Loss of dihydroceramide desaturase drives neurodegeneration by disrupting endoplasmic reticulum and lipid droplet homeostasis in glial cells DOI Open Access
Yuqing Zhu, Kevin Cho, Haluk Lacin

и другие.

Опубликована: Июль 31, 2024

Dihydroceramide desaturases convert dihydroceramides to ceramides, the precursors of all complex sphingolipids. Reduction DEGS1 dihydroceramide desaturase function causes pediatric neurodegenerative disorder hypomyelinating leukodystrophy-18 (HLD-18). We discovered that infertile crescent (ifc) , Drosophila homolog, is expressed primarily in glial cells promote CNS development by guarding against neurodegeneration. Loss ifc massive accumulation and severe morphological defects cortex glia, including endoplasmic reticulum (ER) expansion, failure neuronal ensheathment, lipid droplet depletion. RNAi knockdown upstream ceramide synthase schlank glia mutants rescues ER suggesting drives this phenotype. but not neurons cell death, promotes survival. Our work identifies as primary site disease progression HLD-18 may inform on juvenile forms ALS, which also feature elevated levels.

Язык: Английский

Ca2+ excitability of glia to neuromodulator octopamine in Drosophila living brain is greater than that of neurons DOI Creative Commons

Urška Černe,

Anemari Horvat,

Ena Sanjković

и другие.

Acta Physiologica, Год журнала: 2025, Номер 241(2)

Опубликована: Янв. 13, 2025

Octopamine in the Drosophila brain has a neuromodulatory role similar to that of noradrenaline mammals. After release from Tdc2 neurons, octopamine/tyramine may trigger intracellular Ca We expressed Octopamine-stimulated In optic lobes, astrocytes, not appear be sole responders low concentration octopamine signals, and therefore likely drive synaptic plasticity visual processing. Given interconnectivity lobes with other regions, octopaminergic signals acting through lobe astrocytes also influence higher-order functions including learning memory.

Язык: Английский

Процитировано

1
Glial overexpression of Tspo extends lifespan and protects against frataxin deficiency in Drosophila DOI Creative Commons

Estelle Jullian,

Maria Russi,

Ema Turki

и другие.

Biochimie, Год журнала: 2024, Номер 224, С. 71 - 79

Опубликована: Май 14, 2024

The translocator protein TSPO is an evolutionary conserved mitochondrial overexpressed in various contexts of neurodegeneration. Friedreich Ataxia (FA) a neurodegenerative disease due to GAA expansions the FXN gene leading decreased expression frataxin, involved biosynthesis iron-sulfur clusters. We previously reported that Tspo was Drosophila model this generated by CRISPR/Cas9 insertion approximately 200 intron fh, fly frataxin gene. Here, we describe new FA with 42 repeats, called fh-GAAs. smaller expansion size allowed obtain adults exhibiting hallmarks disease, including short lifespan, locomotory defects and hypersensitivity oxidative stress. reduced lifespan fully rescued ubiquitous human FXN, confirming both frataxins share functions. observed heads intestines these fh-GAAs flies. Then, further specifically glial cells improved survival. Finally, investigated effects overexpression healthy Increased longevity conferred glial-specific overexpression, opposite neurons. Overall, study highlights protective context.

Язык: Английский

Процитировано

4
Glial metabolism versatility regulates mushroom body–driven behavioral output inDrosophila DOI Open Access

Ruchira Basu,

Thomas Préat, Pierre-Yves Plaçais

и другие.

Learning & Memory, Год журнала: 2024, Номер 31(5), С. a053823 - a053823

Опубликована: Май 1, 2024

Providing metabolic support to neurons is now recognized as a major function of glial cells that conserved from invertebrates vertebrates. However, research in this field has focused for more than two decades on the relevance lactate and glycolysis neuronal energy metabolism, while overlooking many other facets metabolism their impact physiology, circuit activity, behavior. Here, we review recent work unveiled new features especially Drosophila , modulation behavioral traits involving mushroom bodies (MBs). These findings reveal spatially biochemically distinct modes glucose-derived fueling are implemented within MB memory type–specific manner. In addition, cortex glia endowed with several antioxidant functions, whereas astrocytes can serve pro-oxidant agents beneficial redox signaling underlying long-term memory. Finally, fatty acid oxidation seems play dual fail-safe role: first, mode production upon glucose shortage, and, second, factor clearance excessive oxidative load during sleep. Altogether, these integrated studies performed indicate deterministic role

Язык: Английский

Процитировано

3
Cell-specific genetic expression profile of antennal glia in Drosophila reveals candidate genes in neuron-glia interactions DOI Creative Commons
Ana Castañeda-Sampedro, Esther Alcorta, Carolina Gomez‐Diaz

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 14, 2025

Язык: Английский

Процитировано

0
Linking expression and function of Drosophila type-I TGF-β receptor baboon isoforms: Multiple roles of BaboA isoform in shaping of the adult central nervous system DOI Creative Commons
Gyunghee Lee, Aidan J. Peterson, Myung-Jun Kim

и другие.

PLoS ONE, Год журнала: 2025, Номер 20(5), С. e0318406 - e0318406

Опубликована: Май 30, 2025

Evolutionarily conserved transforming growth factor β (TGF-β) signaling is used in both vertebrates and invertebrates to regulate a variety of developmental cellular processes. The baboon ( babo ) gene encoding Drosophila type-I TGF-β receptor produces three isoforms via alternative splicing: BaboA, BaboB, BaboC. In this study, we generated fly lines, each carrying an isoform-specific GFP tag, another line with conjugated at the C-terminus common all isoforms. Using these assessed (1) whether tagged proteins function properly rescue assays (2) how isoform expression regulated various tissues including central nervous system (CNS). A Gal4 knock-in locus was also characterized for reporter expression, mutant phenotypes, knockdown phenotypes. We found that C-terminal tag does not interrupt subcellular targeting functions isoforms, but internal tags do so cell- fashion. Nevertheless, our results demonstrated faithfully reflect endogenous individual Certain cell types express single or multiple different levels, suggesting splicing could determine their levels depending on (or tissue) type. larval CNS displays distinct patterns two BaboA BaboC mostly expressed neural cells originating during embryogenesis, while broadly produced from embryonic postembryonic stages. Assays mutants cell-specific revealed broad roles played by neurogenesis differentiation precursor neurons, remodeling processes persisting metamorphic reorganization, which are essential establishing adult CNS. Taken together, study demonstrates GFP-tagged lines permit visualization further provides clues about stage-specific isoform.

Язык: Английский

Процитировано

0
Early Draper-mediated glial refinement of neuropil architecture and synapse number in the Drosophila antennal lobe DOI Creative Commons

Darren A Jindal,

Hans C. Leier, Gabriela Salazar

и другие.

Frontiers in Cellular Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Июнь 2, 2023

Glial phagocytic activity refines connectivity, though molecular mechanisms regulating this exquisitely sensitive process are incompletely defined. We developed the Drosophila antennal lobe as a model for identifying underlying glial refinement of neural circuits in absence injury. Antennal organization is stereotyped and characterized by individual glomeruli comprised unique olfactory receptor neuronal (ORN) populations. The interacts extensively with two subtypes: ensheathing glia wrap glomeruli, while astrocytes ramify considerably within them. Phagocytic roles uninjured largely unknown. Thus, we tested whether Draper regulates ORN terminal arbor size, shape, or presynaptic content representative glomeruli: VC1 VM7. find that limits size restrains their content. Moreover, apparent young adults, period rapid synapse growth, indicating addition elimination occur simultaneously. has been shown to be expressed glia; unexpectedly, it at high levels late pupal astrocytes. Surprisingly, plays differential In VC1, more significant role shaping glomerular content; VM7, astrocytic larger role. Together, these data indicate employ refine circuitry before arbors reach mature form argue local heterogeneity neuron-glia interactions.

Язык: Английский

Процитировано

8
Drosophila melanogaster models of MPS IIIC (Hgsnat‐deficiency) highlight the role of glia in disease presentation DOI Creative Commons

Laura J. Hewson,

Amanda Choo,

Dani L. Webber

и другие.

Journal of Inherited Metabolic Disease, Год журнала: 2024, Номер 47(2), С. 340 - 354

Опубликована: Янв. 18, 2024

Abstract Sanfilippo syndrome (Mucopolysaccharidosis type III or MPS III) is a recessively inherited neurodegenerative lysosomal storage disorder. Mutations in genes encoding enzymes the heparan sulphate degradation pathway lead to accumulation of partially degraded sulphate, resulting ultimately development neurological deficits. gene membrane protein heparan‐α‐glucosaminide N ‐acetyltransferase ( HGSNAT ; EC2.3.1.78) cause IIIC (OMIM#252930), typified by impaired cognition, sleep–wake cycle changes, hyperactivity and early death, often before adulthood. The precise disease mechanism that causes symptom emergence remains unknown, posing significant challenge effective therapeutics. As conserved Drosophila melanogaster , we now describe creation characterisation first models IIIC. Flies with either an endogenous insertion mutation RNAi‐mediated knockdown hgsnat were confirmed have reduced level transcripts age‐dependent leading engorgement endo/lysosomal compartment. This resulted abnormalities at pre‐synapse, defective climbing overall activity. Altered circadian rhythms (shift peak morning activity) seen neuronal lines. Further, when was knocked down specific glial subsets (wrapping, cortical, astrocytes subperineural glia), activity noted, implying function these subtypes contributes significantly this behaviour targeting treatments cell groups may be necessary ameliorate prevent onset. These novel provide critical research tools for delineating key cellular pathways causal onset neurodegeneration presently untreatable

Язык: Английский

Процитировано

2
A single-cell 3D spatiotemporal multi-omics atlas fromDrosophilaembryogenesis to metamorphosis DOI Creative Commons
Mingyue Wang, Qinan Hu, Zhencheng Tu

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 6, 2024

SUMMARY The development of a multicellular organism is highly intricate process tightly regulated by numerous genes and pathways in both spatial temporal manners. Here, we present Flysta3D, comprehensive multi-omics atlas the model Drosophila , spanning its developmental lifespan from embryo to pupa. Our datasets encompass 3D single-cell transcriptomic, chromatin accessibility information. By integrating these multi-dimensional data, constructed cell state trajectories that uncover detailed profiles tissue development. With focus on central nervous system (CNS) midgut, dissected spatiotemporal dynamics gene regulatory networks, type diversity, morphological changes perspective. This extensive provides an unprecedentedly rich resource serves as systematic platform for studying with integrated data at ultra-high resolution.

Язык: Английский

Процитировано

2
Loss of dihydroceramide desaturase drives neurodegeneration by disrupting endoplasmic reticulum and lipid droplet homeostasis in glial cells DOI Creative Commons
Yuqing Zhu, Kevin Cho, Haluk Lacin

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Янв. 2, 2024

Dihydroceramide desaturases convert dihydroceramides to ceramides, the precursors of all complex sphingolipids. Reduction DEGS1 dihydroceramide desaturase function causes pediatric neurodegenerative disorder hypomyelinating leukodystrophy-18 (HLD-18). We discovered that infertile crescent (ifc), Drosophila homolog, is expressed primarily in glial cells promote CNS development by guarding against neurodegeneration. Loss ifc massive accumulation and severe morphological defects cortex glia, including endoplasmic reticulum (ER) expansion, failure neuronal ensheathment, lipid droplet depletion. RNAi knockdown upstream ceramide synthase schlank glia mutants rescues ER suggesting drives this phenotype. but not neurons cell death, promotes survival. Our work identifies as primary site disease progression HLD-18 may inform on juvenile forms ALS, which also feature elevated levels.

Язык: Английский

Процитировано

1
Homemade: building the structure of the neurogenic niche DOI Creative Commons

Ghanim Fajish Valamparamban,

Pauline Spéder

Frontiers in Cell and Developmental Biology, Год журнала: 2023, Номер 11

Опубликована: Дек. 1, 2023

Neural stem/progenitor cells live in an intricate cellular environment, the neurogenic niche, which supports their function and enables neurogenesis. The niche is made of a diversity cell types, including neurons, glia vasculature, are able to signal structurally organised around neural cells. While focus has been on how individual types influence behaviour cells, very little actually known assembled during development from multiple origins, role resulting topology these This review proposes draw state-of-the art picture this emerging field research, with aim expose our knowledge architecture formation different animal models (mouse, zebrafish fruit fly). We will span its aspects, existence importance local, adhesive interactions potential emergence larger-scale topological properties through careful assembly diverse acellular components.

Язык: Английский

Процитировано

3