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DUSP4 regulates input to the suprachiasmatic circadian network via VIP-induced activation of the ERK1/2 pathway

ABSTRACT: DUSP4 regulates input to the suprachiasmatic circadian network via VIP-induced activation of the ERK1/2 pathway

PROVIDER: PRJNA454006 | ENA |

REPOSITORIES: ENA

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DUSP4 regulates input to the suprachiasmatic circadian network via VIP-induced activation of the ERK1/2 pathway

Project description:Analysis of the genes and cellular signalling cascades mediating the response of SCN slices to vasoactive intestinal peptide (VIP). Primary goal was to find novel genes that may be involved in circadian phase shifting for further study. Promoter analysis of significantly regulated genes and gene ontology analysis would provide information into pathways VIP acts through in the SCN.

2019-02-07 | GSE113797 | GEO

DUSP4 silencing

Project description:DUSP4 silencing

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NPAS4 regulates the transcriptional response of suprachiasmatic nucleus neurons to photic input

Project description:In mammals, the hypothalamic suprachiasmatic nucleus (SCN) is the master circadian pacemaker. It is primarily entrained by environmental photic stimuli. However, the molecular bases of the response of heterogeneous cells in the SCN to photic stimuli is not fully understood. In this study, we combined bulk RNA/ChIP/single nuclei sequencing with circadian behavioral assays to investigate cellular identities in the SCN and explore how they react to photic stimuli. We identified 3 major peptidergic cells in the SCN, Avp-expressing, Vip-expressing and Cck-expressing cells. In each peptidergic cell type, there is a light responsive cell cluster, and each of these is enriched for Neuronal PAS Domain Protein 4 (NPAS4) target genes. In addition, Npas4 null mice have a 1hr longer circadian period in constant darkness and a damped phase responsive curve to photic stimuli. Bulk RNA seq in Npas4-/- SCN revealed a reduced magnitude of light induced gene expression. Together, our data indicate that NPAS4 is part of the machinery that orchestrates the molecular response to photic stimuli in the SCN.

2021-08-23 | GSE148252 | GEO

NPAS4 regulates the transcriptional response of suprachiasmatic nucleus neurons to photic input

Project description:NPAS4 regulates the transcriptional response of suprachiasmatic nucleus neurons to photic input

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Vasoactive intestinal peptide controls the suprachiasmatic circadian clock network via ERK1/2 and DUSP4 signalling.

Project description:The suprachiasmatic nucleus (SCN) co-ordinates circadian behaviour and physiology in mammals. Its cell-autonomous circadian oscillations pivot around a well characterised transcriptional/translational feedback loop (TTFL), whilst the SCN circuit as a whole is synchronised to solar time by its retinorecipient cells that express and release vasoactive intestinal peptide (VIP). The cell-autonomous and circuit-level mechanisms whereby VIP synchronises the SCN are poorly understood. We show that SCN slices in organotypic culture demonstrate rapid and sustained circuit-level circadian responses to VIP that are mediated at a cell-autonomous level. This is accompanied by changes across a broad transcriptional network and by significant VIP-directed plasticity in the internal phasing of the cell-autonomous TTFL. Signalling via ERK1/2 and tuning by its negative regulator DUSP4 are critical elements of the VIP-directed circadian re-programming. In summary, we provide detailed mechanistic insight into VIP signal transduction in the SCN at the level of genes, cells and neural circuit.

| S-EPMC6358603 | biostudies-literature

DUSP4 silencing

Project description:siRNA mediated DUSP4 silencing in a cell line derived from a) AKT/NRAS double injected hepatocellular carcinoma in a mouse by hydrodynamic injection => AKT/NRAS and b) these cell lines with Cre knockout for AKT => AKT/NRAS Cre

2022-11-06 | GSE217233 | GEO

Spatiotemporal single-cell analysis of gene expression in the mouse suprachiasmatic nucleus

Project description:Mammalian circadian behaviors are orchestrated by suprachiasmatic nucleus (SCN) in the hypothalamus. Yet basic SCN cell types and their roles in circadian pacemaking are still unclear. In this study, we comprehensively characterized the basic cell types of SCN and their circadian and light-induced gene expression. In SCN, we identified seven major cell types among which neurons, astrocytes, ependymocytes and endothelial cells display cell-type specific circadian gene expression. We found that five SCN neuron subtypes, Avp+/Nms+, Vip+/Nms+, Vip+/Grp+, Cck+/C1ql3+ and Cck+/Bdnf+, differ in their spatial distribution, circadian rhythmicity and light responsiveness. Among the rhythmic neuron subtypes, we observed a wave of circadian gene expression propagating from the subtypes in posterior SCN to the subtypes in anterior SCN. Such wave can be explained by the neuropeptide-receptor signaling network in which Avp+/Nms+ subtype is the leader of circadian oscillations. Our study provides insights into the basic neural mechanism of circadian pacemaking in mammals.

2019-06-19 | GSE132608 | GEO

Spatiotemporal single-cell analysis of gene expression in the mouse suprachiasmatic nucleus

2019-06-19 | GSE117295 | GEO

Identification of genes regulated by DUSP4

Project description:In this study, we compared expression profiles between colorectal cancer cell line HCT116 with and without DUSP4 knockdown.

2021-03-23 | GSE145511 | GEO

Suprachiasmatic VIP neurons are required for normal circadian rhythmicity with a subset expressing a molecularly distinct pacemaker profile

Project description:Suprachiasmatic VIP neurons are required for normal circadian rhythmicity with a subset expressing a molecularly distinct pacemaker profile

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