Drosophila glia: Few cell types and many conserved functions

Glia, Journal Year: 2018, Volume and Issue: 67(1), P. 5 - 26

Published: Nov. 15, 2018

Abstract Glial cells constitute without any dispute an essential element in providing efficiently operating nervous system. Work many labs over the last decades has demonstrated that neuronal function, from action potential generation to its propagation, eliciting synaptic responses subsequent postsynaptic integration, is evolutionarily highly conserved. Likewise, biology of glial appears conserved core elements and therefore, a deeper understanding expected benefit analyzing model organisms such as Drosophila melanogaster . particularly well suited for studying since fly system only limited number exists, which can be individually identified based on position set molecular markers. In combination with well‐known genetic tool box unprecedented level analysis feasible, not help identify novel molecules principles governing cell function but also will better understand functions first mammalian Here we review current knowledge glia spark interest using this analyze complex traits future.

Language: Английский

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Neuron–glia interaction in the Drosophila nervous system

Developmental Neurobiology, Journal Year: 2020, Volume and Issue: 81(5), P. 438 - 452

Published: Feb. 25, 2020

Abstract Animals are able to move and react in manifold ways external stimuli. Thus, environmental stimuli need be detected, information must processed, and, finally, an output decision transmitted the musculature get animal moving. All these processes depend on nervous system which comprises intricate neuronal network many glial cells. Glial cells have equally important contribution function as their counterpart. Manifold roles attributed glia ranging from controlling cell number axonal pathfinding regulation of synapse formation, function, plasticity. metabolically support neurons contribute blood–brain barrier. aforementioned aspects require extensive cell–cell interactions between Not surprisingly, found all phyla executed by evolutionarily conserved molecules. Here, we review recent advance understanding neuron–glia interaction Drosophila melanogaster suggest that work simple model organisms will shed light mammalian cells, too.

Language: Английский

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Drosophila postembryonic nervous system development: a model for the endocrine control of development

Genetics, Journal Year: 2023, Volume and Issue: 223(3)

Published: Jan. 16, 2023

Abstract During postembryonic life, hormones, including ecdysteroids, juvenile insulin-like peptides, and activin/TGFβ ligands act to transform the larval nervous system into an adult version, which is a fine-grained mosaic of recycled neurons adult-specific neurons. Hormones provide both instructional signals that make cells competent undergo developmental change timing cues evoke these changes across system. While touching on all above our emphasis ecdysone 20-hydroxyecdysone (20E). These are prime movers insect molting metamorphosis involved in phases development, neurogenesis, pruning, arbor outgrowth, cell death. Ecdysteroids appear as series steroid peaks coordinate molts different metamorphosis. Each peak directs stereotyped cascade transcription factor expression. The components then direct temporal programs effector gene expression, but latter vary markedly according tissue life stage. read ecdysteroid titer through various isoforms receptor, nuclear hormone receptor. For example, at pruning mediated B isoforms, have strong activation functions, whereas subsequent outgrowth A isoform ecdysteroids play permissive role allow local interactions outgrowth. major circulating can also development. development promotes early patterning differentiation while its metabolite, 20E, later evokes terminal differentiation.

Language: Английский

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CATaDa reveals global remodelling of chromatin accessibility during stem cell differentiation in vivo

eLife, Journal Year: 2018, Volume and Issue: 7

Published: Feb. 23, 2018

Article Figures and data Abstract eLife digest Introduction Results Discussion Materials methods Data availability References Decision letter Author response author information Metrics During development eukaryotic gene expression is coordinated by dynamic changes in chromatin structure. Measurements of accessible are used extensively to identify genomic regulatory elements. Whilst landscapes pluripotent stem cells well characterised, accessibility the somatic lineages not defined. Here we show that cell-specific can be produced via ectopic E. coli Dam methylase vivo, without requirement for cell-sorting (CATaDa). We have profiled individual cell-types Drosophila neural midgut lineages. Functional cell-type-specific enhancers were identified, as novel motifs enriched at different stages development. Finally, global between stem-cells their differentiated progeny. Our results demonstrate nature tissues during cell differentiation provide a approach understanding mechanisms underlying https://doi.org/10.7554/eLife.32341.001 For an embryo successfully develop into adult animal, specific genes must act types cells. Though all same encoded within DNA, looking way DNA packaged indicate which parts important particular type. If regions “open” one infer those actively involved regulation, whereas “closed” considered less important. It currently difficult determine open type complex organ, such brain. Existing require physically isolated from tissue, technically challenging. To overcome this issue, Aughey et al. now developed method does isolation The new technique involves using genetic engineering introduce enzyme called living fruit flies. This adds chemical label on then detected. tested various developing brain gut, able see differences openness corresponded action each also contain trends help understand role example, mature shown overall than divide generate them. hope will use other researchers working with either flies or mammalian tissues. knowledge scientists gain identifying how contributes both healthy diseased tissues, further our human biology diseases cancer. https://doi.org/10.7554/eLife.32341.002 multicellular organism, tightly regulated spatially temporally restricted signals. Changes accompanied concomitant structure composition. Therefore states vary widely across developmental types. genome, including promoters enhancers, identified relative lack nucleosomes. These ‘open chromatin’ assayed extrinsic factors. Consequently, profiling techniques commonly investigate (reviewed [Tsompana Buck, 2014]). Chromatin highly embryonic (ES) cells, but compacted following (Meshorer Misteli, 2006). has been suggested represents permissive state multiple programmes regulation may rapidly applied upon (Gaspar-Maia al., 2011). vivo understood. Imaging studies gross structure, example distribution heterochromatin observed post-mitotic (Francastel 2000; Le Gros 2016). Molecular investigating tended utilise heterogeneous due fact epigenome frequently requires physical nuclei, laborious prone error (McClure Southall, 2015). Therefore, there regarding models. recently ATAC-seq become popular address many limitations inherent earlier DNAse-seq (i.e. fewer increased assay speed), these still separation before (Buenrostro 2013). untethered adenine methyltransferase (Dam) methylation whilst nucleosome bound protected (Wines 1996; Bulanenkova 2007; Boivin Dura, 1998; Singh Klar, 1992). However, efficacy scale clear. Furthermore, manner, levels low enough avoid toxicity oversaturated signal, possible until now. Transgenic fusions DNA-binding proteins well-established assess transcription factor occupancy (DNA identification - DamID) (van Steensel Henikoff, 2000). Recently, it was demonstrated DamID could adapted profile DNA-protein interactions manner utilising ribosome re-initiation attenuate transgene (Marshall 2016; Southall referred Targeted (TaDa). Here, take advantage TaDa express produce profiles separation. Accessibility (CATaDa) yields comparable FAIRE methods, indicating reliable reproducible states. By assaying throughout central nervous system (CNS) enabled us elements dynamically change differentiation, functional enhancers. compared progeny, Dam-methylation signals more distributed greater level accessibility. CATaDa produces ATAC FAIRE-seq eye discs reasoned low-level transgenic Dam, tissue-specific GAL4 drivers Drosophila, would specifically methylate exclusively cell-type interest. Detection methylated sequences yield defined populations (Figure 1). if accurate reflection accessibility, acquired alternative techniques. A recent study generated imaginal (Davie Using CATaDa, expressed disc third instar larvae so compare previously collected data. Figure 1 Download asset Open Schematic illustrating technique. (A–B) interest (C) GATC areas condensed prevent access thereby precluding methylation. (D) Methylated detected mixed population https://doi.org/10.7554/eLife.32341.003 replicates (r2 = 0.947) 2—figure supplement showed good agreement FAIRE-seq. Visual inspection represented reliably inaccessible 2A,B). observe exhibited features consistent transcriptional start sites (TSS) 2C). 2 3 supplements Validation (A) chromosome three determined ATAC-seq, FAIRE-seq, CATaDa. Note reduced amount proximal centromere datasets. y-axes reads per million (rpm). (B) Example locus showing obtained FAIRE, ATAC, Peaks broadly Aggregation plot signal TSS kb up downstream. Aggregated shows expected enrichment Dam. peaks, loci. (E) Identification peaks 48.6% 55.9% respectively. overlap promoter (2 TSS), outside regions. https://doi.org/10.7554/eLife.32341.004 frequency increases dramatically towards centre 2D).The 49.4%, respectively (In comparison, – 2E). Monte Carlo simulation significant (p<1 × 10−5) peak heights shared correlation 10-16, r2 0.138) 2A). found increasing stringency calling notably decreased number coincided had relatively little impact unique discovery 2B). Given data, suggest majority false positives, genuinely ATAC-seq. Further examination indicates they significantly smaller present motifs, suggests cases negatives resolution achievable 3A–B). investigated detection features. (when ATAC), better non-promoter adjacent again explained depletion upstream 3C). high experimentally validated eye-antennal similarly 3A,B). 57.9% FlyLight corresponding (333 575 enhancers). 48% 68.7% respectively, loci Flylight coincide Corresponding pattern (i) (ii) (eye images database [http://flweb.janelia.org/cgi-bin/flew.cgi]). average (blue) (green) expression. Both Venn diagram profiling, most (305 total https://doi.org/10.7554/eLife.32341.008 In neurons derived asymmetrically dividing (NSCs). NSC divisions self-renewing daughter ganglion mother (GMC), divides once glia (Homem Knoblich, 2012). test local process cover four lineage. include NSCs (worniu- GAL4), GMCs newly born (R71C09-GAL4 [Figure 4—figure 1B, Li 2014]), larval (nSyb-GAL4), (nSyb-GAL4) 4A). 4 5 CNS. CNS lineage progression examined study. resulting Genomic region encompassing Wnt2 bruchpilot shown. Multiple Y-axes Clustering differentially two major groupings neurons. Motif analysis (e.g. ase E-box motif loci), motifs. Most cluster All E-values < 10−5. log2 scores selected GO terms Clear seen progresses. (NSC, GMC, L3 neuron, neuron left right). becoming progresses vice versa. https://doi.org/10.7554/eLife.32341.009 examining candidate development, relates manner. intronic (brp) locus, (L3) neurons, absent progenitor 4B). corresponds brp, transcribed synapse function (Wagh contrast, Wnt2, displays apparent intermediate Wnt signalling known control populations, therefore, (Ring 2014). Similar patterns At asense (ase) (a NSC-specific factor), intergenic considerably fully expressed. Interestingly, detectable GMCs/newly factors deadpan (dpn), CyclinE (CycE) prospero (pros) 2). GMC/newly loci, required immediately rendered 4B marked regulating given neurons). differential extent changed system. Hierarchical clustering reveals clusters versa 4C). Intriguingly, where maximal GMCs/early simple progressively closing neuronal gradually opening. There large NSCs, stage being terminally addition, demonstrates landscape although similar, distinct Regions thought belonging neurogenesis. binding enriched. CAGCNG proneural 4D) (Southall Brand, 2009; Jarman 1993). yielded sequence factor, Ci. groups, no partner 3). Analysis subdivision revealed yet examined, ase-like solely progeny 4). Gene ontology (GO) biological 5). ‘neuroblast fate determination’ ‘chromosome segregation’ ‘regulation behaviour’ ‘synaptic vesicle docking exocytosis’ 4E). Having CNS, asked whether similar contains pool cycling intestinal (ISCs) persists maintain mediate absorptive secretory functions organ (Jiang Edgar, 2011; Nászai contrast neurogenesis, single committed immature (enteroblast EB) divisions, differentiates epithelial (Ohlstein Spradling, 2007). examine midgut, ISCs EBs, enterocytes (ECs)(Figure 5A). midgut. escargot ECs. Upstream greatest ISCs, Similarly, 3’ 5’ distal (putative enhancer regions), nubbin gut Major ECs, down-regulated EBs. Principal component (mean replicates) (F) Correlation matrix (Spearman’s rank) means Individual denoted red outline. ISC (Asterisk R2 0.76), EC comparable. https://doi.org/10.7554/eLife.32341.016 As predictable variable (esg) self-renewal (Korzelius 2014), body surrounding ECs 5B). (encoding marker Pdm1), predominantly closed 5C). hierarchical groups (ECs) 5D). Smaller evident downregulated much pronounced that, lineages, specifying do occur after EB maturation. 5—figure fulfil roles respective organs production specialised exist short time fly long-lived persist animal’s lifetime, post-developmentally constantly replenish gut. comparing types, similarities growth division, tissue queried scale. >80% variance first principal components 5E). represent (CNS midgut) rather interesting Firstly, correlated closely direct 5F). recapitulate familial relationship progenitors cognate (R2 0.94/0.98 respectively). only weak (ISCs vs NSC, 0.51). maintenance multipotency, lineage-specific variation small. Enhancer prediction activity linked expression, orchestrate correct spatial temporal (Pennacchio 2015; Crawford cell-type- support this, covered 71C09-GAL4 line displayed higher clear reporter necessarily correspond active previous observations DNase hypersensitive often (Zhou 2017; Thurman least lineage, satisfied criteria designate them putative (see methods). available lines Vienna tiles (VT)(Kvon 2014) (Jenett 2012) collections contained predicted reporter, verified enhancer-GAL4 matched predictions activity. VT017417 GMR56E07 early part GFP 6A,B). readings prominent did not. detect line, VT004241, Delta positive 6C).

Language: Английский

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Quiescent Neural Stem Cells for Brain Repair and Regeneration: Lessons from Model Systems

Trends in Neurosciences, Journal Year: 2020, Volume and Issue: 43(4), P. 213 - 226

Published: March 9, 2020

Language: Английский

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Neurogenesis From Embryo to Adult – Lessons From Flies and Mice

Frontiers in Cell and Developmental Biology, Journal Year: 2020, Volume and Issue: 8

Published: June 30, 2020

The human brain is composed of billions cells, including neurons and glia, with an undetermined number subtypes. During the embryonic early postnatal stages, vast majority these cells are generated from neural progenitors stem located in all regions tube. A smaller will continue to be throughout our lives, localized neurogenic zones, mainly confined at least rodents subependymal zone lateral ventricles subgranular hippocampal dentate gyrus. neurogenesis, a combination extrinsic cues interacting temporal regional intrinsic programs thought critical for increasing neuronal diversity, but their underlying mechanisms need further elucidation. In this review, we discuss recent findings Drosophila mammals on types cell division interactions used by sustain how they influenced glia.

Language: Английский

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More Than Mortar: Glia as Architects of Nervous System Development and Disease

Frontiers in Cell and Developmental Biology, Journal Year: 2020, Volume and Issue: 8

Published: Dec. 14, 2020

Glial cells are an essential component of the nervous system vertebrates and invertebrates. In human brain, glia as numerous neurons, yet importance to nearly every aspect development has only been expounded over last several decades. Glia now known regulate neural specification, synaptogenesis, synapse function, even broad circuit function. Given their ubiquity, it is not surprising that contribution neuronal disease pathogenesis a growing area research. this review, we will summarize accumulated evidence glial participation in distinct phases organization—neural wiring, Finally, highlight how these early developmental roles contribute dysfunction neurodevelopmental neurodegenerative disorders.

Language: Английский

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Waking up quiescent neural stem cells: Molecular mechanisms and implications in neurodevelopmental disorders

PLoS Genetics, Journal Year: 2020, Volume and Issue: 16(4), P. e1008653 - e1008653

Published: April 23, 2020

Neural stem cells (NSCs) are crucial for development, regeneration, and repair of the nervous system. Most NSCs in mammalian adult brains quiescent, but response to extrinsic stimuli, they can exit from quiescence become reactivated give rise new neurons. The delicate balance between NSC activation is important neurogenesis maintenance. However, how transit remains largely elusive. Here, we discuss our current understanding molecular mechanisms underlying reactivation quiescent NSCs. We review recent advances on signaling pathways originated niche their crosstalk regulating reactivation. also highlight intrinsic paradigms that control Drosophila systems. emerging evidence modeling human neurodevelopmental disorders using

Language: Английский

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Dilp-2–mediated PI3-kinase activation coordinates reactivation of quiescent neuroblasts with growth of their glial stem cell niche

PLoS Biology, Journal Year: 2020, Volume and Issue: 18(5), P. e3000721 - e3000721

Published: May 28, 2020

Dietary nutrients provide macromolecules necessary for organism growth and development. In response to animal feeding, evolutionarily conserved signaling pathways are activated, leading increased rates of cell proliferation tissue growth. It remains unclear how different types within developing tissues coordinate in dietary whether coordinated is proper function. Using the early Drosophila larval brain, we asked nutrient-dependent neural stem cells (neuroblasts), glia, trachea among these major brain required known that PI3-kinase activation, ventral nerve cord neuroblasts reactivate from quiescence glia expand their membranes. Here, assay a cell-type specific manner at short time intervals determine mediated part through activation signaling. Of 7 insulin-like peptides (Dilps), find Dilp-2 coordination between brain. induces cortex initiate membrane make first contact with quiescent neuroblasts. Once reactivated, promote ultimately form selective barrier. Our results highlight importance bidirectional surrounding nutrition demonstrate drives morphogenesis

Language: Английский

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Drosophila glia take shape to sculpt the nervous system

Current Opinion in Neurobiology, Journal Year: 2023, Volume and Issue: 79, P. 102689 - 102689

Published: Feb. 22, 2023

Language: Английский

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