E-MTAB-9805
Ontology highlight
ABSTRACT:
PROVIDER: E-MTAB-9805 | ExpressionAtlas | 2020-12-09
REPOSITORIES: ExpressionAtlas
Similar Datasets
Project description:Stress and neuronal activity during a critical period regulate odorant receptor expression in Drosophila Melanogaster
| PRJEB41507 | ENA
Project description:Postmortem studies reveal increased density of synapses in brains of individuals with autism spectrum disorder (ASD. These observations have led to the hypothesis that defects in synaptic pruning may contribute to ASD pathology. Synaptic pruning, also called synaptic elimination or refinement, is a neuroplastic process involving the removal of ectopic synapses formed in the initial stages of neuronal development. Studies in vertebrates and invertebrates indicate that a crucial factor regulating synaptic pruning is neuronal activity, which was first hypothesized by Nobel laureates Hubel and Wiesel in the 1960s. Studies at the vertebrate retina as well as the mammalian and Drosophila neuromuscular junction (NMJ) indicate that waves of prenatal electrical activity and calcium (Ca2+) oscillations regulate the withdrawal of off-target synaptic contacts. Ca2+ oscillations regulate Ca2+-dependent molecular factors such as kinases (e.g. CaMKII), phosphatases (Calcineurin), and Ca2+-dependent adenylyl cyclases, which in turn regulate intracellular cyclic AMP (cAMP) levels for synaptic pruning in mammalian visual neurons and at the Drosophila NMJ21. Whereas a model to explain the refinement of synaptic connections often involves mechanisms based on Hebbian-like, spike-timing correlation between synaptic partners, where asynchronous inputs are removed, alternative non-Hebbian mechanisms have also been proposed that rely on activity-dependent modulation of chemorepulsion. Although some molecular aspects underlying activity-dependent synaptic refinement have recently been elucidated what molecules link dynamic levels of neuronal activity and the refinement of synaptic contacts during development remain to be elucidated. Consistent with its contributions to advance our understanding of synaptic development, Drosophila melanogaster has emerged as a suitable genetic model system for investigating fundamental mechanisms associated with ASD.
2025-10-06 | PXD061426 | Pride
Project description:During sensitive postnatal periods, brain neural circuits undergo significant refinement coincident with widespread neuronal alternative splicing events in which hundreds of genes alter their splice site selection to generate isoforms essential for synaptic plasticity. Here, we reveal that neuronal activity-dependent serine119 phosphorylation of paxillin (p-paxillin S119) acts as a molecular switch in the nucleus to modulate alternative splicing during this period. We report that following NMDA receptor activation, nuclear p-paxillin S119 is recruited to nuclear speckles, where it interacts with U2AFs and splicing factors. Neuronal paxillin expression is required for timely alternative splicing of synaptic factors, including Snap25. Consequently, young mice lacking paxillin S119 phosphorylation exhibit significantly reduced levels of Snap25-5b isoforms, impaired presynaptic function at hippocampal Schaffer collateral-CA1 synapses, and deficits in short-term learning and memory. These findings support the idea that nuclear p-paxillin S119 is a critical mediator of alternative splicing programs in postnatal neurons during a sensitive period essential for neural plasticity.
2025-08-08 | PXD060131 | Pride
Project description:In fasted mammals, glucose homeostasis is maintained through activation of the cAMP responsive CREB coactivator TORC2, which stimulates the gluconeogenic program in concert with the forkhead transcription factor FOXO1. Here we show that starvation also triggers TORC activation in Drosophila, where it maintains energy balance by promoting the expression of CREB target genes in the brain. TORC mutant flies have reduced glycogen and lipid stores, and they are sensitive to starvation as well as oxidative stress. Neuronal TORC expression rescued starvation and oxidative stress sensitivity as well as CREB target gene expression in TORC mutants. During refeeding, increases in insulin signaling inhibited TORC activity in wild type flies by stimulating the Salt Inducible Kinase 2 (SIK2)-mediated phosphorylation and subsequent degradation of TORC. Depletion of neuronal SIK2 increased TORC activity and enhanced resistance to starvation and oxidative stress in adult flies. As disruption of insulin signaling, either by ablation of insulin-producing cells (IPCs) or by mutation of the insulin receptor adaptor gene chico, also increased TORC activity, our results illustrate the importance of an insulin-regulated pathway in brain that promotes energy balance in Drosophila. Experiment Overall Design: Male fly heads were collected after 24h fasting, and RNA was extracted using RNAeasy kit.
2008-10-20 | E-GEOD-10546 | biostudies-arrayexpress
Project description:During sensitive postnatal periods, brain neural circuits undergo significant refinement coincident with widespread neuronal alternative splicing events in which hundreds of genes alter their splice site selection to generate isoforms essential for synaptic plasticity. Here, we reveal that neuronal activity-dependent serine119 phosphorylation of paxillin (p-paxillin S119) acts as a molecular switch in the nucleus to modulate alternative splicing during this period. We report that following NMDA receptor activation, nuclear p-paxillin S119 is recruited to nuclear speckles, where it interacts with U2AFs and splicing factors. Neuronal paxillin expression is required for timely alternative splicing of synaptic factors, including Snap25. Consequently, young mice lacking paxillin S119 phosphorylation exhibit significantly reduced levels of Snap25-5b isoforms, impaired presynaptic function at hippocampal Schaffer collateral-CA1 synapses, and deficits in short-term learning and memory. These findings support the idea that nuclear p-paxillin S119 is a critical mediator of alternative splicing programs in postnatal neurons during a sensitive period essential for neural plasticity.
2025-08-07 | GSE288599 | GEO
Project description:Ayurvedic drug formulations Bacopa monnieri and Centella asiatica are known to have neuroprotective effects. These have been traditionally used in the treatment of Alzhemeir’s disease, and other neurological deficits. Using pan neuronal Aβ42 model of Drosophila melanogaster, a mass spectrometry based quantitative proteomic analysis platform was used to generate the data on proteins altered in response to the Aβ42 toxicity and restoration of altered proteins by consumption of aqueous extracts of two Ayurvedic drug formulations Bacopa monnieri and Centella asiatica aqueous extract. Quantitative proteomic analysis resulted in 0.67 million mass spectra corresponding to 2,59,168 peptide-spectrum matches (PSM) mapping to 24,305 non- redundant peptides corresponding to 11,480 Drosophila melanogaster proteins. Proteins were filtered for >3 PSMs, resulting in 9,540 proteins. Flies expressing Aβ42 significantly altered 517 proteins which were involved in maintaining essential neuronal functions. Supplementing flies with Bacopa monnieri or Centella asiatica extract commonly rescued 224 proteins from Aβ42 toxicity, moreover, extract supplemented group significantly altered proteins which were additionally supporting neuronal maintenance in flies with Aβ42 stress.
2021-11-25 | PXD027101 | Pride
Project description:Neural functions and circuit establishment are characterized by intricate crosstalk among multiple cell types during critical periods. Impeding or delaying the crosstalk results in abnormal neural functions and neurodevelopmental disorders. However, the lack of robust mouse models to study the crosstalk between astrocytes and neurons thus renders unclear the implications of impeding such interactions. Here we found that Egfr knockout led to the absence of astrocytes during the critical period of neuronal maturation, with recovery observed in adult mice, providing an exceptional opportunity to investigate the consequences of delaying crosstalk between astrocytes and neurons. We show that, in the absence of Egfr, glial progenitor cells are unable to migrate outwardly, exhibiting a rounded and smooth morphology. This phenomenon arises as a direct consequence of the impaired Egfr-pERK-Epb41l2 signaling axis, leading to delayed communication between astrocytes and neurons. This delay results in reduced neuronal dendritic complexity and decreased neuronal excitability (due to damage to the Sema6a-Plxna2/4 receptor pair between astrocytes and neurons during the critical period), ultimately leading to the manifestation of depressive-like behaviors in adult mice.
2024-11-19 | PXD058068 |
Project description:Transcriptional regulation by Store-operated Calcium Entry (SOCE) is well studied in non-excitable cells. However, the role of SOCE has been poorly documented in neuronal cells with more complicated calcium dynamics. Previous reports demonstrated a requirement of neuronal SOCE for Drosophila flight. We identified the early pupal stage to be critical and used RNA-sequencing to identify SOCE mediated gene expression changes in the developing Drosophila pupal nervous system. We down-regulated dStim, the endoplasmic reticular calcium sensor and a principal component of SOCE in the nervous system for a 24h period during pupal development, and compared wild type and knockdown transcriptional profiles, immediately after knockdown as well as after a 36h recovery period. We found that dStim knockdown altered the expression of a number of genes. We also characterized one of the down-regulated genes, Ral for its role in flight. Thus, we identify neuronal SOCE as a mechanism that regulates expression of a number of genes during the development of the pupal nervous system. These genes can be further studied in the context of pupal nervous system development.
2017-03-21 | GSE89168 | GEO
Project description:In fasted mammals, glucose homeostasis is maintained through activation of the cAMP responsive CREB coactivator TORC2, which stimulates the gluconeogenic program in concert with the forkhead transcription factor FOXO1. Here we show that starvation also triggers TORC activation in Drosophila, where it maintains energy balance by promoting the expression of CREB target genes in the brain. TORC mutant flies have reduced glycogen and lipid stores, and they are sensitive to starvation as well as oxidative stress. Neuronal TORC expression rescued starvation and oxidative stress sensitivity as well as CREB target gene expression in TORC mutants. During refeeding, increases in insulin signaling inhibited TORC activity in wild type flies by stimulating the Salt Inducible Kinase 2 (SIK2)-mediated phosphorylation and subsequent degradation of TORC. Depletion of neuronal SIK2 increased TORC activity and enhanced resistance to starvation and oxidative stress in adult flies. As disruption of insulin signaling, either by ablation of insulin-producing cells (IPCs) or by mutation of the insulin receptor adaptor gene chico, also increased TORC activity, our results illustrate the importance of an insulin-regulated pathway in brain that promotes energy balance in Drosophila. Keywords: Fasting-induced gene expression
2008-07-04 | GSE10546 | GEO
Project description:Complete metamorphosis of holometabolous insects is a complex biological process characterized by profound morphological, physiological, and transcriptional changes. To reveal the temporal dynamics of gene expression during this critical developmental transition, a detailed analysis of the developmental transcriptomes of two Drosophila species, Drosophila melanogaster and Drosophila virilis, was conducted. We confirm partial recapitulation of the embryonic transcriptional program in pupae, but instead of the traditional hourglass model, which posits maximal conservation at mid-embryonic stages, at different stages of pupae we observe a more complicated pattern of alternating low and high diversity, resembling an inverted hourglass, or "spindle". This observation challenges the notion of a singular conserved phylotypic period during holometabola ontogeny and underscores the complexity of developmental processes during complete metamorphosis. Notably, recently formed genes (specific to insects) exhibit pronounced expression peaks during mid-pupal development, underscoring their potential role in developmental transitions.
2024-06-17 | GSE269951 | GEO