| 1. |
- Baccino-Calace, Martin, et al.
(författare)
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Compartment and cell-type specific hypoxia responsesin the developing Drosophila brain
- 2020
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Ingår i: Biology Open. - : The Company of Biologists. - 2046-6390. ; 9:8
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Tidskriftsartikel (refereegranskat)abstract
- Environmental factors such as the availability of oxygen are instructive cues that regulate stem cell maintenance and differentiation. We used a genetically encoded biosensor to monitor the hypoxic state of neural cells in the larval brain of Drosophila. The biosensor reveals brain compartment and cell-type specific levels of hypoxia. The values correlate with differential tracheolation that is observed throughout development between the central brain and the optic lobe. Neural stem cells in both compartments show the strongest hypoxia response while intermediate progenitors, neurons and glial cells reveal weaker responses. We demonstrate that the distance between a cell and the next closest tracheole is a good predictor of the hypoxic state of that cell. Our study indicates that oxygen availability appears to be the major factor controlling the hypoxia response in the developing Drosophila brain and that cell intrinsic and cell-type specific factors contribute to modulate the response in an unexpected manner.
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| 2. |
- Beramendi, Ana, 1971-
(författare)
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Morphologican and functional studies on the Drosophila neuromuscular system during postembryonic stages
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The nervous system of the fruit fly Drosophila melanogaster has emerged as an excellent model for fundamental neuroscience as well as for biomedical research of human neurological diseases. In this thesis, two aspects of the neuromuscular system have been investigated: the role of the IkB-protein Cactus in the larval neuromuscular junction and the morphology of motor terminals throughout adult life.We found that cactus mutant larvae have poor locomotion, morphological abnormalities at the presynaptic site of motor terminals and impaired mechanical and electrophysiological properties, demonstrating that Cactus is clearly involved in the normal functioning of Drosophila neuromuscular system. In the adult, we show that cactus, dorsal and dif are expressed in the brain but are not redistributed between cytoplasm and nucleus in a circadian manner as expected from a previous finding in larval brain. Both Cactus and Dif immunoreactivity was strong in mushroom bodies and antennal lobes, suggesting a putative role in olfactory memory. In the rat, proteins of the same family are involved in the regulation of sleep but we found no indication of such regulation in flies subjected to 6 hrs of sleep deprivation.We found that neuromuscular junctions continue to change throughout adult life. Two types of long-term changes in the morphology of neuromuscular junctions are demonstrated here: a daily change in the size of synaptic boutons and long-term changes in bouton size developing over several weeks. By careful morphological studies of flight neuromuscular terminals in clock-gene mutants and wild type flies of different ages we demonstrate that the daily changes depend on the biological clock and disappear in the old fly. Moreover, we show that light is necessary for the motor neurons studied to reach maximum size of synaptic boutons. Lastly, we found that the two clock genes period and timeless are also necessary to control axonal branching.Transmission electron microscopy revealed several ultrastructural features distinct of the aging fly and indicative of reduced plasticity. We used a temperature-sensitive allele of shibire that rapidly and reversibly blocks vesicle recycling to investigate whether the morphological phenotype found in neuromuscular junctions of aging flies could be explained by impairment of endocytotic mechanisms. Our results show a clear reduction of the time required for complete paralysis and an increased recovery time in old flies, indicating that aging correlates with impaired endocytosis and membrane dynamics.
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| 3. |
- Beramendi, Ana, et al.
(författare)
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Neuromuscular junction in abdominal muscles of Drosophila melanogaster during adulthood and aging
- 2007
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Ingår i: Journal of Comparative Neurology. - : Wiley. - 0021-9967 .- 1096-9861. ; 501:4, s. 498-508
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Tidskriftsartikel (refereegranskat)abstract
- The neuromuscular junction (NMJ) of Drosophila melanogaster has been established as a productive model for the study of synaptogenesis, synaptic plasticity, vesicle recycling, and other synaptic functions in embryos and larvae. It also has potential for the study of long-term plasticity during adult life and degenerative processes associated with aging. Here we provide a detailed description of the morphology and ultrastructure of the NMJ on abdominal dorsal longitudinal muscles throughout adult life from eclosion to senescence. In contrast to the case in the larva, the predominant type of terminals in these muscles in the adult fly consists of only two or three branches with tightly packed synaptic boutons. We observed qualitative and quantitative changes as mean bouton size increased gradually during adulthood, and the largest boutons were present in the old fly. The length of nerve branches first increased and thereafter decreased gradually during most of adult life. Branch diameter also decreased progressively, but branch number did not change. The subsynaptic reticulum became progressively thinner, and “naked” boutons were found in old flies. Ultrastructural traits gave indications of an age-associated increment in autophagy, larger synaptic vesicles, and impaired endocytosis. We propose that NMJ aging in the fly correlates with impaired endocytosis and membrane dynamics. This view finds a functional correlate in flies carrying a temperature-sensitive mutation in shibire that reversible blocks endocytosis; age significantly reduces the time required for complete paralysis and increases the time of recovery, thus confirming the age-dependent alteration in vesicle dynamics.
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| 4. |
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| 5. |
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| 6. |
- Cantera, Rafael, et al.
(författare)
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Do the Genes of the Innate Immune Response Contribute to Neuroprotection in Drosophila?
- 2015
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Ingår i: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 7:1, s. 3-10
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Forskningsöversikt (refereegranskat)abstract
- A profound debate exists on the relationship between neurodegeneration and the innate immune response in humans. Although it is clear that such a relation exists, the causes and consequences of this complex association remain to be determined in detail. Drosophila is being used to investigate the mechanisms involved in neurodegeneration, and all genomic studies on this issue have generated gene catalogues enriched in genes of the innate immune response. We review the data reported in these publications and propose that the abundance of immune genes in studies of neurodegeneration reflects at least two phenomena: (i) some proteins have functions in both immune and nervous systems, and (ii) immune genes might also be of neuroprotective value in Drosophila. This review opens this debate in Drosophila, which could thus be used as an instrumental model to elucidate this question.
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| 7. |
- Cantera, Rafael, et al.
(författare)
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Global Gene Expression Shift during the Transition from Early Neural Development to Late Neuronal Differentiation in Drosophila melanogaster
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- Regulation of transcription is one of the mechanisms involved in animal development, directing changes in patterning and cell fate specification. Large temporal data series, based on microarrays across the life cycle of the fly Drosophila melanogaster, revealed the existence of groups of genes which expression increases or decreases temporally correlated during the life cycle. These groups of genes are enriched in different biological functions. Here, instead of searching for temporal coincidence in gene expression using the entire genome expression data, we searched for temporal coincidence in gene expression only within predefined catalogues of functionally related genes and investigated whether a catalogue's expression profile can be used to generate larger catalogues, enriched in genes necessary for the same function. We analyzed the expression profiles from genes already associated with early neurodevelopment and late neurodifferentiation, at embryonic stages 16 and 17 of Drosophila life cycle. We hypothesized that during this interval we would find global downregulation of genes important for early neuronal development together with global upregulation of genes necessary for the final differentiation of neurons. Our results were consistent with this hypothesis. We then investigated if the expression profile of gene catalogues representing particular processes of neural development matched the temporal sequence along which these processes occur. The profiles of genes involved in patterning, neurogenesis, axogenesis or synaptic transmission matched the prediction, with largest transcript values at the time when the corresponding biological process takes place in the embryo. Furthermore, we obtained catalogues enriched in genes involved in temporally matching functions by performing a genome-wide systematic search for genes with their highest expression levels at the corresponding embryonic intervals. These findings imply the use of gene expression data in combination with known biological information to predict the involvement of functionally uncharacterized genes in particular biological events.
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| 8. |
- Fernandez-Acosta, Magdalena, et al.
(författare)
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orsai, the Drosophila homolog of human ETFRF1, links lipid catabolism to growth control
- 2022
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Ingår i: BMC Biology. - : Springer Science and Business Media LLC. - 1741-7007. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lipid homeostasis is an evolutionarily conserved process that is crucial for energy production, storage and consumption. Drosophila larvae feed continuously to achieve the roughly 200-fold increase in size and accumulate sufficient reserves to provide all energy and nutrients necessary for the development of the adult fly. The mechanisms controlling this metabolic program are poorly understood.Results: Herein we identified a highly conserved gene, orsai (osi), as a key player in lipid metabolism in Drosophila. Lack of osi function in the larval fat body, the regulatory hub of lipid homeostasis, reduces lipid reserves and energy output, evidenced by decreased ATP production and increased ROS levels. Metabolic defects due to reduced Orsai (Osi) in time trigger defective food-seeking behavior and lethality. Further, we demonstrate that downregulation of Lipase 3, a fat body-specific lipase involved in lipid catabolism in response to starvation, rescues the reduced lipid droplet size associated with defective orsai. Finally, we show that osi-related phenotypes are rescued through the expression of its human ortholog ETFRF1/LYRm5, known to modulate the entry of β-oxidation products into the electron transport chain; moreover, knocking down electron transport flavoproteins EtfQ0 and walrus/ETFA rescues osi-related phenotypes, further supporting this mode of action.Conclusions: These findings suggest that Osi may act in concert with the ETF complex to coordinate lipid homeostasis in the fat body in response to stage-specific demands, supporting cellular functions that in turn result in an adaptive behavioral response.
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| 9. |
- Frank, Marcos G., et al.
(författare)
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Sleep, clocks, and synaptic plasticity
- 2014
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Ingår i: TINS - Trends in Neurosciences. - : Elsevier BV. - 0166-2236 .- 1878-108X. ; 37:9, s. 491-501
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Forskningsöversikt (refereegranskat)abstract
- Sleep is widely believed to play an essential role in synaptic plasticity. However, the precise mechanisms governing this presumptive function are largely unknown. There is also evidence for independent circadian oscillations in synaptic strength and morphology. Therefore, synaptic changes observed after sleep reflect interactions between state-dependent (e.g., wake versus sleep) and state-independent (circadian) processes. In this review we consider how sleep and biological clocks influence synaptic plasticity. We discuss these findings in the context of current plasticity-based theories of sleep function and propose a new model that integrates circadian and brain-state influences on synaptic plasticity.
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| 10. |
- Gruber, Lydia, et al.
(författare)
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Synaptic Spinules in the Olfactory Circuit of Drosophila melanogaster
- 2018
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Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Here we report on ultrastructural features of brain synapses in the fly Drosophila melanogaster and outline a perspective for the study of their functional significance. Images taken with the aid of focused ion beam-scanning electron microscopy (EM) at 20 nm intervals across olfactory glomerulus DA2 revealed that some synaptic boutons are penetrated by protrusions emanating from other neurons. Similar structures in the brain of mammals are known as synaptic spinules. A survey with transmission EM (TEM) disclosed that these structures are frequent throughout the antennal lobe. Detailed neuronal tracings revealed that spinules are formed by all three major types of neurons innervating glomerulus DA2 but the olfactory sensory neurons (OSNs) receive significantly more spinules than other olfactory neurons. Double-membrane vesicles (DMVs) that appear to represent material that has pinched-off from spinules are also most abundant in presynaptic boutons of OSNs. Inside the host neuron, a close association was observed between spinules, the endoplasmic reticulum (ER) and mitochondria. We propose that by releasing material into the host neuron, through a process triggered by synaptic activity and analogous to axonal pruning, synaptic spinules could function as a mechanism for synapse tagging, synaptic remodeling and neural plasticity. Future directions of experimental work to investigate this theory are proposed.
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