We find that visual experience induces the expression of the cytokine receptor Fn14 in excitatory thalamocortical neurons. By combining electrophysiological and structural techniques, we show that Fn14 is dispensable for early phases of refinement mediated by spontaneous activity, but that Fn14 is essential for refinement during a later, experience-dependent period of development. Refinement deficits in mice lacking Fn14 are associated with functionally weaker and structurally smaller retinogeniculate inputs, indicating that Fn14 mediates both functional and anatomical rearrangements in response to sensory experience. These findings identify Fn14 as a molecular link between sensory-driven gene expression and vision-sensitive refinement in the brain.

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Visual experience-dependent expression of Fn14 is required for retinogeniculate refinement (stimulus RNA-Seq)

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Visual experience-dependent expression of Fn14 is required for retinogeniculate refinement (Fn14 KO RNA-Seq)

2021-07-12 | GSE117023 | GEO