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Drosophila synapse and glia

Giulia Romano, Nikola Holodkov, Raffaella Klima, Federica Grilli, Corrado Guarnaccia, Monica Nizzardo, Federica Rizzo, Rodolfo Garcia, Fabian Feiguin
Amyotrophic lateral sclerosis is a progressive neurodegenerative disease that affects the motor system, comprised of motoneurons and associated glia. Accordingly, neuronal or glial defects in TDP-43 function provoke paralysis due to the degeneration of the neuromuscular synapses in Drosophila. To identify the responsible molecules and mechanisms, we performed a genome wide proteomic analysis to determine differences in protein expression between wild-type and TDP-43-minus fly heads. The data established that mutant insects presented reduced levels of the enzyme glutamic acid decarboxylase (Gad1) and increased concentrations of extracellular glutamate...
January 29, 2018: Scientific Reports
Joshua S Titlow, Lu Yang, Richard M Parton, Ana Palanca, Ilan Davis
The lack of an effective, simple, and highly sensitive protocol for fluorescent in situ hybridization (FISH) at the Drosophila larval neuromuscular junction (NMJ) has hampered the study of mRNA biology. Here, we describe our modified single molecule FISH (smFISH) methods that work well in whole mount Drosophila NMJ preparations to quantify primary transcription and count individual cytoplasmic mRNA molecules in specimens while maintaining ultrastructural preservation. The smFISH method is suitable for high-throughput sample processing and 3D image acquisition using any conventional microscopy imaging modality and is compatible with the use of antibody colabeling and transgenic fluorescent protein tags in axons, glia, synapses, and muscle cells...
2018: Methods in Molecular Biology
Melissa Borgen, Kimberly Rowland, Jana Boerner, Brandon Lloyd, Aruna Khan, Rodney Murphey
The ubiquitin ligase Highwire has a conserved role in synapse formation. Here, we show that Highwire coordinates several facets of central synapse formation in the Drosophila melanogaster giant fiber system, including axon termination, axon pruning, and synaptic function. Despite the similarities to the fly neuromuscular junction, the role of Highwire and the underlying signaling pathways are distinct in the fly's giant fiber system. During development, branching of the giant fiber presynaptic terminal occurs and, normally, the transient branches are pruned away...
March 2017: Genetics
Sarah E MacNamee, Kendra E Liu, Stephan Gerhard, Cathy T Tran, Richard D Fetter, Albert Cardona, Leslie P Tolbert, Lynne A Oland
Anatomical, molecular, and physiological interactions between astrocytes and neuronal synapses regulate information processing in the brain. The fruit fly Drosophila melanogaster has become a valuable experimental system for genetic manipulation of the nervous system and has enormous potential for elucidating mechanisms that mediate neuron-glia interactions. Here, we show the first electrophysiological recordings from Drosophila astrocytes and characterize their spatial and physiological relationship with particular synapses...
July 1, 2016: Journal of Comparative Neurology
Jiayao Ou, Zongbao Gao, Li Song, Margaret S Ho
Neurons and glia are the two major cell types in the nervous system and work closely with each other to program neuronal interplay. Traditionally, neurons are thought to be the major cells that actively regulate processes like synapse formation, plasticity, and behavioral output. Glia, on the other hand, serve a more supporting role. To date, accumulating evidence has suggested that glia are active participants in virtually every aspect of neuronal function. Despite this, fundamental features of how glia interact with neurons, and their spatial relationships, remain elusive...
April 2016: Neuroscience Bulletin
Alexandra L Strauss, Fumiko Kawasaki, Richard W Ordway
Previous studies of Drosophila flight muscle neuromuscular synapses have revealed their tripartite architecture and established an attractive experimental model for genetic analysis of glial function in synaptic transmission. Here we extend these findings by defining a new Drosophila glial cell type, designated peripheral perisynaptic glia (PPG), which resides in the periphery and interacts specifically with fine motor axon branches forming neuromuscular synapses. Identification and specific labeling of PPG was achieved through cell type-specific RNAi-mediated knockdown (KD) of a glial marker, Glutamine Synthetase 2 (GS2)...
2015: PloS One
Motomi Matsuno, Junjiro Horiuchi, Yoshihiro Yuasa, Kyoko Ofusa, Tomoyuki Miyashita, Tomoko Masuda, Minoru Saitoe
Long-term memory (LTM) formation requires de novo gene expression in neurons, and subsequent structural and functional modification of synapses. However, the importance of gene expression in glia during this process has not been well studied. In this report, we characterize a cell adhesion molecule, Klingon (Klg), which is required for LTM formation in Drosophila. We found that Klg localizes to the juncture between neurons and glia, and expression in both cell types is required for LTM. We further found that expression of a glial gene, repo, is reduced in klg mutants and knockdown lines...
April 8, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Jaison Jiro Omoto, Puja Yogi, Volker Hartenstein
Glia comprise a conspicuous population of non-neuronal cells in vertebrate and invertebrate nervous systems. Drosophila serves as a favorable model to elucidate basic principles of glial biology in vivo. The Drosophila neuropil glia (NPG), subdivided into astrocyte-like (ALG) and ensheathing glia (EG), extend reticular processes which associate with synapses and sheath-like processes which surround neuropil compartments, respectively. In this paper we characterize the development of NPG throughout fly brain development...
August 15, 2015: Developmental Biology
Choong H Lee, Stephen J Blackband, Pedro Fernandez-Funez
Understanding the complex architecture, connectivity, and pathology of the human brain is a major application of magnetic resonance imaging (MRI). However, the cellular basis of MR signal is still poorly understood. The advent of MR microscopy (MRM) enables imaging biological samples at cellular resolution, helping to interpret the nature of MR signal at the cellular level. In this regard, the small Drosophila brain can reveal key aspects of MR signal through the visualization of complex, intact neuronal structures in their native spatial arrangement...
2015: Scientific Reports
Marc R Freeman
Molecular genetic approaches in small model organisms like Drosophila have helped to elucidate fundamental principles of neuronal cell biology. Much less is understood about glial cells, although interest in using invertebrate preparations to define their in vivo functions has increased significantly in recent years. This review focuses on our current understanding of the three major neuron-associated glial cell types found in the Drosophila central nervous system (CNS)-astrocytes, cortex glia, and ensheathing glia...
February 26, 2015: Cold Spring Harbor Perspectives in Biology
Minoru Nakayama, Fumiya Matsushita, Chihiro Hama
The synaptic cleft, a crucial space involved in neurotransmission, is filled with extracellular matrix that serves as a scaffold for synaptic differentiation. However, little is known about the proteins present in the matrix and their functions in synaptogenesis, especially in the CNS. Here, we report that Hikaru genki (Hig), a secreted protein with an Ig motif and complement control protein domains, localizes specifically to the synaptic clefts of cholinergic synapses in the Drosophila CNS. The data indicate that this specific localization is achieved by capture of secreted Hig in synaptic clefts, even when it is ectopically expressed in glia...
October 15, 2014: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Tobias Stork, Amy Sheehan, Ozge E Tasdemir-Yilmaz, Marc R Freeman
Astrocytes are critically important for neuronal circuit assembly and function. Mammalian protoplasmic astrocytes develop a dense ramified meshwork of cellular processes to form intimate contacts with neuronal cell bodies, neurites, and synapses. This close neuron-glia morphological relationship is essential for astrocyte function, but it remains unclear how astrocytes establish their intricate morphology, organize spatial domains, and associate with neurons and synapses in vivo. Here we characterize a Drosophila glial subtype that shows striking morphological and functional similarities to mammalian astrocytes...
July 16, 2014: Neuron
Jiayao Ou, Yijing He, Xi Xiao, Tian-Ming Yu, Changyan Chen, Zongbao Gao, Margaret S Ho
Glia outnumber neurons and are the most abundant cell type in the nervous system. Whereas neurons are the major carriers, transducers, and processors of information, glial cells, once considered mainly to play a passive supporting role, are now recognized for their active contributions to almost every aspect of nervous system development. Recently, insights from the invertebrate organism Drosophila melanogaster have advanced our knowledge of glial cell biology. In particular, findings on neuron-glia interactions via intrinsic and extrinsic mechanisms have shed light on the importance of glia during different stages of neuronal development...
August 2014: Neuroscience Bulletin
He Liu, Bangyu Zhou, Wenjun Yan, Zhengchang Lei, Xiaoliang Zhao, Ke Zhang, Aike Guo
Astrocyte-like glial cells are abundant in the central nervous system of adult Drosophila and exhibit morphology similar to astrocytes of mammals. Previous evidence has shown that astrocyte-like glial cells are strongly associated with synapses in the antennal lobe (AL), the first relay of the olfactory system, where olfactory receptor neurons (ORNs) transmit information into projection neurons (PNs). However, the function of astrocyte-like glia in the AL remains obscure. In this study, using in vivo calcium imaging, we found that astrocyte-like glial cells exhibited spontaneous microdomain calcium elevations...
September 2014: European Journal of Neuroscience
Ozge E Tasdemir-Yilmaz, Marc R Freeman
Precise neural circuit assembly is achieved by initial overproduction of neurons and synapses, followed by refinement through elimination of exuberant neurons and synapses. Glial cells are the primary cells responsible for clearing neuronal debris, but the cellular and molecular basis of glial pruning is poorly defined. Here we show that Drosophila larval astrocytes transform into phagocytes through activation of a cell-autonomous, steroid-dependent program at the initiation of metamorphosis and are the primary phagocytic cell type in the pupal neuropil...
January 1, 2014: Genes & Development
Megan M Corty, Marc R Freeman
Glia serve many important functions in the mature nervous system. In addition, these diverse cells have emerged as essential participants in nearly all aspects of neural development. Improved techniques to study neurons in the absence of glia, and to visualize and manipulate glia in vivo, have greatly expanded our knowledge of glial biology and neuron-glia interactions during development. Exciting studies in the last decade have begun to identify the cellular and molecular mechanisms by which glia exert control over neuronal circuit formation...
November 11, 2013: Journal of Cell Biology
Patricia S Estes, Scott G Daniel, Abigail P McCallum, Ashley V Boehringer, Alona S Sukhina, Rebecca A Zwick, Daniela C Zarnescu
Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by complex neuronal and glial phenotypes. Recently, RNA-based mechanisms have been linked to ALS via RNA-binding proteins such as TDP-43, which has been studied in vivo using models ranging from yeast to rodents. We have developed a Drosophila model of ALS based on TDP-43 that recapitulates several aspects of pathology, including motor neuron loss, locomotor dysfunction and reduced survival. Here we report the phenotypic consequences of expressing wild-type and four different ALS-linked TDP-43 mutations in neurons and glia...
May 2013: Disease Models & Mechanisms
E A Nikitina, A V Medvedeva, Iu F Dolgaia, L I Korochkin, G V Pavlova, E V Savvateeva-Popova
Molecular mechanisms of the synapse and dendrite maintenance and their disturbance in psychiatric and neurodegenerative diseases (ND) are intensively studied in searching for target genes of therapeutic actions. It is suggested that glia, alongside with well-studied pre- and postsynaptic neurons, is the third, poorly studied partner in synaptic transmission (the tripartite synapse) that is involved in the positive feedback between the first two partners. This bidirectional coupling between presynaptic neurons and their postsynaptic targets involve neurotrophins (NTF), such as glial cell-derived neurotrophic factor (GDNF) that is produced LIM kinase 1 (LIMK1, the key enzyme of actin remodeling)...
November 2012: Zhurnal Evoliutsionno─ş Biokhimii i Fiziologii
Petia Kupenova, Shazie Yusein-Myashkova
PURPOSE: Histaminergic transmission in the first synapse of the visual system in Drosophila melanogaster is mediated by two types of histamine receptors: 1) encoded by the gene hclA (HCLA), which is expressed in the second-order neurons-the large monopolar cells of the lamina, and is absolutely required for forward signal transmission; and 2) encoded by the gene hclB (HCLB), which is expressed in epithelial glia, and is involved in modulation of synaptic transmission from photoreceptors to large monopolar cells...
2012: Molecular Vision
Allison Rosen Bialas, Beth Stevens
Glia cells are uniquely positioned at synapses, contacting pre- and post-synaptic terminals. At the Drosophila neuromuscular junction, a novel glia-derived TGF-╬▓ ligand has been found that modulates a retrograde synaptogenic signal.
October 9, 2012: Current Biology: CB
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