Nr4a1 regulates cell-specific transcriptional programs in inhibitory GABAergic interneurons
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ABSTRACT:
PROVIDER: PRJNA1095557 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28536400_1.fastq.gz | Fastqsanger.gz | |||
| SRR28536400_2.fastq.gz | Fastqsanger.gz | |||
| SRR28536401_1.fastq.gz | Fastqsanger.gz | |||
| SRR28536401_2.fastq.gz | Fastqsanger.gz | |||
| SRR28536402_1.fastq.gz | Fastqsanger.gz |
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Project description:The patterns of synaptic connectivity and physiological properties of diverse neuron types are shaped by distinct gene sets. Our study demonstrates that, in the mouse forebrain, the transcriptional profiles of inhibitory GABAergic interneurons are regulated by Nr4a1, an orphan nuclear receptor whose expression is transiently induced by sensory experiences and is required for normal learning. Nr4a1 exerts contrasting effects on the local axonal wiring of Parvalbumin- and Somatostatin-positive interneurons, which innervate different subcellular domains of their postsynaptic partners. The loss of Nr4a1 activity in these interneurons results in bidirectional, cell-type-specific transcriptional switches across multiple gene families, including those involved in surface adhesion and repulsion. Our findings reveal that combinatorial synaptic organizing codes are surprisingly flexible and highlight a mechanism by which inducible transcription factors can influence neural circuit structure and function.
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Project description:Our research is to investigate the role of Brpf1 in the development and function of GABAergic interneurons. To test this, we used mouse primary in vitro cultured GABAergic interneurons derived from medial ganglionic eminence (MGE) and utilized AAV-shBrpf1 virus to knockdown Brpf1. We performed mRNA-seq on the total RNA extracted from the infected neurons .We found that most of the up-regulated genes after Brpf1 knockdown were involved in processes such as protein binding, gene negative transcription, ubiquitination, and inflammation by mRNA-seq. We found that many genes related to neuronal calcium, potassium ion transport and neurotransmitter release changed after Brpf1 was knockdown.Our results demonstrate the key role of Brpf1 in related gene expression of GABAergic interneurons, and provide new lights on the underlying neurobiological mechanisms of BRPF1 mutations that cause mental retardation in children or adolescents.
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Project description:During embryonic development, GABAergic interneurons, a main inhibitory component in the cerebral cortex, migrate tangentially from the ganglionic eminence (GE) to cerebral cortex. After reaching the cerebral cortex, they start to extend their neurites for constructing local neuronal circuits around the neonatal stage. Aberrations in migration or neurite outgrowth are implicated in neurological and psychiatric disorders such as epilepsy, schizophrenia and autism. Previous studies revealed that in the early phase of cortical development the neural population migrates tangentially from the GE in the telencephalon and several genes have been characterized as regulators of migration and specification of GABAergic interneurons. However, much less is known about the molecular mechanisms of GABAergic interneurons-specific maturation at later stages of development. Here, we performed genome-wide screening to identify genes related to the later stage by flow cytometry based-microarray (FACS-array) and identified 247 genes expressed in cortical GABAergic interneurons. Among them, Dgkg, a member of diacylglycerol kinase family, was further analyzed. Correlational analysis revealed that Dgkg is dominantly expressed in somatostatin (SST)-expressing GABAergic interneurons. The functional study of Dgkg using GE neurons indicated alteration in neurite outgrowth of GABAergic neurons. This study shows a new functional role for Dgkg in GABAergic interneurons as well as the identification of other candidate genes for their maturation.
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