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Autophagy is an important process that maintains adult tissue homeostasis and functions by protecting cells in autonomous and non-cell-autonomous ways. By degrading toxic components or proteins involved in cell signaling pathways, autophagy preserves the balance among stem cells, progenitors, and differentiated cells in various tissues. In this minireview, we discuss recent studies performed in Drosophila that highlight new roles of autophagy in adult cell fate decisions, including quiescence, proliferation, differentiation, and death. Key words: autophagy, Drosophila, adult stem cells, differentiated cells, mitophagy, cell fate, homeostasis L'autophagie joue un role important dans le maintien de l'homeostasie et la fonction des tissus chez l'adulte en protegeant les cellules directement ou indirectement. En degradant les composes toxiques ou les proteines impliquees dans des voies de signalisation, l'autophagie preserve la balance entre les cellules souches, progenitrices et diferenciees dans diferents tissus. Dans cette mini-revue, seront discutees les etudes recentes effectuees chez la drosophile qui mettent en evidence des nou-veaux roles de l'autophagie dans le devenir de la cellule adulte, a savoir: la quiescence, la proliferation, la diferenciation et la mort. Mots-cles : autophagie, drosophile, cellules souches adultes, cellules diferenciees, mitophagie, destin cellulaire, homeostasie, Introduction Under homeostatic and stress conditions, the conserved catabolic process of autophagy, defined as lysosomal degradation of cellular constituents, plays a key role in tissue homeostasis, which we refer to [...]

Phenotypic plasticity has been described for morphological and life-history traits in many organisms. In Drosophila, temperature drives phenotypic change in several traits, but few Neotropical species have been studied and whether the phenotypic variation associated with plasticity is adaptive remains unclear. Here, we studied the phenotypic response to temperature variation in the distantly related Neotropical species Drosophila mercatorum Patterson and Wheeler, 1942 and Drosophila willistoni Sturtevant, 1916. We evaluate if wing shape variation follows that observed in the Neotropical species Drosophila cardini Sturtevant, 1916: round wings at lower temperatures and narrower wings at higher temperatures. The variation in egg-adult development time and in wing size, shape, and allometry was described using reaction norms and geometric morphometrics. In both species, development time and wing size decreased with increasing temperature and wing allometry showed that size explained [approximately equal to]10% of the shape variation. Wing shape, however, exhibited contrasting responses. At higher temperatures, D. mercatorum developed slightly slender wings, following the pattern previously found for D. cardini, whereas D. willistoni developed plumper and shorter wings, supporting previous studies on Drosophila melanogaster Meigen, 1830. We conclude that all traits studied here were influenced by temperature, and that wing shape seems also to be influenced by phylogeny. Key words: Cerrado, Drosophila mercatorum, Drosophila willistoni, egg-adult development time, geometric morphometrics, Sophophora, wing size, wing shape. Une plasticité phénotypique a été décrite pour des caractères morphologiques et du cycle biologique chez de nombreux organismes. Si, chez les Drosophila, la température induit des changements phénotypiques de plusieurs caractères, peu d'espèces néotropicales ont été étudiées, et il n'est pas encore bien établi que les variations phénotypiques associées à la plasticité sont adaptatives. Nous avons étudié la réaction phénotypique aux variations de température chez Drosophila mercatorum Patterson et Wheeler, 1942, et Drosophila willistoni Sturtevant, 1916, des espèces néotropicales apparentées de loin. Nous évaluons si les variations de la forme des ailes suivent les variations observées chez l'espèce néotropicale Drosophila cardini Sturtevant, 1916, à savoir des ailes arrondies à plus faibles températures et des ailes plus étroites à plus hautes températures. Les variations de la durée du développement de l'ceuf au stade adulte et de la taille, de la forme et de l'allométrie des ailes sont décrites à l'aide de normes de réaction et de la morphométrie géométrique. Chez les deux espèces, la durée du développement et la taille des ailes diminuent quand la température augmente et l'allométrie des ailes montre que la taille explique [approximately equal to]10 % des variations de la forme des ailes. Cette dernière présente toutefois des réactions variées. À plus hautes températures, les ailes de D. mercatorum sont légèrement élancées, suivant un motif observé précédemment chez D. cardini, alors que les ailes de D. willistoni sont plus arrondies et courtes, ce qui appuie les résultats d'études antérieures portant sur Drosophila melanogaster Meigen, 1830. Nous concluons que la température influence tous les caractères étudiés et que la phylogénie semble aussi influencer la forme des ailes. [Traduit par la Rédaction] Mots-clés : Cerrado, Drosophila mercatorum, Drosophila willistoni, durée du développement de l'ceuf au stade adulte, morphométrie géométrique, Sophophora, taille des ailes, forme des ailes., Introduction Phenotypic plasticity is the ability of a single genotype to produce different phenotypes in response to environmental variation (Pigliucci 2001). This phenomenon can produce adaptive variation by adjusting the [...]

During sleep, most animal species enter a state of reduced consciousness characterized by a marked sensory disconnect. Yet some processing of the external world must remain intact, given that a sleeping animal can be awoken by intense stimuli (for example, a loud noise or a bright light) or by soft but qualitatively salient stimuli (for example, the sound of a baby cooing or hearing one's own name.sup.1-3). How does a sleeping brain retain the ability to process the quality of sensory information? Here we present a paradigm to study the functional underpinnings of sensory discrimination during sleep in Drosophila melanogaster. We show that sleeping vinegar flies, like humans, discern the quality of sensory stimuli and are more likely to wake up in response to salient stimuli. We also show that the salience of a stimulus during sleep can be modulated by internal states. We offer a prototypical blueprint detailing a circuit involved in this process and its modulation as evidence that the system can be used to explore the cellular underpinnings of how a sleeping brain experiences the world. The authors develop a paradigm to study sensory discrimination during sleep in Drosophila melanogaster., Author(s): Alice S. French [sup.1] , Quentin Geissmann [sup.2] , Esteban J. Beckwith [sup.3] , Giorgio F. Gilestro [sup.1] Author Affiliations: (1) Department of Life Sciences, Imperial College London, London, [...]

A balanced intake of macronutrients--protein, carbohydrate and fat--is essential for the well-being of organisms. An adequate calorific intake but with insufficient protein consumption can lead to several ailments, including kwashiorkor.sup.1. Taste receptors (T1R1-T1R3).sup.2 can detect amino acids in the environment, and cellular sensors (Gcn2 and Tor).sup.3 monitor the levels of amino acids in the cell. When deprived of dietary protein, animals select a food source that contains a greater proportion of protein or essential amino acids (EAAs).sup.4. This suggests that food selection is geared towards achieving the target amount of a particular macronutrient with assistance of the EAA-specific hunger-driven response, which is poorly understood. Here we show in Drosophila that a microbiome-gut-brain axis detects a deficit of EAAs and stimulates a compensatory appetite for EAAs. We found that the neuropeptide CNMamide (CNMa).sup.5 was highly induced in enterocytes of the anterior midgut during protein deprivation. Silencing of the CNMa-CNMa receptor axis blocked the EAA-specific hunger-driven response in deprived flies. Furthermore, gnotobiotic flies bearing an EAA-producing symbiotic microbiome exhibited a reduced appetite for EAAs. By contrast, gnotobiotic flies with a mutant microbiome that did not produce leucine or other EAAs showed higher expression of CNMa and a greater compensatory appetite for EAAs. We propose that gut enterocytes sense the levels of diet- and microbiome-derived EAAs and communicate the EAA-deprived condition to the brain through CNMa. In Drosophila, an amino acid deficit triggers the expression of the neuropeptide CNMamide in gut enterocytes, which promotes a compensatory appetite for essential over non-essential amino acids, and this process is modulated by the microbiome., Author(s): Boram Kim [sup.1] [sup.2] , Makoto I. Kanai [sup.3] , Yangkyun Oh [sup.3] , Minsoo Kyung [sup.1] , Eun-Kyoung Kim [sup.1] , In-Hwan Jang [sup.1] , Ji-Hoon Lee [sup.1] [...]

Critical periods--brief intervals during which neural circuits can be modified by activity--are necessary for proper neural circuit assembly. Extended critical periods are associated with neurodevelopmental disorders; however, the mechanisms that ensure timely critical period closure remain poorly understood.sup.1,2. Here we define a critical period in a developing Drosophila motor circuit and identify astrocytes as essential for proper critical period termination. During the critical period, changes in activity regulate dendrite length, complexity and connectivity of motor neurons. Astrocytes invaded the neuropil just before critical period closure.sup.3, and astrocyte ablation prolonged the critical period. Finally, we used a genetic screen to identify astrocyte-motor neuron signalling pathways that close the critical period, including Neuroligin-Neurexin signalling. Reduced signalling destabilized dendritic microtubules, increased dendrite dynamicity and impaired locomotor behaviour, underscoring the importance of critical period closure. Previous work defined astroglia as regulators of plasticity at individual synapses.sup.4; we show here that astrocytes also regulate motor circuit critical period closure to ensure proper locomotor behaviour. The duration of a critical period of plasticity in the developing Drosophila motor circuit, during which motor neurons display activity-dependent refinement of neurite structure and connectivity, is dependent on astrocyte to motor neuron Neuroligin-Neurexin signalling., Author(s): Sarah D. Ackerman [sup.1] , Nelson A. Perez-Catalan [sup.1] [sup.3] , Marc R. Freeman [sup.2] , Chris Q. Doe [sup.1] Author Affiliations: (1) Institute of Neuroscience, Howard Hughes Medical [...]

Many studies require the ability to quantify locomotor behavior over time. The list of tracking softwares and their capabilities are constantly growing. At the 2019 CanFly Conference, we presented preliminary results from an investigation of the effects of expressing polyglutamine repeats in fly muscles on longevity, locomotion, and protein aggregation. Numerous requests have been received regarding our protocol to measure locomotion and how to use the FlyTracker MatLab software. This report describes a versatile locomotion measuring device and custom MatLab scripts for the extraction, analysis, and compilation of FlyTracker data in a format compatible with spreadsheet softwares. The measurement and analysis of multiple genotypes of both sexes across age demonstrates that this method yields reproducible results that confirm that normal aging is associated with a progressive decline in locomotion as indicated by increased immobility and reduced velocity. Key words: behavior, FlyTracker, MatLab, aging, Drosophila melanogaster. Plusieurs etudes necessitent la capacite de quantifier le comportement locomoteur dans le temps. La liste des logiciels de suivi des mouvements et leurs capacites sont en constante evolution. Lors de la conference CanFly 2019, les auteurs ont presente les resultats preliminaires d'une etude sur les effets de l'expression de repetitions polyglutaminiques dans les muscles des mouches sur leur longevite, leur locomotion et l'agregation des proteines. De nombreuses demandes ont ete recues au sujet du protocole employe pour mesurer la locomotion et sur l'emploi du logiciel MatLab FlyTracker. Cet article decrit un appareil polyvalent de mesure de la locomotion ainsi que des scripts MatLab ecrits sur mesure et concus pour extraire, analyser et compiler les donnees de FlyTracker en une forme qui soit compatible avec des tableurs. La mesure et l'analyse de multiples genotypes des deux sexes au cours de leur vie demontre que cette methode produit des resultats reproductibles et confirme que le vieillissement normal est associe a un declin progressif de la locomotion, tel qu'indique par une immobilite accrue et une vitesse reduite. [Traduit par la Redaction] Mots-cles : comportement, FlyTracker, MatLab, vieillissement, Drosophila melanogaster., Introduction Locomotion is a fundamental behavioral trait involved directly or indirectly with almost all simple or complex behavior activities. It is also integral to studying a wide span of different [...]

Peroxisomes are organelles in eukaryotic cells responsible for processing several types of lipids and management of reactive oxygen species. A conserved family of peroxisome biogenesis (Peroxin, Pex) genes encode proteins essential to peroxisome biogenesis or function. In yeast and mammals, PEROXIN7 (PEX7) acts as a cytosolic receptor protein that targets enzymes containing a peroxisome targeting signal 2 (PTS2) motif for peroxisome matrix import. The PTS2 motif is not present in the Drosophila melanogaster homologs of these enzymes. However, the fly genome contains a Pex7 gene (CG6486) that is very similar to yeast and human PEX7. We find that Pex7 is expressed in tissue-specific patterns analogous to differentiating neuroblasts in D. melanogaster embryos. This is correlated with a requirement for Pex7 in this cell lineage as targeted somatic Pex7 knockout in embryonic neuroblasts reduced survival. We also found that Pex7 over-expression in the same cell lineages caused lethality during the larval stage. Targeted somatic over-expression of a Pex7 transgene in neuroblasts of Pex7 homozygous null mutants resulted in a semi-lethal phenotype similar to targeted Pex7 knockout. These findings suggest that D. melanogaster has tissue-specific requirements for Pex7 during embryo development. Keywords: peroxisomes, Peroxin 7, Drosophila melanogaster, embryogenesis, CRISPR-TRiP-KO. Les peroxysomes sont des organites dans les cellules eucaryotes qui sont responsables du traitement de plusieurs lipides et de la gestion des radicaux libres. Une famille conservee de genes impliques dans la genese des peroxysomes (Peroxin, Pex) code pour des proteines essentielles a la biogenese ou a la fonction des peroxysomes. Chez la levure et les mammiferes, PEROXIN7 (PEX7) est une proteine qui agit comme recepteur cytosolique pour les enzymes contenant un motif signal peroxysomique 2 (PTS2) qui assure leur importation dans la matrice du peroxysome. Le motif PTS2 est absent chez les homologues de ces enzymes chez le Drosophila melanogaster. Cepen-dant, le genome de la drosophile contient un gene Pex7 (CG6486) qui est tres semblable a PEX7 chez la levure et l'humain. Les auteurs trouvent que Pex7 est exprime dans les tissus correspondants aux neuroblastes en cours de differenciation chez les embryons du D. melanogaster. Ceci est correle avec la necessite de Pex7 au sein de ces cellules car une inactivation ciblee de Pex7 chez les neuroblastes a reduit la survie des embryons. Les auteurs ont egalement trouve qu'une sur-expression au sein des memes cellules cause la letalite au cours du stade larvaire. Une sur-expression somatique ciblee d'un transgene Pex7 chez les neuroblastes de mutants nulls homozygotes Pex7 entraine une semi-letalite semblable a l'inactivation ciblee de Pex7. Ces resultats suggerent qu'il existe des exigences en matiere de specificite tissulaire pour Pex7 au cours du developpement embryonnaire chez le D. melanogaster. [Traduit par la Redaction] Mots-cles : peroxysomes, Peroxin 7, Drosophila melanogaster, embryogenese, CRISPR-TRiP-KO., Introduction Peroxisomes are organelles found in most eukaryotic cells. Their role varies by organism, with a core functionality of fatty acid [beta]-oxidation and detoxification of reactive oxygen species. In fungi [...]

Nuclear-cytoplasmic localization is an efficient way to regulate transcription factors and chromatin remodelers. Altering the location of existing protein pools also facilitates a more rapid response to changes in cell activity or extracellular signals. There are several examples of proteins that are regulated by nucleo-cytoplasmic shuttling, which are required for Drosophila neuroblast development. Disruption of the localization of homologs of these proteins has also been linked to several neurodegenerative disorders in humans. Drosophila has been used extensively to model the neurodegenerative disorders caused by aberrant nucleo-cytoplasmic localization. Here, we focus on the role of alternative nucleo-cytoplasmic protein localization in regulating proliferation and cell fate decisions in the Drosophila neuroblast and in neurodegenerative disorders. We also explore the analogous role of RNA binding proteins and mRNA localization in the context of regulation of nucleo-cytoplasmic localization during neural development and a role in neurodegenerative disorders. Key words: Drosophila melanogaster, nucleo-cytoplasmic transport, neuroblast, nervous system, neurodegenerative disorder, localization. La localisation nucleo-cytoplasmique est un moyen efficient pour reguler les facteurs de transcription et les remodeleurs de la chromatine. Alterer la localisation de pools proteiques existants facilite egalement une reponse plus rapide aux changements dans l'activite cellulaire ou aux signaux extracellulaires. Il y a plusieurs exemples de proteines qui sont regulees par le transport nucleo-cytoplasmique, lequel est requis pour le developpement des neuroblastes chez la drosophile. Une perturbation de la localisation des homologues de ces proteines chez les humains a ete liee a de nombreux troubles neurodegeneratifs. La drosophile a ete employee de maniere importante pour modeliser les desordres neurodegeneratifs causes par une localisation nucleocytoplasmique aberrante. Dans ce travail, les auteurs etudient le role d'une localisation nucleo-cytoplasmique alternative dans la regulation de la proliferation et du devenir des cellules chez les neuroblastes de la drosophile et dans les desordres neurodegeneratifs. Ils explorent egalement les roles analogues des proteines de liaison a l'ARN et de la localisation des ARNm dans le contexte de la regulation de la localisation nucleo-cytoplasmique au cours du developpement et de leur role dans les desordres neurodegeneratifs. [Traduit par la Redaction] Mots-cles : Drosophila melanogaster, transport nucleo-cytoplasmique, neuroblaste, systeme nerveux, desordres neurodegeneratifs, localisation., Introduction The nuclear membrane is a complex barrier surrounding the chromatin. It is pierced by nuclear pores that function as gatekeepers of nucleo-cytoplasmic transport. Molecules of smaller size can diffuse [...]

Sexual dimorphism arises from genetic differences between male and female cells, and from systemic hormonal differences.sup.1-3. How sex hormones affect non-reproductive organs is poorly understood, yet highly relevant to health given the sex-biased incidence of many diseases.sup.4. Here we report that steroid signalling in Drosophila from the ovaries to the gut promotes growth of the intestine specifically in mated females, and enhances their reproductive output. The active ovaries of the fly produce the steroid hormone ecdysone, which stimulates the division and expansion of intestinal stem cells in two distinct proliferative phases via the steroid receptors EcR and Usp and their downstream targets Broad, Eip75B and Hr3. Although ecdysone-dependent growth of the female gut augments fecundity, the more active and more numerous intestinal stem cells also increase female susceptibility to age-dependent gut dysplasia and tumorigenesis, thus potentially reducing lifespan. This work highlights the trade-offs in fitness traits that occur when inter-organ signalling alters stem-cell behaviour to optimize organ size. High levels of the sexually dimorphic hormone ecdysone, produced by active ovaries in Drosophila, promote the proliferation of stem cells in the female gut and maximize reproductive fitness, but also increase female susceptibility to age-dependent dysplasia and tumorigenesis., Author(s): Sara Mahmoud H. Ahmed [sup.1] [sup.2] [sup.3] , Julieta A. Maldera [sup.1] [sup.2] , Damir Krunic [sup.1] , Gabriela O. Paiva-Silva [sup.4] , Clothilde Pénalva [sup.5] , Aurelio A. [...]

Although glucose-sensing neurons were identified more than 50 years ago, the physiological role of glucose sensing in metazoans remains unclear. Here we identify a pair of glucose-sensing neurons with bifurcated axons in the brain of Drosophila. One axon branch projects to insulin-producing cells to trigger the release of Drosophila insulin-like peptide 2 (dilp2) and the other extends to adipokinetic hormone (AKH)-producing cells to inhibit secretion of AKH, the fly analogue of glucagon. These axonal branches undergo synaptic remodelling in response to changes in their internal energy status. Silencing of these glucose-sensing neurons largely disabled the response of insulin-producing cells to glucose and dilp2 secretion, disinhibited AKH secretion in corpora cardiaca and caused hyperglycaemia, a hallmark feature of diabetes mellitus. We propose that these glucose-sensing neurons maintain glucose homeostasis by promoting the secretion of dilp2 and suppressing the release of AKH when haemolymph glucose levels are high. A pair of glucose-sensing neurons identified in the brain of Drosophila melanogaster regulates secretion of adipokinetic hormone and Drosophila insulin-like peptide 2, suggesting that these neurons have key roles in maintenance of glucose homeostasis., Author(s): Yangkyun Oh [sup.1] , Jason Sih-Yu Lai [sup.1] [sup.2] , Holly J. Mills [sup.1] [sup.3] , Hediye Erdjument-Bromage [sup.1] , Benno Giammarinaro [sup.1] [sup.4] , Khalil Saadipour [sup.1] , [...]

While research into the biology of animal behaviour has primarily focused on the central nervous system, cues from peripheral tissues and the environment have been implicated in brain development and function.sup.1. There is emerging evidence that bidirectional communication between the gut and the brain affects behaviours including anxiety, cognition, nociception and social interaction.sup.1-9. Coordinated locomotor behaviour is critical for the survival and propagation of animals, and is regulated by internal and external sensory inputs.sup.10,11. However, little is known about how the gut microbiome influences host locomotion, or the molecular and cellular mechanisms involved. Here we report that germ-free status or antibiotic treatment results in hyperactive locomotor behaviour in the fruit fly Drosophila melanogaster. Increased walking speed and daily activity in the absence of a gut microbiome are rescued by mono-colonization with specific bacteria, including the fly commensal Lactobacillus brevis. The bacterial enzyme xylose isomerase from L. brevis recapitulates the locomotor effects of microbial colonization by modulating sugar metabolism in flies. Notably, thermogenetic activation of octopaminergic neurons or exogenous administration of octopamine, the invertebrate counterpart of noradrenaline, abrogates the effects of xylose isomerase on Drosophila locomotion. These findings reveal a previously unappreciated role for the gut microbiome in modulating locomotion, and identify octopaminergic neurons as mediators of peripheral microbial cues that regulate motor behaviour in animals.Female Drosophila that lack a microbiota are hyperactive, and xylose isomerase from Lactobacillus brevis is sufficient to reverse this effect., Author(s): Catherine E. Schretter [sup.1] , Jost Vielmetter [sup.2] , Imre Bartos [sup.3] , Zsuzsa Marka [sup.3] , Szabolcs Marka [sup.3] , Sulabha Argade [sup.4] , Sarkis K. Mazmanian [sup.1] [...]