The miRNA pathway controls rapid changes in activity-dependent synaptic structure at the Drosophila melanogaster neuromuscular junction (miRNA array)
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ABSTRACT:
ORGANISM(S): Drosophila melanogaster
PROVIDER: GSE43943 | GEO | 2013/02/01
SECONDARY ACCESSION(S): PRJNA188193
REPOSITORIES: GEO
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Project description:It is widely accepted that long-term changes in synapse structure and function are mediated by rapid activity-dependent gene transcription and new protein synthesis. A growing amount of evidence suggests that the microRNA (miRNA) pathway plays an important role in coordinating these processes. Despite recent advances in this field, there remains a critical need to identify specific activity-regulated miRNAs as well as their key messenger RNA (mRNA) targets. To address these questions, we used the larval Drosophila melanogaster neuromuscular junction (NMJ) as a model synapse in which to identify novel miRNA-mediated mechanisms that control activity-dependent synaptic growth. First, we developed a screen to identify miRNAs differentially regulated in the larval CNS following spaced synaptic stimulation. Surprisingly, we identified five miRNAs (miRs-1, -8, -289, -314, and -958) that were significantly downregulated by activity. Neuronal misexpression of three miRNAs (miRs-8, -289, and -958) suppressed activity-dependent synaptic growth suggesting that these miRNAs control the translation of biologically relevant target mRNAs. Functional annotation cluster analysis revealed that putative targets of miRs-8 and -289 are significantly enriched in clusters involved in the control of neuronal processes including axon development, pathfinding, and growth. In support of this, miR-8 regulated the expression of a wingless 3M-bM-^@M-^YUTR (wg 3M-bM-^@M-^Y untranslated region) reporter in vitro. Wg is an important presynaptic regulatory protein required for activity-dependent axon terminal growth at the fly NMJ. In conclusion, our results are consistent with a model where key activity-regulated miRNAs are required to coordinate the expression of genes involved in activity-dependent synaptogenesis. larval CNS of UAS-ChR2 x C380-Gal4 following synaptic stimulation
2013-02-01 | E-GEOD-43943 | biostudies-arrayexpress
Project description:It is widely accepted that long-term changes in synapse structure and function are mediated by rapid activity-dependent gene transcription and new protein synthesis. A growing amount of evidence suggests that the microRNA (miRNA) pathway plays an important role in coordinating these processes. Despite recent advances in this field, there remains a critical need to identify specific activity-regulated miRNAs as well as their key messenger RNA (mRNA) targets. To address these questions, we used the larval Drosophila melanogaster neuromuscular junction (NMJ) as a model synapse in which to identify novel miRNA-mediated mechanisms that control activity-dependent synaptic growth. First, we developed a screen to identify miRNAs differentially regulated in the larval CNS following spaced synaptic stimulation. Surprisingly, we identified five miRNAs (miRs-1, -8, -289, -314, and -958) that were significantly downregulated by activity. Neuronal misexpression of three miRNAs (miRs-8, -289, and -958) suppressed activity-dependent synaptic growth suggesting that these miRNAs control the translation of biologically relevant target mRNAs. Functional annotation cluster analysis revealed that putative targets of miRs-8 and -289 are significantly enriched in clusters involved in the control of neuronal processes including axon development, pathfinding, and growth. In support of this, miR-8 regulated the expression of a wingless 3M-bM-^@M-^YUTR (wg 3M-bM-^@M-^Y untranslated region) reporter in vitro. Wg is an important presynaptic regulatory protein required for activity-dependent axon terminal growth at the fly NMJ. In conclusion, our results are consistent with a model where key activity-regulated miRNAs are required to coordinate the expression of genes involved in activity-dependent synaptogenesis. Three technical replicates (each in raw data) of three biological replicates of wild-type (CantonS) larvae in two treatment groups: (1) 5x spaced high K; (2) or 0x mock stimulation.
2013-02-01 | E-GEOD-43944 | biostudies-arrayexpress
Project description:It is widely accepted that long-term changes in synapse structure and function are mediated by rapid activity-dependent gene transcription and new protein synthesis. A growing amount of evidence suggests that the microRNA (miRNA) pathway plays an important role in coordinating these processes. Despite recent advances in this field, there remains a critical need to identify specific activity-regulated miRNAs as well as their key messenger RNA (mRNA) targets. To address these questions, we used the larval Drosophila melanogaster neuromuscular junction (NMJ) as a model synapse in which to identify novel miRNA-mediated mechanisms that control activity-dependent synaptic growth. First, we developed a screen to identify miRNAs differentially regulated in the larval CNS following spaced synaptic stimulation. Surprisingly, we identified five miRNAs (miRs-1, -8, -289, -314, and -958) that were significantly downregulated by activity. Neuronal misexpression of three miRNAs (miRs-8, -289, and -958) suppressed activity-dependent synaptic growth suggesting that these miRNAs control the translation of biologically relevant target mRNAs. Functional annotation cluster analysis revealed that putative targets of miRs-8 and -289 are significantly enriched in clusters involved in the control of neuronal processes including axon development, pathfinding, and growth. In support of this, miR-8 regulated the expression of a wingless 3’UTR (wg 3’ untranslated region) reporter in vitro. Wg is an important presynaptic regulatory protein required for activity-dependent axon terminal growth at the fly NMJ. In conclusion, our results are consistent with a model where key activity-regulated miRNAs are required to coordinate the expression of genes involved in activity-dependent synaptogenesis.
2013-02-01 | GSE43944 | GEO
Project description:Ongoing neuronal activity during development and plasticity acts to refine synaptic connections and contributes to the induction of plasticity and ultimately long term memory storage. Activity-dependent post-transcriptional control of mRNAs occurs through transport to axonal and dendritic compartments, local translation, and mRNA stability. We have identified a mechanism that contributes to activity-dependent regulation of mRNA stability during synaptic plasticity. In this study we demonstrate rapid, post-transtriptional control over process-enriched mRNAs by neuronal activity. Systematic analysis of the 3'-UTRs of destablized transcripts, identifies enrichment in sequence motifs corresponding to miRNA binding sites. The miRNAs that were identified, miR-326-3p/miR-330-5p, miR-485-5p, miR-666-3p, and miR-761 are predicted to regulate networks of genes important in plasticity and development. We find that these miRNAs are developmentally regulated in the hippocampus, many increasing by postnatal day 14. We further show that miR-485-5p controls NGF-induced neurite outgrowth in PC12 cells, tau expression, and axonal development in hippocampal neurons. miRNAs can function at the synapse to rapidly control and affect short- and long-term changes at the synapse. These processes likely occur during refinement of synaptic connections and contribute to the induction of plasticity and learning and memory. 12 hippocampal cell culture samples analysed, 3 coverslips pooled per sample. Treatments are as follows: Block: an inhibitor cocktail containing 50 µM D-APV, 40 µM CNQX, and 100 nM TTX for 3 hrs Activity: 50 µM bicuculline (BiC)/500 µM 4-Aminopyridine ActD: 25 µM actinomycin D
2014-03-12 | E-GEOD-55777 | biostudies-arrayexpress
Project description:Ongoing neuronal activity during development and plasticity acts to refine synaptic connections and contributes to the induction of plasticity and ultimately long term memory storage. Activity-dependent post-transcriptional control of mRNAs occurs through transport to axonal and dendritic compartments, local translation, and mRNA stability. We have identified a mechanism that contributes to activity-dependent regulation of mRNA stability during synaptic plasticity. In this study we demonstrate rapid, post-transtriptional control over process-enriched mRNAs by neuronal activity. Systematic analysis of the 3'-UTRs of destablized transcripts, identifies enrichment in sequence motifs corresponding to miRNA binding sites. The miRNAs that were identified, miR-326-3p/miR-330-5p, miR-485-5p, miR-666-3p, and miR-761 are predicted to regulate networks of genes important in plasticity and development. We find that these miRNAs are developmentally regulated in the hippocampus, many increasing by postnatal day 14. We further show that miR-485-5p controls NGF-induced neurite outgrowth in PC12 cells, tau expression, and axonal development in hippocampal neurons. miRNAs can function at the synapse to rapidly control and affect short- and long-term changes at the synapse. These processes likely occur during refinement of synaptic connections and contribute to the induction of plasticity and learning and memory. 12 hippocampal cell culture samples analysed, 3 coverslips pooled per sample. Treatments are as follows: Block: an inhibitor cocktail containing 50 µM D-APV, 40 µM CNQX, and 100 nM TTX for 3 hrs Activity: 50 µM bicuculline (BiC)/500 µM 4-Aminopyridine ActD: 25 µM actinomycin D
2014-03-12 | E-GEOD-55780 | biostudies-arrayexpress
Project description:Ongoing neuronal activity during development and plasticity acts to refine synaptic connections and contributes to the induction of plasticity and ultimately long term memory storage. Activity-dependent post-transcriptional control of mRNAs occurs through transport to axonal and dendritic compartments, local translation, and mRNA stability. We have identified a mechanism that contributes to activity-dependent regulation of mRNA stability during synaptic plasticity. In this study we demonstrate rapid, post-transtriptional control over process-enriched mRNAs by neuronal activity. Systematic analysis of the 3'-UTRs of destablized transcripts, identifies enrichment in sequence motifs corresponding to miRNA binding sites. The miRNAs that were identified, miR-326-3p/miR-330-5p, miR-485-5p, miR-666-3p, and miR-761 are predicted to regulate networks of genes important in plasticity and development. We find that these miRNAs are developmentally regulated in the hippocampus, many increasing by postnatal day 14. We further show that miR-485-5p controls NGF-induced neurite outgrowth in PC12 cells, tau expression, and axonal development in hippocampal neurons. miRNAs can function at the synapse to rapidly control and affect short- and long-term changes at the synapse. These processes likely occur during refinement of synaptic connections and contribute to the induction of plasticity and learning and memory. 12 hippocampal cell culture samples analysed, 3 coverslips pooled per sample. Treatments are as follows: Block: an inhibitor cocktail containing 50 µM D-APV, 40 µM CNQX, and 100 nM TTX for 3 hrs Activity: 50 µM bicuculline (BiC)/500 µM 4-Aminopyridine ActD: 25 µM actinomycin D
2014-03-12 | E-GEOD-55778 | biostudies-arrayexpress
Project description:Ongoing neuronal activity during development and plasticity acts to refine synaptic connections and contributes to the induction of plasticity and ultimately long term memory storage. Activity-dependent post-transcriptional control of mRNAs occurs through transport to axonal and dendritic compartments, local translation, and mRNA stability. We have identified a mechanism that contributes to activity-dependent regulation of mRNA stability during synaptic plasticity. In this study we demonstrate rapid, post-transtriptional control over process-enriched mRNAs by neuronal activity. Systematic analysis of the 3'-UTRs of destablized transcripts, identifies enrichment in sequence motifs corresponding to miRNA binding sites. The miRNAs that were identified, miR-326-3p/miR-330-5p, miR-485-5p, miR-666-3p, and miR-761 are predicted to regulate networks of genes important in plasticity and development. We find that these miRNAs are developmentally regulated in the hippocampus, many increasing by postnatal day 14. We further show that miR-485-5p controls NGF-induced neurite outgrowth in PC12 cells, tau expression, and axonal development in hippocampal neurons. miRNAs can function at the synapse to rapidly control and affect short- and long-term changes at the synapse. These processes likely occur during refinement of synaptic connections and contribute to the induction of plasticity and learning and memory. 4 samples analysed, 3 coverslips pooled per sample. Mouse DRG neuron cell bodies and axons were separated in multicompartment cell cultures allowing electrical stimulation of axons, growing under a high-resistance partition between compartments, through platinum electrodes in the lid of the culture dish (Reference: http://www.ncbi.nlm.nih.gov/pubmed/9295372)
2014-03-12 | E-GEOD-55779 | biostudies-arrayexpress
Project description:Ongoing neuronal activity during development and plasticity acts to refine synaptic connections and contributes to the induction of plasticity and ultimately long term memory storage. Activity-dependent post-transcriptional control of mRNAs occurs through transport to axonal and dendritic compartments, local translation, and mRNA stability. We have identified a mechanism that contributes to activity-dependent regulation of mRNA stability during synaptic plasticity. In this study we demonstrate rapid, post-transtriptional control over process-enriched mRNAs by neuronal activity. Systematic analysis of the 3'-UTRs of destablized transcripts, identifies enrichment in sequence motifs corresponding to miRNA binding sites. The miRNAs that were identified, miR-326-3p/miR-330-5p, miR-485-5p, miR-666-3p, and miR-761 are predicted to regulate networks of genes important in plasticity and development. We find that these miRNAs are developmentally regulated in the hippocampus, many increasing by postnatal day 14. We further show that miR-485-5p controls NGF-induced neurite outgrowth in PC12 cells, tau expression, and axonal development in hippocampal neurons. miRNAs can function at the synapse to rapidly control and affect short- and long-term changes at the synapse. These processes likely occur during refinement of synaptic connections and contribute to the induction of plasticity and learning and memory.
2014-03-12 | GSE55777 | GEO
Project description:Ongoing neuronal activity during development and plasticity acts to refine synaptic connections and contributes to the induction of plasticity and ultimately long term memory storage. Activity-dependent post-transcriptional control of mRNAs occurs through transport to axonal and dendritic compartments, local translation, and mRNA stability. We have identified a mechanism that contributes to activity-dependent regulation of mRNA stability during synaptic plasticity. In this study we demonstrate rapid, post-transtriptional control over process-enriched mRNAs by neuronal activity. Systematic analysis of the 3'-UTRs of destablized transcripts, identifies enrichment in sequence motifs corresponding to miRNA binding sites. The miRNAs that were identified, miR-326-3p/miR-330-5p, miR-485-5p, miR-666-3p, and miR-761 are predicted to regulate networks of genes important in plasticity and development. We find that these miRNAs are developmentally regulated in the hippocampus, many increasing by postnatal day 14. We further show that miR-485-5p controls NGF-induced neurite outgrowth in PC12 cells, tau expression, and axonal development in hippocampal neurons. miRNAs can function at the synapse to rapidly control and affect short- and long-term changes at the synapse. These processes likely occur during refinement of synaptic connections and contribute to the induction of plasticity and learning and memory.
2014-03-12 | GSE55779 | GEO
Project description:Ongoing neuronal activity during development and plasticity acts to refine synaptic connections and contributes to the induction of plasticity and ultimately long term memory storage. Activity-dependent post-transcriptional control of mRNAs occurs through transport to axonal and dendritic compartments, local translation, and mRNA stability. We have identified a mechanism that contributes to activity-dependent regulation of mRNA stability during synaptic plasticity. In this study we demonstrate rapid, post-transtriptional control over process-enriched mRNAs by neuronal activity. Systematic analysis of the 3'-UTRs of destablized transcripts, identifies enrichment in sequence motifs corresponding to miRNA binding sites. The miRNAs that were identified, miR-326-3p/miR-330-5p, miR-485-5p, miR-666-3p, and miR-761 are predicted to regulate networks of genes important in plasticity and development. We find that these miRNAs are developmentally regulated in the hippocampus, many increasing by postnatal day 14. We further show that miR-485-5p controls NGF-induced neurite outgrowth in PC12 cells, tau expression, and axonal development in hippocampal neurons. miRNAs can function at the synapse to rapidly control and affect short- and long-term changes at the synapse. These processes likely occur during refinement of synaptic connections and contribute to the induction of plasticity and learning and memory.
2014-03-12 | GSE55778 | GEO