48 results on '"Gaia Tavosanis"'
Search Results
2. The anterior paired lateral neuron normalizes odour-evoked activity in the Drosophila mushroom body calyx
- Author
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Luigi Prisco, Stephan Hubertus Deimel, Hanna Yeliseyeva, André Fiala, and Gaia Tavosanis
- Subjects
mushroom body ,APL ,microglomerulus ,sparse coding ,inhibition ,pattern separation ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
To identify and memorize discrete but similar environmental inputs, the brain needs to distinguish between subtle differences of activity patterns in defined neuronal populations. The Kenyon cells (KCs) of the Drosophila adult mushroom body (MB) respond sparsely to complex olfactory input, a property that is thought to support stimuli discrimination in the MB. To understand how this property emerges, we investigated the role of the inhibitory anterior paired lateral (APL) neuron in the input circuit of the MB, the calyx. Within the calyx, presynaptic boutons of projection neurons (PNs) form large synaptic microglomeruli (MGs) with dendrites of postsynaptic KCs. Combining electron microscopy (EM) data analysis and in vivo calcium imaging, we show that APL, via inhibitory and reciprocal synapses targeting both PN boutons and KC dendrites, normalizes odour-evoked representations in MGs of the calyx. APL response scales with the PN input strength and is regionalized around PN input distribution. Our data indicate that the formation of a sparse code by the KCs requires APL-driven normalization of their MG postsynaptic responses. This work provides experimental insights on how inhibition shapes sensory information representation in a higher brain centre, thereby supporting stimuli discrimination and allowing for efficient associative memory formation.
- Published
- 2021
- Full Text
- View/download PDF
3. Achieving functional neuronal dendrite structure through sequential stochastic growth and retraction
- Author
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André Ferreira Castro, Lothar Baltruschat, Tomke Stürner, Amirhoushang Bahrami, Peter Jedlicka, Gaia Tavosanis, and Hermann Cuntz
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dendrite function ,dendrite growth ,dendrite retraction ,mechanotransduction ,self-organisation ,computer model ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Class I ventral posterior dendritic arborisation (c1vpda) proprioceptive sensory neurons respond to contractions in the Drosophila larval body wall during crawling. Their dendritic branches run along the direction of contraction, possibly a functional requirement to maximise membrane curvature during crawling contractions. Although the molecular machinery of dendritic patterning in c1vpda has been extensively studied, the process leading to the precise elaboration of their comb-like shapes remains elusive. Here, to link dendrite shape with its proprioceptive role, we performed long-term, non-invasive, in vivo time-lapse imaging of c1vpda embryonic and larval morphogenesis to reveal a sequence of differentiation stages. We combined computer models and dendritic branch dynamics tracking to propose that distinct sequential phases of stochastic growth and retraction achieve efficient dendritic trees both in terms of wire and function. Our study shows how dendrite growth balances structure–function requirements, shedding new light on general principles of self-organisation in functionally specialised dendrites.
- Published
- 2020
- Full Text
- View/download PDF
4. Modulators of hormonal response regulate temporal fate specification in the Drosophila brain.
- Author
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Giovanni Marchetti and Gaia Tavosanis
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Genetics ,QH426-470 - Abstract
Neuronal diversity is at the core of the complex processing operated by the nervous system supporting fundamental functions such as sensory perception, motor control or memory formation. A small number of progenitors guarantee the production of this neuronal diversity, with each progenitor giving origin to different neuronal types over time. How a progenitor sequentially produces neurons of different fates and the impact of extrinsic signals conveying information about developmental progress or environmental conditions on this process represent key, but elusive questions. Each of the four progenitors of the Drosophila mushroom body (MB) sequentially gives rise to the MB neuron subtypes. The temporal fate determination pattern of MB neurons can be influenced by extrinsic cues, conveyed by the steroid hormone ecdysone. Here, we show that the activation of Transforming Growth Factor-β (TGF-β) signalling via glial-derived Myoglianin regulates the fate transition between the early-born α'β' and the pioneer αβ MB neurons by promoting the expression of the ecdysone receptor B1 isoform (EcR-B1). While TGF-β signalling is required in MB neuronal progenitors to promote the expression of EcR-B1, ecdysone signalling acts postmitotically to consolidate theα'β' MB fate. Indeed, we propose that if these signalling cascades are impaired α'β' neurons lose their fate and convert to pioneer αβ. Conversely, an intrinsic signal conducted by the zinc finger transcription factor Krüppel-homolog 1 (Kr-h1) antagonises TGF-β signalling and acts as negative regulator of the response mediated by ecdysone in promoting α'β' MB neuron fate consolidation. Taken together, the consolidation of α'β' MB neuron fate requires the response of progenitors to local signalling to enable postmitotic neurons to sense a systemic signal.
- Published
- 2019
- Full Text
- View/download PDF
5. Structural aspects of plasticity in the nervous system of Drosophila
- Author
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Atsushi Sugie, Giovanni Marchetti, and Gaia Tavosanis
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Structural plasticity ,Drosophila ,Photoreceptors ,Synapse ,Active zone ,Mushroom body ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Neurons extend and retract dynamically their neurites during development to form complex morphologies and to reach out to their appropriate synaptic partners. Their capacity to undergo structural rearrangements is in part maintained during adult life when it supports the animal’s ability to adapt to a changing environment or to form lasting memories. Nonetheless, the signals triggering structural plasticity and the mechanisms that support it are not yet fully understood at the molecular level. Here, we focus on the nervous system of the fruit fly to ask to which extent activity modulates neuronal morphology and connectivity during development. Further, we summarize the evidence indicating that the adult nervous system of flies retains some capacity for structural plasticity at the synaptic or circuit level. For simplicity, we selected examples mostly derived from studies on the visual system and on the mushroom body, two regions of the fly brain with extensively studied neuroanatomy.
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- 2018
- Full Text
- View/download PDF
6. Cell-Autonomous Control of Neuronal Dendrite Expansion via the Fatty Acid Synthesis Regulator SREBP
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Anna B. Ziegler, Christoph Thiele, Federico Tenedini, Mélisande Richard, Philipp Leyendecker, Astrid Hoermann, Peter Soba, and Gaia Tavosanis
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Biology (General) ,QH301-705.5 - Abstract
Summary: During differentiation, neurons require a high lipid supply for membrane formation as they elaborate complex dendritic morphologies. While glia-derived lipids support neuronal growth during development, the importance of cell-autonomous lipid production for dendrite formation has been unclear. Using Drosophila larva dendritic arborization (da) neurons, we show that dendrite expansion relies on cell-autonomous fatty acid production. The nociceptive class four (CIV) da neurons form particularly large space-filling dendrites. We show that dendrite formation in these CIVda neurons additionally requires functional sterol regulatory element binding protein (SREBP), a crucial regulator of fatty acid production. The dendrite simplification in srebp mutant CIVda neurons is accompanied by hypersensitivity of srebp mutant larvae to noxious stimuli. Taken together, our work reveals that cell-autonomous fatty acid production is required for proper dendritic development and establishes the role of SREBP in complex neurons for dendrite elaboration and function. : Ziegler et al. highlight the endogenous role of fatty acid synthesis for proper neuronal dendrite growth during development. Using Drosophila da neurons, they show that large CIVda neurons cell-autonomously rely on fatty acid synthesis through the lipid synthesis master regulator SREBP. Keywords: Drosophila, dendrite differentiation, fatty acids, lipids, SREBP, metabolism, brain, nociception
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- 2017
- Full Text
- View/download PDF
7. Drosophila Dendritic Arborisation Neurons: Fantastic Actin Dynamics and Where to Find Them
- Author
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Lukas Kilo, Tomke Stürner, Gaia Tavosanis, and Anna B. Ziegler
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neuronal dendrites ,dendrite arborization (da) neurons ,actin ,time-lapse imaging ,Cytology ,QH573-671 - Abstract
Neuronal dendrites receive, integrate, and process numerous inputs and therefore serve as the neuron’s “antennae”. Dendrites display extreme morphological diversity across different neuronal classes to match the neuron’s specific functional requirements. Understanding how this structural diversity is specified is therefore important for shedding light on information processing in the healthy and diseased nervous system. Popular models for in vivo studies of dendrite differentiation are the four classes of dendritic arborization (c1da–c4da) neurons of Drosophila larvae with their class-specific dendritic morphologies. Using da neurons, a combination of live-cell imaging and computational approaches have delivered information on the distinct phases and the time course of dendrite development from embryonic stages to the fully developed dendritic tree. With these data, we can start approaching the basic logic behind differential dendrite development. A major role in the definition of neuron-type specific morphologies is played by dynamic actin-rich processes and the regulation of their properties. This review presents the differences in the growth programs leading to morphologically different dendritic trees, with a focus on the key role of actin modulatory proteins. In addition, we summarize requirements and technological progress towards the visualization and manipulation of such actin regulators in vivo.
- Published
- 2021
- Full Text
- View/download PDF
8. Assessing the role of cell-surface molecules in central synaptogenesis in the Drosophila visual system.
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Sandra Berger-Müller, Atsushi Sugie, Fumio Takahashi, Gaia Tavosanis, Satoko Hakeda-Suzuki, and Takashi Suzuki
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Medicine ,Science - Abstract
A hallmark of the central nervous system is its spatial and functional organization in synaptic layers. During neuronal development, axons form transient contacts with potential post-synaptic elements and establish synapses with appropriate partners at specific layers. These processes are regulated by synaptic cell-adhesion molecules. In the Drosophila visual system, R7 and R8 photoreceptor subtypes target distinct layers and form en passant pre-synaptic terminals at stereotypic loci of the axonal shaft. A leucine-rich repeat transmembrane protein, Capricious (Caps), is known to be selectively expressed in R8 axons and their recipient layer, which led to the attractive hypothesis that Caps mediates R8 synaptic specificity by homophilic adhesion. Contradicting this assumption, our results indicate that Caps does not have a prominent role in synaptic-layer targeting and synapse formation in Drosophila photoreceptors, and that the specific recognition of the R8 target layer does not involve Caps homophilic axon-target interactions. We generated flies that express a tagged synaptic marker to evaluate the presence and localization of synapses in R7 and R8 photoreceptors. These genetic tools were used to assess how the synaptic profile is affected when axons are forced to target abnormal layers by expressing axon guidance molecules. When R7 axons were mistargeted to the R8-recipient layer, R7s either maintained an R7-like synaptic profile or acquired a similar profile to r8s depending on the overexpressed protein. When R7 axons were redirected to a more superficial medulla layer, the number of presynaptic terminals was reduced. These results indicate that cell-surface molecules are able to dictate synapse loci by changing the axon terminal identity in a partially cell-autonomous manner, but that presynapse formation at specific sites also requires complex interactions between pre- and post-synaptic elements.
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- 2013
- Full Text
- View/download PDF
9. A Quantitative Model of Sporadic Axonal Degeneration in the Drosophila Visual System
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Hiroki Kawai, Gaia Tavosanis, Mélisande Richard, Karolína Doubková, Yohei Nitta, and Atsushi Sugie
- Subjects
physiology [Axons] ,General Neuroscience ,Stimulation ,Neurodegenerative Diseases ,Degeneration (medical) ,Biology ,Neurotransmission ,Quantitative model ,Stereotypy (non-human) ,nervous system ,genetics [Drosophila Proteins] ,Postsynaptic potential ,Animals ,Female ,ddc:610 ,physiology [Synapses] ,Neuroscience ,Constant light ,Axonal degeneration ,physiology [Drosophila] - Abstract
In human neurodegenerative diseases, neurons undergo axonal degeneration months to years before they die. Here, we developed a system modelling early degenerative events in Drosophila adult photoreceptor cells. Thanks to the stereotypy of their axonal projections, this system delivers quantitative data on sporadic and progressive axonal degeneration of photoreceptor cells. Using this method, we show that exposure of adult female flies to a constant light stimulation for several days overcomes the intrinsic resilience of R7 photoreceptors and leads to progressive axonal degeneration. This was not associated with apoptosis. We furthermore provide evidence that loss of synaptic integrity between R7 and a postsynaptic partner preceded axonal degeneration, thus recapitulating features of human neurodegenerative diseases. Finally, our experiments uncovered a role of postsynaptic partners of R7 to initiate degeneration, suggesting that postsynaptic cells signal back to the photoreceptor to maintain axonal structure. This model can be used to dissect cellular and circuit mechanisms involved in the early events of axonal degeneration, allowing for a better understanding of how neurons cope with stress and lose their resilience capacities.SIGNIFICANCE STATEMENT:Neurons can be active and functional for several years. In the course of ageing and in disease conditions leading to neurodegeneration, subsets of neurons lose their resilience and start dying. What initiates this turning point at the cellular level is not clear. Here, we developed a model allowing to systematically describe this phase. The loss of synapses and axons represents an early and functionally relevant event towards degeneration. Utilizing the ordered distribution of Drosophila photoreceptors axon terminals, we assembled a system to study sporadic initiation of axon loss and delineated a role for non-cell-autonomous activity regulation in the initiation of axon degeneration. This work will help shedding light on key steps in the etiology of non-familial cases of neurodegenerative diseases.
- Published
- 2022
10. Direct evaluation of neuroaxonal degeneration with the causative genes of neurodegenerative diseases in drosophila using the automated axon quantification system, MeDUsA
- Author
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Yohei Nitta, Hiroki Kawai, Ryuto Maki, Jiro Osaka, Satoko Hakeda-Suzuki, Yoshitaka Nagai, Karolína Doubková, Tomoko Uehara, Kenji Watanabe, Kenjiro Kosaki, Takashi Suzuki, Gaia Tavosanis, and Atsushi Sugie
- Subjects
ddc:570 ,Genetics ,General Medicine ,Molecular Biology ,Genetics (clinical) - Abstract
Drosophila is an excellent model organism for studying human neurodegenerative diseases (NDs). However, there is still almost no experimental system that could directly observe the degeneration of neurons and automatically quantify axonal degeneration. In this study, we created MeDUsA (a ‘method for the quantification of degeneration using fly axons’), a standalone executable computer program based on Python that combines a pre-trained deep-learning masking tool with an axon terminal counting tool. This software automatically quantifies the number of retinal R7 axons in Drosophila from a confocal z-stack image series. Using this software, we were able to directly demonstrate that axons were degenerated by the representative causative genes of NDs for the first time in Drosophila. The fly retinal axon is an excellent experimental system that is capable of mimicking the pathology of axonal degeneration in human NDs. MeDUsA rapidly and accurately quantifies axons in Drosophila photoreceptor neurons. It enables large-scale research into axonal degeneration, including screening to identify genes or drugs that mediate axonal toxicity caused by ND proteins and diagnose the pathological significance of novel variants of human genes in axons.
- Published
- 2022
11. The branching code: A model of actin-driven dendrite arborization
- Author
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Tomke Stürner, André Ferreira Castro, Maren Philipps, Hermann Cuntz, and Gaia Tavosanis
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computational modeling ,Molecular biology [CP] ,Neuronal Plasticity ,metabolism [Actins] ,morphometrics ,Neuroscience [CP] ,metabolism [Drosophila Proteins] ,time-lapse imaging ,Dendrites ,optimal wiring ,metabolism [Drosophila] ,General Biochemistry, Genetics and Molecular Biology ,neuron ,Actins ,dendrite ,dendritic arborization neurons ,Animals ,Drosophila Proteins ,metabolism [Dendrites] ,Drosophila ,ddc:610 ,actin-modulatory proteins ,actin - Abstract
Summary The cytoskeleton is crucial for defining neuronal-type-specific dendrite morphologies. To explore how the complex interplay of actin-modulatory proteins (AMPs) can define neuronal types in vivo, we focused on the class III dendritic arborization (c3da) neuron of Drosophila larvae. Using computational modeling, we reveal that the main branches (MBs) of c3da neurons follow general models based on optimal wiring principles, while the actin-enriched short terminal branches (STBs) require an additional growth program. To clarify the cellular mechanisms that define this second step, we thus concentrated on STBs for an in-depth quantitative description of dendrite morphology and dynamics. Applying these methods systematically to mutants of six known and novel AMPs, we revealed the complementary roles of these individual AMPs in defining STB properties. Our data suggest that diverse dendrite arbors result from a combination of optimal-wiring-related growth and individualized growth programs that are neuron-type specific.
- Published
- 2022
12. Author response: The anterior paired lateral neuron normalizes odour-evoked activity in the Drosophila mushroom body calyx
- Author
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Luigi Prisco, Stephan Hubertus Deimel, Hanna Yeliseyeva, André Fiala, and Gaia Tavosanis
- Published
- 2021
13. MeDUsA: A novel system for automated axon quantification to evaluate neuroaxonal degeneration
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Takashi Suzuki, Satoko Hakeda-Suzuki, Hiroki Kawai, Gaia Tavosanis, Jiro Osaka, Atsushi Sugie, Yoshitaka Nagai, Yohei Nitta, and Karolína Doubková
- Subjects
Human disease ,medicine.anatomical_structure ,Axon terminal ,ved/biology ,ved/biology.organism_classification_rank.species ,medicine ,Degeneration (medical) ,Biology ,Axon ,Model organism ,Axonal degeneration ,Neuroscience ,Phenotype - Abstract
BackgroundDrosophila is an excellent model organism for studying human neurodegenerative diseases (NDs), and the rough eye phenotype (REP) assay is a convenient experimental system for analysing the toxicity of ectopically expressed human disease genes. However, the association between REP and axonal degeneration, an early sign of ND, remains unclear. To address this question, we developed a method to evaluate axonal degeneration by quantifying the number of retinal R7 axons in Drosophila; however, it requires expertise and is time-consuming. Therefore, there is a need for an easy-to-use software that can automatically quantify the axonal degeneration.ResultWe created MeDUsA (a ‘method for the quantification of degeneration using fly axons’), which is a standalone executable computer program based on Python that combines a pre-trained deep-learning masking tool with an axon terminal counting tool. This software automatically quantifies the number of axons from a confocal z-stack image series. Using this software, we have demonstrated for the first time directly that axons degenerate when the causative factors of NDs (αSyn, Tau, TDP-43, HTT) were expressed in the Drosophila eye. Furthermore, we compared axonal toxicity of the representative causative genes of NDs and their pathological alleles with REP and found no significant correlation between them.ConclusionsMeDUsA rapidly and accurately quantifies axons in Drosophila eye. By simplifying and automating time-consuming manual efforts requiring significant expertise, it enables large-scale, complex research efforts on axonal degeneration, such as screening to identify genes or drugs that mediate axonal toxicity caused by ND disease proteins.
- Published
- 2021
14. A Quantitative Model of Sporadic Axonal Degeneration in the
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Mélisande, Richard, Karolína, Doubková, Yohei, Nitta, Hiroki, Kawai, Atsushi, Sugie, and Gaia, Tavosanis
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Synapses ,Animals ,Drosophila Proteins ,Drosophila ,Female ,Neurodegenerative Diseases ,Axons - Abstract
In human neurodegenerative diseases, neurons undergo axonal degeneration months to years before they die. Here, we developed a system modeling early degenerative events in
- Published
- 2021
15. The anterior paired lateral neuron normalizes odour-evoked activity at the mushroom body calyx
- Author
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Hanna Yeliseyeva, Gaia Tavosanis, André Fiala, Luigi Prisco, and Stephan Hubertus Deimel
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0303 health sciences ,Sensory system ,Biology ,Content-addressable memory ,Inhibitory postsynaptic potential ,Calyx ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Calcium imaging ,Postsynaptic potential ,Mushroom bodies ,medicine ,Neuron ,Neuroscience ,030217 neurology & neurosurgery ,030304 developmental biology - Abstract
To identify and memorize discrete but similar environmental inputs, the brain needs to distinguish between subtle differences of activity patterns in defined neuronal populations. The Kenyon cells of the Drosophila adult mushroom body (MB) respond sparsely to complex olfactory input, a property that is thought to support stimuli discrimination in the MB. To understand how this property emerges, we investigated the role of the inhibitory anterior paired lateral neuron (APL) in the input circuit of the MB, the calyx. Within the calyx, presynaptic boutons of projection neurons (PNs) form large synaptic microglomeruli (MGs) with dendrites of postsynaptic Kenyon cells (KCs). Combining EM data analysis and in vivo calcium imaging, we show that APL, via inhibitory and reciprocal synapses targeting both PN boutons and KC dendrites, normalizes odour-evoked representations in MGs of the calyx. APL response scales with the PN input strength and is regionalized around PN input distribution. Our data indicate that the formation of a sparse code by the Kenyon cells requires APL-driven normalization of their MG postsynaptic responses. This work provides experimental insights on how inhibition shapes sensory information representation in a higher brain centre, thereby supporting stimuli discrimination and allowing for efficient associative memory formation.
- Published
- 2021
16. Dendrite enlightenment
- Author
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Gaia Tavosanis
- Subjects
Neurons ,General Neuroscience ,Animals ,ddc:610 ,Dendrites - Abstract
Neuronal dendrites acquire complex morphologies during development. These are not just the product of cell-intrinsic developmental programs; rather they are defined in close interaction with the cellular environment. Thus, to understand the molecular cascades that yield appropriate morphologies, it is essential to investigate them in vivo, in the actual complex tissue environment encountered by the differentiating neuron in the developing animal. Particularly, genetic approaches have pointed to factors controlling dendrite differentiation in vivo. These suggest that localized and transient molecular cascades might underlie the formation and stabilization of dendrite branches with neuron type-specific characteristics. Here, I highlight the need for studies of neuronal dendrite differentiation in the animal, the challenges provided by such an approach, and the promising pathways that have recently opened.
- Published
- 2021
17. Circuit reorganization in the Drosophila mushroom body calyx accompanies memory consolidation
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Philipp Ranft, Gaia Tavosanis, J. Scott Lauritzen, Lothar Baltruschat, André Fiala, Davi D. Bock, and Luigi Prisco
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0301 basic medicine ,Kenyon cell ,drug effects [Memory Consolidation] ,drug effects [Synapses] ,Oleic Acids ,Pheromones ,0302 clinical medicine ,drug effects [Neuronal Plasticity] ,drug effects [Axons] ,functional imaging ,functional plasticity ,Neuronal Plasticity ,Consolidation (soil) ,drug effects [Memory, Long-Term] ,physiology [Memory Consolidation] ,structural plasticity ,pharmacology [Oleic Acids] ,microglomerulus ,memory consolidation ,Drosophila melanogaster ,innervation [Mushroom Bodies] ,Mushroom bodies ,Memory consolidation ,physiology [Nerve Net] ,Drosophila ,projection neuron ,Olfactory Learning ,Memory, Long-Term ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Article ,Calyx ,mushroom body calyx ,03 medical and health sciences ,ultrastructure [Nerve Net] ,drug effects [Nerve Net] ,ultrastructure [Drosophila melanogaster] ,Animals ,ddc:610 ,Mushroom Bodies ,Memory Consolidation ,physiology [Axons] ,drug effects [Mushroom Bodies] ,mushroom body ,physiology [Drosophila melanogaster] ,Axons ,030104 developmental biology ,Odor ,pharmacology [Pheromones] ,Synaptic plasticity ,ultrastructure [Synapses] ,Odorants ,Synapses ,ultrastructure [Mushroom Bodies] ,physiology [Synapses] ,Nerve Net ,drug effects [Drosophila melanogaster] ,Neuroscience ,030217 neurology & neurosurgery - Abstract
The formation and consolidation of memories are complex phenomena involving synaptic plasticity, microcircuit reorganization, and the formation of multiple representations within distinct circuits. To gain insight into the structural aspects of memory consolidation, we focus on the calyx of the Drosophila mushroom body. In this essential center, essential for olfactory learning, second- and third-order neurons connect through large synaptic microglomeruli, which we dissect at the electron microscopy level. Focusing on microglomeruli that respond to a specific odor, we reveal that appetitive long-term memory results in increased numbers of precisely those functional microglomeruli responding to the conditioned odor. Hindering memory consolidation by non-coincident presentation of odor and reward, by blocking protein synthesis, or by including memory mutants suppress these structural changes, revealing their tight correlation with the process of memory consolidation. Thus, olfactory long-term memory is associated with input-specific structural modifications in a high-order center of the fly brain.
- Published
- 2021
18. Drosophila Dendritic Arborisation Neurons: Fantastic Actin Dynamics and Where to Find Them
- Author
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Anna B. Ziegler, Lukas Kilo, Gaia Tavosanis, Tomke Stürner, Kilo, Lukas [0000-0002-2787-044X], Stürner, Tomke [0000-0003-4054-0784], Tavosanis, Gaia [0000-0002-8679-5515], and Apollo - University of Cambridge Repository
- Subjects
Nervous system ,metabolism [Actins] ,QH301-705.5 ,Dendrite ,time-lapse imaging ,Review ,Biology ,metabolism [Drosophila] ,ddc:570 ,Actin dynamics ,dendrite arborization (da) neurons ,medicine ,Animals ,metabolism [Dendrites] ,Biology (General) ,Process (anatomy) ,Actin ,neuronal dendrites ,Cell Differentiation ,General Medicine ,Dendrites ,Embryonic stem cell ,Actins ,medicine.anatomical_structure ,Time course ,Drosophila ,Neuron ,Neuroscience ,actin - Abstract
Neuronal dendrites receive, integrate, and process numerous inputs and therefore serve as the neuron’s “antennae”. Dendrites display extreme morphological diversity across different neuronal classes to match the neuron’s specific functional requirements. Understanding how this structural diversity is specified is therefore important for shedding light on information processing in the healthy and diseased nervous system. Popular models for in vivo studies of dendrite differentiation are the four classes of dendritic arborization (c1da–c4da) neurons of Drosophila larvae with their class-specific dendritic morphologies. Using da neurons, a combination of live-cell imaging and computational approaches have delivered information on the distinct phases and the time course of dendrite development from embryonic stages to the fully developed dendritic tree. With these data, we can start approaching the basic logic behind differential dendrite development. A major role in the definition of neuron-type specific morphologies is played by dynamic actin-rich processes and the regulation of their properties. This review presents the differences in the growth programs leading to morphologically different dendritic trees, with a focus on the key role of actin modulatory proteins. In addition, we summarize requirements and technological progress towards the visualization and manipulation of such actin regulators in vivo.
- Published
- 2021
19. Achieving functional neuronal dendrite structure through sequential stochastic growth and retraction
- Author
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Gaia Tavosanis, Amirhoushang Bahrami, Tomke Stürner, Lothar Baltruschat, Peter Jedlicka, Hermann Cuntz, André Ferreira Castro, Ferreira Castro, André [0000-0002-6841-1952], Stürner, Tomke [0000-0003-4054-0784], Bahrami, Amirhoushang [0000-0001-5841-2516], Jedlicka, Peter [0000-0001-6571-5742], Tavosanis, Gaia [0000-0002-8679-5515], Cuntz, Hermann [0000-0001-5445-0507], and Apollo - University of Cambridge Repository
- Subjects
dendrite retraction ,Sensory Receptor Cells ,QH301-705.5 ,Science ,self-organisation ,Green Fluorescent Proteins ,Morphogenesis ,metabolism [Drosophila Proteins] ,Sensory system ,Crawling ,Dendritic branch ,Biology ,General Biochemistry, Genetics and Molecular Biology ,neuroscience ,Animals, Genetically Modified ,developmental biology ,Dendrite (crystal) ,dendrite growth ,physiology [Gene Expression Regulation, Developmental] ,genetics [Green Fluorescent Proteins] ,Animals ,Drosophila Proteins ,Biology (General) ,Mechanotransduction ,mechanotransduction ,D. melanogaster ,General Immunology and Microbiology ,General Neuroscience ,fungi ,Gene Expression Regulation, Developmental ,physiology [Dendrites] ,Dendrites ,General Medicine ,physiology [Morphogenesis] ,Membrane curvature ,Medicine ,Drosophila ,computer model ,physiology [Sensory Receptor Cells] ,ddc:600 ,physiology [Drosophila] ,Neuroscience ,Developmental biology ,dendrite function ,Research Article - Abstract
Class I ventral posterior dendritic arborisation (c1vpda) proprioceptive sensory neurons respond to contractions in theDrosophilalarval body wall during crawling. Their dendritic branches run along the direction of contraction, possibly a functional requirement to maximise membrane curvature during crawling contractions. Although the molecular machinery of dendritic patterning in c1vpda has been extensively studied, the process leading to the precise elaboration of their comb-like shapes remains elusive. Here, to link dendrite shape with its proprioceptive role, we performed long-term, non-invasive,in vivotime-lapse imaging of c1vpda embryonic and larval morphogenesis to reveal a sequence of differentiation stages. We combined computer models and dendritic branch dynamics tracking to propose that distinct sequential phases of targeted growth and stochastic retraction achieve efficient dendritic trees both in terms of wire and function. Our study shows how dendrite growth balances structure–function requirements, shedding new light on general principles of self-organisation in functionally specialised dendrites.In briefAn optimal wire and function trade-off emerges from noisy growth and stochastic retraction duringDrosophilaclass I ventral posterior dendritic arborisation (c1vpda) dendrite development.HighlightsC1vpda dendrite outgrowth follows wire constraints.Stochastic retraction of functionally suboptimal branches in a subsequent growth phase.C1vpda growth rules favour branches running parallel to larval body wall contraction.Comprehensive growth model reproduces c1vpda developmentin silico.
- Published
- 2020
20. Author response: Achieving functional neuronal dendrite structure through sequential stochastic growth and retraction
- Author
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André Ferreira Castro, Hermann Cuntz, Lothar Baltruschat, Tomke Stürner, Peter Jedlicka, Gaia Tavosanis, and Amirhoushang Bahrami
- Subjects
Materials science ,Dendrite (mathematics) ,Biophysics - Published
- 2020
21. The branching code: a model of actin-driven dendrite arborisation
- Author
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Tomke Stürner, Gaia Tavosanis, Hermann Cuntz, Maren Philipps, and André Ferreira Castro
- Subjects
Characteristic morphology ,medicine.anatomical_structure ,medicine ,Neuronal cytoskeleton ,Dendrite ,Neuron ,Growth model ,Biology ,Branching (polymer chemistry) ,Neuroscience ,Actin ,Drosophila larvae - Abstract
SummaryDendrites display a striking variety of neuronal type-specific morphologies, but the mechanisms and principles underlying such diversity remain elusive. A major player in defining the morphology of dendrites is the neuronal cytoskeleton, including evolutionarily conserved actin-modulatory proteins (AMPs). Still, we lack a clear understanding of how AMPs might support developmental phenomena such as neuron-type specific dendrite dynamics. To address precisely this level ofin vivospecificity, we concentrated on a defined neuronal type, the class III dendritic arborisation (c3da) neuron ofDrosophilalarvae, displaying actin-enriched short terminal branchlets (STBs). Computational modelling reveals that the main branches of c3da neurons follow a general growth model based on optimal wiring, but the STBs do not. Instead, model STBs are defined by a short reach and a high affinity to grow towards the main branches. We thus concentrated on c3da STBs and developed new methods to quantitatively describe dendrite morphology and dynamics based onin vivotime-lapse imaging of mutants lacking individual AMPs. In this way, we extrapolated the role of these AMPs in defining STB properties. We propose that dendrite diversity is supported by the combination of a common step, refined by a neuron type-specific second level. For c3da neurons, we present a molecular model of how the combined action of multiple AMPsin vivodefine the properties of these second level specialisations, the STBs.In briefA quantitative morphological dissection of the concerted actin-modulatory protein actions provides a model of dendrite branchlet outgrowth.HighlightsActin organisation in small terminal branchlets ofDrosophilaclass III dendritic arborisation neuronsSix actin-modulatory proteins individually control the characteristic morphology and dynamics of branchletsQuantitative tools for dendrite morphology and branch dynamics enable a comparative analysisA two-step computational growth model reproduces c3da dendrite morphology
- Published
- 2020
22. Circuit reorganization in the Drosophila mushroom body calyx accompanies memory consolidation
- Author
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Lothar Baltruschat, J. Scott Lauritzen, Davi D. Bock, Andr eacute Fiala, Luigi Prisco, Philipp Ranft, and Gaia Tavosanis
- Subjects
Nervous system ,0303 health sciences ,Computer science ,Classical conditioning ,Engram ,Content-addressable memory ,Synapse ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Postsynaptic potential ,Mushroom bodies ,medicine ,Memory consolidation ,Neuroscience ,030217 neurology & neurosurgery ,030304 developmental biology - Abstract
SummaryThe capacity of utilizing past experience to guide future action is a fundamental and conserved function of the nervous system. Associative memory formation initiated by the coincident detection of a conditioned stimulus (CS, e.g. odour) and an unconditioned stimulus (US, e.g. sugar reward) can lead to a short-lived memory trace (STM) within distinct circuits [1-5]. Memories can be consolidated into long-term memories (LTM) through processes that are not fully understood, but depend on de-novo protein synthesis [6, 7], require structural modifications within the involved neuronal circuits and might lead to the recruitment of additional ones [8-17]. Compared to modulation of existing connections, the reorganization of circuits affords the unique possibility of sampling for potential new partners [18-20]. Nonetheless, only few examples of rewiring associated with learning have been established thus far [14, 21-24]. Here, we report that memory consolidation is associated with the structural and functional reorganization of an identified circuit in the adult fly brain. The formation and retrieval of olfactory associative memories in Drosophila requires the mushroom body (MB) [25]. We identified the individual synapses of olfactory projection neurons (PNs) that deliver a conditioned odour to the MB and reconstructed the complexity of the microcircuit they form. Combining behavioural experiments with high-resolution microscopy and functional imaging, we demonstrated that the consolidation of appetitive olfactory memories closely correlates with an increase in the number of synaptic complexes formed by the PNs that deliver the conditioned stimulus and their postsynaptic partners. These structural changes result in additional functional synaptic connections.
- Published
- 2020
23. A developmental stretch-and-fill process that optimises dendritic wiring
- Author
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Hermann Cuntz, Gaia Tavosanis, and Lothar Baltruschat
- Subjects
Dendrite (crystal) ,medicine.anatomical_structure ,Basis (linear algebra) ,Computer science ,Process (computing) ,medicine ,Dendrite ,Space (mathematics) ,Topology - Abstract
The way in which dendrites spread within neural tissue determines the resulting circuit connectivity and computation. However, a general theory describing the dynamics of this growth process does not exist. Here we obtain the first time-lapse reconstructions of neurons in living fly larvae over the entirety of their developmental stages. We show that these neurons expand in a remarkably regular stretching process that conserves their shape. Newly available space is filled optimally, a direct consequence of constraining the total amount of dendritic cable. We derive a mathematical model that predicts one time point from the previous and use this model to predict dendrite morphology of other cell types and species. In summary, we formulate a novel theory of dendrite growth based on detailed developmental experimental data that optimises wiring and space filling and serves as a basis to better understand aspects of coverage and connectivity for neural circuit formation.In briefWe derive a detailed mathematical model that describes long-term time-lapse data of growing dendrites; it optimises total wiring and space-filling.HighlightsDendrite growth iterations guarantee optimal wiring at each iteration.Optimal wiring guarantees optimal space filling.The growth rule from fly predicts dendrites of other cell types and species.Fly neurons stretch-and-fill target area with precise scaling relations.Phase transition of growth process between fly embryo and larval stages.
- Published
- 2020
24. Glycerophospholipids - Emerging players in neuronal dendrite branching and outgrowth
- Author
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Anna B. Ziegler and Gaia Tavosanis
- Subjects
Dendritic spine ,metabolism [Glycerophospholipids] ,Dendritic Spines ,Neuronal differentiation ,Glycerophospholipids ,Biology ,03 medical and health sciences ,Dendrite (crystal) ,0302 clinical medicine ,ddc:570 ,medicine ,Compartment (development) ,Animals ,Humans ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,Cell Differentiation ,Cell Biology ,physiology [Cell Differentiation] ,medicine.anatomical_structure ,metabolism [Dendritic Spines] ,Neuron ,Neuroscience ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
Dendrites are the input compartment of the neuron, receiving and integrating incoming information. Dendritic trees are often highly complex and branched. Their branch extension and distribution are tightly correlated with their role and interactions within neuronal networks. Thus, intense research has focused on understanding the mechanisms that govern dendrite elaboration. Recent reports highlight the importance of specific lipids for these processes. In particular, glycerophospholipids and several of their interacting proteins are involved in various steps of dendrite growth, including the initiation and elongation of dendritic branches and dendritic spines. The aim of this review is to provide a general overview about which particular lipids are involved in shaping dendrite morphology during neuronal differentiation. Additionally, it summarizes recent studies, which helped to gain insights into the mechanisms by which glycerophospholipids and their associated proteins contribute to establishing correct dendritic morphologies.
- Published
- 2018
25. Transient localization of the Arp2/3 complex initiates neuronal dendrite branching
- Author
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Gaia Tavosanis, Tomke Stürner, Maria Nemethova, Sven Bogdan, Vic Small, Jan Mueller, Yun Zhang, Anastasia Tatarnikova, Barbara Schaffran, and Hermann Cuntz
- Subjects
Nervous system ,metabolism [Actins] ,Sensory Receptor Cells ,metabolism [Actin-Related Protein 2-3 Complex] ,Synaptogenesis ,Morphogenesis ,Arp2/3 complex ,macromolecular substances ,Biology ,Actin-Related Protein 2-3 Complex ,03 medical and health sciences ,0302 clinical medicine ,ddc:570 ,medicine ,metabolism [Sensory Receptor Cells] ,Animals ,metabolism [Dendrites] ,Small GTPase ,metabolism [Actin Cytoskeleton] ,Molecular Biology ,genetics [Actin-Related Protein 2-3 Complex] ,Actin ,030304 developmental biology ,0303 health sciences ,Dendrites ,Actins ,Actin Cytoskeleton ,medicine.anatomical_structure ,Drosophila melanogaster ,Receptive field ,biology.protein ,Biophysics ,Drosophila ,Neuron ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
The formation of neuronal dendrite branches is fundamental for the wiring and function of the nervous system. Indeed, dendrite branching enhances the coverage of the neuron's receptive field and modulates the initial processing of incoming stimuli. Complex dendrite patterns are achieved in vivo through a dynamic process of de novo branch formation, branch extension and retraction. The first step towards branch formation is the generation of a dynamic filopodium-like branchlet. The mechanisms underlying the initiation of dendrite branchlets are therefore crucial to the shaping of dendrites. Through in vivo time-lapse imaging of the subcellular localization of actin during the process of branching of Drosophila larva sensory neuron combined with genetic analysis and electron tomography we identified the (Actin related protein) Arp2/3 complex as the major actin-nucleator involved in the initiation of dendrite branchlet formation, under the control of the activator WAVE and of the small GTPase Rac1. Transient recruitment of an Arp2/3 component marks in vivo the site of branchlet initiation. These data position the activation of Arp2/3 as an early hub for the initiation of branchlet formation.
- Published
- 2018
26. Structural aspects of plasticity in the nervous system of Drosophila
- Author
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Giovanni Marchetti, Atsushi Sugie, and Gaia Tavosanis
- Subjects
Photoreceptors ,0301 basic medicine ,Nervous system ,Developmental cognitive neuroscience ,Review ,Nervous System ,lcsh:RC346-429 ,Synapse ,03 medical and health sciences ,Developmental Neuroscience ,ddc:570 ,medicine ,physiology [Neuronal Plasticity] ,Animals ,Learning ,Active zone ,Drosophila ,lcsh:Neurology. Diseases of the nervous system ,Structural plasticity ,Neuronal Plasticity ,biology ,fungi ,Mushroom body ,biology.organism_classification ,030104 developmental biology ,medicine.anatomical_structure ,Synapses ,Mushroom bodies ,physiology [Synapses] ,cytology [Nervous System] ,Mushroom body calyx ,physiology [Drosophila] ,Neuroscience ,Developmental biology ,Neuroanatomy - Abstract
Neurons extend and retract dynamically their neurites during development to form complex morphologies and to reach out to their appropriate synaptic partners. Their capacity to undergo structural rearrangements is in part maintained during adult life when it supports the animal’s ability to adapt to a changing environment or to form lasting memories. Nonetheless, the signals triggering structural plasticity and the mechanisms that support it are not yet fully understood at the molecular level. Here, we focus on the nervous system of the fruit fly to ask to which extent activity modulates neuronal morphology and connectivity during development. Further, we summarize the evidence indicating that the adult nervous system of flies retains some capacity for structural plasticity at the synaptic or circuit level. For simplicity, we selected examples mostly derived from studies on the visual system and on the mushroom body, two regions of the fly brain with extensively studied neuroanatomy.
- Published
- 2018
27. Analyzing Synaptic Modulation of Drosophila melanogaster Photoreceptors after Exposure to Prolonged Light
- Author
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Atsushi Sugie, Takashi Suzuki, Gaia Tavosanis, Christoph Möhl, Satoko Hakeda-Suzuki, and Hideaki Matsui
- Subjects
0301 basic medicine ,Nervous system ,General Immunology and Microbiology ,General Chemical Engineering ,General Neuroscience ,Biology ,Neurotransmission ,General Biochemistry, Genetics and Molecular Biology ,Cell biology ,Synapse ,03 medical and health sciences ,030104 developmental biology ,medicine.anatomical_structure ,Axon terminal ,medicine ,Neuron ,Active zone ,Axon ,Neuroscience ,Drosophila Protein - Abstract
The nervous system has the remarkable ability to adapt and respond to various stimuli. This neural adjustment is largely achieved through plasticity at the synaptic level. The Active Zone (AZ) is the region at the presynaptic membrane that mediates neurotransmitter release and is composed of a dense collection of scaffold proteins. AZs of Drosophila melanogaster (Drosophila) photoreceptors undergo molecular remodeling after prolonged exposure to natural ambient light. Thus the level of neuronal activity can rearrange the molecular composition of the AZ and contribute to the regulation of the functional output. Starting from the light exposure set-up preparation to the immunohistochemistry, this protocol details how to quantify the number, the spatial distribution, and the delocalization level of synaptic molecules at AZs in Drosophila photoreceptors. Using image analysis software, clusters of the GFP-fused AZ component Bruchpilot were identified for each R8 photoreceptor (R8) axon terminal. Detected Bruchpilot spots were automatically assigned to individual R8 axons. To calculate the distribution of spot frequency along the axon, we implemented a customized software plugin. Each axon's start-point and end-point were manually defined and the position of each Bruchpilot spot was projected onto the connecting line between start and end-point. Besides the number of Bruchpilot clusters, we also quantified the delocalization level of Bruchpilot-GFP within the clusters. These measurements reflect in detail the spatially resolved synaptic dynamics in a single neuron under different environmental conditions to stimuli.
- Published
- 2017
28. Analyzing Synaptic Modulation of Drosophila melanogaster Photoreceptors after Exposure to Prolonged Light
- Author
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Atsushi, Sugie, Christoph, Möhl, Satoko, Hakeda-Suzuki, Hideaki, Matsui, Takashi, Suzuki, and Gaia, Tavosanis
- Subjects
Luminescent Agents ,Light ,metabolism [Luminescent Agents] ,Green Fluorescent Proteins ,Presynaptic Terminals ,metabolism [Drosophila Proteins] ,metabolism [Synapses] ,Synaptic Transmission ,metabolism [Photoreceptor Cells, Invertebrate] ,Protein Transport ,Drosophila melanogaster ,physiology [Synaptic Transmission] ,ddc:570 ,metabolism [Green Fluorescent Proteins] ,Synapses ,metabolism [Drosophila melanogaster] ,Animals ,radiation effects [Photoreceptor Cells, Invertebrate] ,Drosophila Proteins ,Photoreceptor Cells, Invertebrate ,Neuroscience ,Protein Binding - Abstract
The nervous system has the remarkable ability to adapt and respond to various stimuli. This neural adjustment is largely achieved through plasticity at the synaptic level. The Active Zone (AZ) is the region at the presynaptic membrane that mediates neurotransmitter release and is composed of a dense collection of scaffold proteins. AZs of Drosophila melanogaster (Drosophila) photoreceptors undergo molecular remodeling after prolonged exposure to natural ambient light. Thus the level of neuronal activity can rearrange the molecular composition of the AZ and contribute to the regulation of the functional output. Starting from the light exposure set-up preparation to the immunohistochemistry, this protocol details how to quantify the number, the spatial distribution, and the delocalization level of synaptic molecules at AZs in Drosophila photoreceptors. Using image analysis software, clusters of the GFP-fused AZ component Bruchpilot were identified for each R8 photoreceptor (R8) axon terminal. Detected Bruchpilot spots were automatically assigned to individual R8 axons. To calculate the distribution of spot frequency along the axon, we implemented a customized software plugin. Each axon's start-point and end-point were manually defined and the position of each Bruchpilot spot was projected onto the connecting line between start and end-point. Besides the number of Bruchpilot clusters, we also quantified the delocalization level of Bruchpilot-GFP within the clusters. These measurements reflect in detail the spatially resolved synaptic dynamics in a single neuron under different environmental conditions to stimuli.
- Published
- 2017
29. The gap junction protein Innexin3 is required for eye disc growth in Drosophila
- Author
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Michael Hoch, Reinhard Bauer, Gaia Tavosanis, and Mélisande Richard
- Subjects
0301 basic medicine ,metabolism [Epithelium] ,genetic structures ,Optic Disk ,Optic disk ,metabolism [Drosophila Proteins] ,Innexin ,growth & development [Optic Disk] ,INX3 protein, Drosophila ,Biology ,metabolism [Larva] ,metabolism [Optic Disk] ,Epithelium ,Connexins ,03 medical and health sciences ,anatomy & histology [Optic Disk] ,ddc:570 ,metabolism [Drosophila melanogaster] ,Animals ,Drosophila Proteins ,Molecular Biology ,Cell Proliferation ,Cell growth ,Cell Biology ,Compound eye ,Anatomy ,Organ Size ,metabolism [Connexins] ,biology.organism_classification ,eye diseases ,Cell biology ,030104 developmental biology ,Drosophila melanogaster ,Phenotype ,Larva ,Eye development ,sense organs ,Signal transduction ,growth & development [Drosophila melanogaster] ,Drosophila Protein ,Developmental Biology ,Signal Transduction - Abstract
The Drosophila compound eye develops from a bilayered epithelial sac composed of an upper peripodial epithelium layer and a lower disc proper, the latter giving rise to the eye itself. During larval stages, complex signalling events between the layers contribute to the control of cell proliferation and differentiation in the disc. Previous work in our lab established the gap junction protein Innexin2 (Inx2) as crucial for early larval eye disc growth. By analysing the contribution of other Innexins to eye size control, we have identified Innexin3 (Inx3) as an important growth regulator. Depleting inx3 during larval eye development reduces eye size, while elevating inx3 levels increases eye size, thus phenocopying the inx2 loss- and gain-of-function situation. As demonstrated previously for inx2, inx3 regulates disc cell proliferation and interacts genetically with the Dpp pathway, being required for the proper activation of the Dpp pathway transducer Mad at the furrow and the expression of Dpp receptor Punt in the eye disc. At the developmental timepoint corresponding to eye disc growth, Inx3 colocalises with Inx2 in disc proper and peripodial epithelium cell membranes. In addition, we show that Inx3 protein levels critically depend on inx2 throughout eye development and that inx3 modulates Inx2 protein levels in the larval eye disc. Rescue experiments demonstrate that Inx3 and Inx2 cooperate functionally to enable eye disc growth in Drosophila. Finally, we demonstrate that expression of Inx3 and Inx2 is not only needed in the disc proper but also in the peripodial epithelium to regulate growth of the eye disc. Our data provide a functional demonstration that putative Inx2/Inx3 heteromeric channels regulate organ size.
- Published
- 2017
30. Cell-Autonomous Control of Neuronal Dendrite Expansion via the Fatty Acid Synthesis Regulator SREBP
- Author
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Philipp Leyendecker, Peter Soba, Anna B. Ziegler, Gaia Tavosanis, Federico Tenedini, Astrid Hoermann, Mélisande Richard, and Christoph Thiele
- Subjects
0301 basic medicine ,Nociception ,metabolism [Sterol Regulatory Element Binding Proteins] ,genetics [Sterol Regulatory Element Binding Proteins] ,Mutant ,Neuronal Outgrowth ,Regulator ,Dendrite ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,metabolism [Fatty Acids] ,Animals ,metabolism [Dendrites] ,ddc:610 ,lcsh:QH301-705.5 ,Fatty acid synthesis ,chemistry.chemical_classification ,Sterol Regulatory Element Binding Proteins ,Fatty Acids ,Fatty acid ,Metabolism ,physiology [Dendrites] ,Sterol regulatory element-binding protein ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,lcsh:Biology (General) ,nervous system ,chemistry ,lipids (amino acids, peptides, and proteins) ,Drosophila ,030217 neurology & neurosurgery ,Function (biology) - Abstract
Summary: During differentiation, neurons require a high lipid supply for membrane formation as they elaborate complex dendritic morphologies. While glia-derived lipids support neuronal growth during development, the importance of cell-autonomous lipid production for dendrite formation has been unclear. Using Drosophila larva dendritic arborization (da) neurons, we show that dendrite expansion relies on cell-autonomous fatty acid production. The nociceptive class four (CIV) da neurons form particularly large space-filling dendrites. We show that dendrite formation in these CIVda neurons additionally requires functional sterol regulatory element binding protein (SREBP), a crucial regulator of fatty acid production. The dendrite simplification in srebp mutant CIVda neurons is accompanied by hypersensitivity of srebp mutant larvae to noxious stimuli. Taken together, our work reveals that cell-autonomous fatty acid production is required for proper dendritic development and establishes the role of SREBP in complex neurons for dendrite elaboration and function. : Ziegler et al. highlight the endogenous role of fatty acid synthesis for proper neuronal dendrite growth during development. Using Drosophila da neurons, they show that large CIVda neurons cell-autonomously rely on fatty acid synthesis through the lipid synthesis master regulator SREBP. Keywords: Drosophila, dendrite differentiation, fatty acids, lipids, SREBP, metabolism, brain, nociception
- Published
- 2017
31. Presynapses in Kenyon cell dendrites in the mushroom body calyx of Drosophila
- Author
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Carolin Wichmann, Till F. M. Andlauer, Frauke Christiansen, Wernher Fouquet, Gaia Tavosanis, Christina Zube, Florian Leiss, Abud J. Farca Luna, Stephan J. Sigrist, David Owald, Sara Mertel, and André Fiala
- Subjects
Neurons ,Olfactory system ,Microscopy, Confocal ,Kenyon cell ,General Neuroscience ,Stimulation ,Articles ,Dendrites ,Biology ,biology.organism_classification ,Immunohistochemistry ,eye diseases ,Calyx ,Postsynaptic potential ,Synapses ,Mushroom bodies ,Animals ,Drosophila ,Synaptic Vesicles ,Olfactory Learning ,Neuroscience ,Mushroom Bodies - Abstract
Plastic changes at the presynaptic sites of the mushroom body (MB) principal neurons called Kenyon cells (KCs) are considered to represent a neuronal substrate underlying olfactory learning and memory. It is generally believed that presynaptic and postsynaptic sites of KCs are spatially segregated. In the MB calyx, KCs receive olfactory input from projection neurons (PNs) on their dendrites. Their presynaptic sites, however, are thought to be restricted to the axonal projections within the MB lobes. Here, we show that KCs also form presynapses along their calycal dendrites, by using novel transgenic tools for visualizing presynaptic active zones and postsynaptic densities. At these presynapses, vesicle release following stimulation could be observed. They reside at a distance from the PN input into the KC dendrites, suggesting that regions of presynaptic and postsynaptic differentiation are segregated along individual KC dendrites. KC presynapses are present in γ-type KCs that support short- and long-term memory in adult flies and larvae. They can also be observed in α/β-type KCs, which are involved in memory retrieval, but not in α'/β'-type KCs, which are implicated in memory acquisition and consolidation. We hypothesize that, as in mammals, recurrent activity loops might operate for memory retrieval in the fly olfactory system. The newly identified KC-derived presynapses in the calyx are, inter alia, candidate sites for the formation of memory traces during olfactory learning.
- Published
- 2016
32. Rotating for elongation: Fat2 whips for the race
- Author
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Gaia Tavosanis and Tomke Stürner
- Subjects
0301 basic medicine ,Cell ,Morphogenesis ,metabolism [Multiprotein Complexes] ,Motility ,Reviews ,metabolism [Drosophila Proteins] ,03 medical and health sciences ,cytology [Drosophila melanogaster] ,Cell Movement ,ddc:570 ,metabolism [Drosophila melanogaster] ,medicine ,Animals ,Drosophila Proteins ,Cytoskeleton ,Actin ,biology ,Cadherin ,Comment ,metabolism [Cadherins] ,Cell Biology ,biology.organism_classification ,Actin cytoskeleton ,Cadherins ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Multiprotein Complexes ,Drosophila melanogaster - Abstract
Dynamic rearrangements of the actin cytoskeleton are crucial for cell shape and migration. In this issue, Squarr et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201508081) show that the cadherin superfamily protein Fat2 regulates actin-rich protrusions driving collective cell migration during Drosophila melanogaster egg morphogenesis through its interaction with the WAVE regulatory complex.
- Published
- 2016
33. Fascin controls neuronal class-specific dendrite arbor morphology
- Author
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Yun Zhang, Adrian W. Moore, Julia Nagel, Gaia Tavosanis, Caroline Delandre, and Friedrich Forstner
- Subjects
Nerve net ,Genes, Insect ,genetics [Carrier Proteins] ,Animals, Genetically Modified ,genetics [Drosophila Proteins] ,metabolism [Homeodomain Proteins] ,metabolism [Drosophila melanogaster] ,ultrastructure [Dendrites] ,Drosophila Proteins ,metabolism [Transcription Factors] ,Phosphorylation ,metabolism [Nerve Net] ,growth & development [Larva] ,genetics [Drosophila melanogaster] ,Microfilament Proteins ,Neurogenesis ,classification [Sensory Receptor Cells] ,Nuclear Proteins ,genetics [Nuclear Proteins] ,Cell migration ,chemistry [Carrier Proteins] ,physiology [Neurogenesis] ,genetics [Transcription Factors] ,growth & development [Nerve Net] ,Cell biology ,Drosophila melanogaster ,medicine.anatomical_structure ,genetics [Neurogenesis] ,Larva ,chemistry [Drosophila Proteins] ,metabolism [Nuclear Proteins] ,Sensory Receptor Cells ,genetics [Homeodomain Proteins] ,metabolism [Drosophila Proteins] ,Dendrite ,Sensory system ,macromolecular substances ,metabolism [Larva] ,fascin ,Biology ,ddc:570 ,medicine ,metabolism [Sensory Receptor Cells] ,Animals ,metabolism [Dendrites] ,chemistry [Microfilament Proteins] ,Molecular Biology ,Transcription factor ,Fascin ,Homeodomain Proteins ,ct protein, Drosophila ,metabolism [Microfilament Proteins] ,Dendrites ,nervous system ,biology.protein ,growth & development [Drosophila melanogaster] ,genetics [Microfilament Proteins] ,Nerve Net ,Carrier Proteins ,metabolism [Carrier Proteins] ,ultrastructure [Sensory Receptor Cells] ,Transcription Factors ,Developmental Biology - Abstract
The branched morphology of dendrites represents a functional hallmark of distinct neuronal types. Nonetheless, how diverse neuronal class-specific dendrite branches are generated is not understood. We investigated specific classes of sensory neurons of Drosophila larvae to address the fundamental mechanisms underlying the formation of distinct branch types. We addressed the function of fascin, a conserved actin-bundling protein involved in filopodium formation, in class III and class IV sensory neurons. We found that the terminal branchlets of different classes of neurons have distinctive dynamics and are formed on the basis of molecularly separable mechanisms; in particular, class III neurons require fascin for terminal branching whereas class IV neurons do not. In class III neurons, fascin controls the formation and dynamics of terminal branchlets. Previous studies have shown that transcription factor combinations define dendrite patterns; we find that fascin represents a downstream component of such programs, as it is a major effector of the transcription factor Cut in defining class III-specific dendrite morphology. Furthermore, fascin defines the morphological distinction between class III and class IV neurons. In fact, loss of fascin function leads to a partial conversion of class III neurons to class IV characteristics, while the reverse effect is obtained by fascin overexpression in class IV neurons. We propose that dedicated molecular mechanisms underlie the formation and dynamics of distinct dendrite branch types to elicit the accurate establishment of neuronal circuits.
- Published
- 2012
34. Structural Long-Term Changes at Mushroom Body Input Synapses
- Author
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Florian Leiss, Peter Kloppenburg, Gaia Tavosanis, Till F. M. Andlauer, Stephan J. Sigrist, Frauke Christiansen, Friedrich Forstner, Moritz Paehler, Stephan Knapek, and Malte C. Kremer
- Subjects
Potassium Channels ,Recombinant Fusion Proteins ,Action Potentials ,Sensory system ,Cellular level ,Neurotransmission ,Biology ,Synaptic Transmission ,General Biochemistry, Genetics and Molecular Biology ,Calyx ,Postsynaptic potential ,Animals ,Drosophila Proteins ,Active zone ,Mushroom Bodies ,Neurons ,Agricultural and Biological Sciences(all) ,Biochemistry, Genetics and Molecular Biology(all) ,fungi ,Anatomy ,Smell ,Brain region ,nervous system ,Synapses ,Mushroom bodies ,Drosophila ,General Agricultural and Biological Sciences ,Neuroscience - Abstract
SummaryHow does the sensory environment shape circuit organization in higher brain centers? Here we have addressed the dependence on activity of a defined circuit within the mushroom body of adult Drosophila. This is a brain region receiving olfactory information and involved in long-term associative memory formation [1]. The main mushroom body input region, named the calyx, undergoes volumetric changes correlated with alterations of experience [2–5]. However, the underlying modifications at the cellular level remained unclear. Within the calyx, the clawed dendritic endings of mushroom body Kenyon cells form microglomeruli, distinct synaptic complexes with the presynaptic boutons of olfactory projection neurons [6, 7]. We developed tools for high-resolution imaging of pre- and postsynaptic compartments of defined calycal microglomeruli. Here we show that preventing firing of action potentials or synaptic transmission in a small, identified fraction of projection neurons causes alterations in the size, number, and active zone density of the microglomeruli formed by these neurons. These data provide clear evidence for activity-dependent organization of a circuit within the adult brain of the fly.
- Published
- 2010
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35. Synaptic organization in the adultDrosophilamushroom body calyx
- Author
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Ian A. Meinertzhagen, Nancy J. Butcher, Gaia Tavosanis, Claudia Groh, and Florian Leiss
- Subjects
Models, Anatomic ,Olfactory system ,Kenyon cell ,Presynaptic Terminals ,Dendrite ,Biology ,Filamentous actin ,Calyx ,Neural Pathways ,medicine ,Animals ,Drosophila Proteins ,Mushroom Bodies ,Neurons ,Microscopy, Confocal ,Glutamate Decarboxylase ,General Neuroscience ,fungi ,Dendrites ,Immunohistochemistry ,Actins ,Associative learning ,Microscopy, Electron ,medicine.anatomical_structure ,nervous system ,Synapses ,Mushroom bodies ,Drosophila ,Antennal lobe ,Neuroscience - Abstract
Insect mushroom bodies are critical for olfactory associative learning. We have carried out an extensive quantitative description of the synaptic organization of the calyx of adult Drosophila melanogaster, the main olfactory input region of the mushroom body. By using high-resolution confocal microscopy, electron microscopy-based three-dimensional reconstructions, and genetic labeling of the neuronal populations contributing to the calyx, we resolved the precise connections between large cholinergic boutons of antennal lobe projection neurons and the dendrites of Kenyon cells, the mushroom body intrinsic neurons. Throughout the calyx, these elements constitute synaptic complexes called microglomeruli. By single-cell labeling, we show that each Kenyon cell's claw-like dendritic specialization is highly enriched in filamentous actin, suggesting that this might be a site of plastic reorganization. In fact, Lim kinase (LimK) overexpression in the Kenyon cells modifies the shape of the microglomeruli. Confocal and electron microscopy indicate that each Kenyon cell claw enwraps a single bouton of a projection neuron. Each bouton is contacted by a number of such claw-like specializations as well as profiles of gamma-aminobutyric acid-positive neurons. The dendrites of distinct populations of Kenyon cells involved in different types of memory are partially segregated within the calyx and contribute to different subsets of microglomeruli. Our analysis suggests, though, that projection neuron boutons can contact more than one type of Kenyon cell. These findings represent an important basis for the functional analysis of the olfactory pathway, including the formation of associative olfactory memories.
- Published
- 2009
36. Slit and Robo regulate dendrite branching and elongation of space-filling neurons in Drosophila
- Author
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André Reissaus, Gaia Tavosanis, and Svetla Dimitrova
- Subjects
Embryo, Nonmammalian ,Mutant ,PNS ,Nerve Tissue Proteins ,Dendrite ,Robo ,Biology ,Branching (polymer chemistry) ,Slit ,Peripheral Nervous System ,medicine ,Animals ,Drosophila Proteins ,Receptors, Immunologic ,Molecular Biology ,Process (anatomy) ,Neurons ,Cell Differentiation ,Dendrites ,Cell Biology ,Anatomy ,Embryonic stem cell ,Cell biology ,Drosophila melanogaster ,medicine.anatomical_structure ,nervous system ,Receptive field ,Larva ,Mutation ,Drosophila ,Elongation ,Developmental Biology - Abstract
Space-filling neurons extensively sample their receptive fields with fine dendritic branches. In this study we show that a member of the conserved Robo receptor family, Robo, and its ligand Slit regulate the dendritic differentiation of space-filling neurons. Loss of Robo or Slit function leads to faster elongating and less branched dendrites of the complex and space-filling class IV multi-dendritic dendrite-arborization (md-da) neurons in the Drosophila embryonic peripheral nervous system, but not of the simpler class I neurons. The total dendrite length of Class IV neurons is not modified in robo or slit mutant embryos. Robo mediates this process cell-autonomously. Upon Robo over-expression in md-da neurons the dendritic tree is simplified and time-lapse analysis during larval stages indicates that this is due to reduction in the number of newly formed branches. We propose that Slit, through Robo, provides an extrinsic signal to coordinate the growth rate and the branching level of space-filling neurons, thus allowing them to appropriately cover their target field.
- Published
- 2008
37. Steroid Hormone Ecdysone Signaling Specifies Mushroom Body Neuron Sequential Fate via Chinmo
- Author
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Giovanni Marchetti and Gaia Tavosanis
- Subjects
0301 basic medicine ,Receptors, Steroid ,Kenyon cell ,medicine.medical_treatment ,Regulator ,ecdysone receptor ,genetics [Larva] ,chemistry.chemical_compound ,genetics [Drosophila Proteins] ,genetics [Receptors, Steroid] ,metabolism [Drosophila melanogaster] ,growth & development [Pupa] ,Drosophila Proteins ,genetics [Nerve Tissue Proteins] ,growth & development [Larva] ,Neurons ,genetics [Drosophila melanogaster] ,metabolism [Pupa] ,Pupa ,Gene Expression Regulation, Developmental ,Cell Differentiation ,physiology [Neurons] ,Cell biology ,Drosophila melanogaster ,medicine.anatomical_structure ,Larva ,Mushroom bodies ,metabolism [Ecdysone] ,General Agricultural and Biological Sciences ,Ecdysone ,Signal Transduction ,medicine.medical_specialty ,metabolism [Drosophila Proteins] ,Nerve Tissue Proteins ,metabolism [Larva] ,Biology ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,ddc:570 ,Internal medicine ,medicine ,Animals ,Transcription factor ,Mushroom Bodies ,growth & development [Mushroom Bodies] ,genetics [Pupa] ,metabolism [Nerve Tissue Proteins] ,metabolism [Receptors, Steroid] ,Chinmo protein, Drosophila ,Steroid hormone ,030104 developmental biology ,Endocrinology ,chemistry ,Neuron ,growth & development [Drosophila melanogaster] ,Ecdysone receptor - Abstract
The functional variety in neuronal composition of an adult brain is established during development. Recent studies proposed that interactions between genetic intrinsic programs and external cues are necessary to generate proper neural diversity [1]. However, the molecular mechanisms underlying this developmental process are still poorly understood. Three main subtypes of Drosophila mushroom body (MB) neurons are sequentially generated during development and provide a good example of developmental neural plasticity [2]. Our present data propose that the environmentally controlled steroid hormone ecdysone functions as a regulator of early-born MB neuron fate during larval-pupal transition. We found that the BTB-zinc finger factor Chinmo acts upstream of ecdysone signaling to promote a neuronal fate switch. Indeed, Chinmo regulates the expression of the ecdysone receptor B1 isoform to mediate the production of γ and α'β' MB neurons. In addition, we provide genetic evidence for a regulatory negative feedback loop driving the α'β' to αβ MB neuron transition in which ecdysone signaling in turn controls microRNA let-7 depression of Chinmo expression. Thus, our results uncover a novel interaction in the MB neural specification pathway for temporal control of neuronal identity by interplay between an extrinsic hormonal signal and an intrinsic transcription factor cascade.
- Published
- 2017
38. 6DMAP inhibition of early cell cycle events and induction of mitotic abnormalities
- Author
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Louis de Saint-Georges, Simona Pigullo, Paola Pellerano, Marcella Simili, Gaia Tavosanis, Stefania Bonatti, and Laura Ottaggio
- Subjects
Ribosomal Proteins ,medicine.drug_class ,Health, Toxicology and Mutagenesis ,Mitosis ,P70-S6 Kinase 1 ,Biology ,Toxicology ,Cell Line ,Cricetulus ,Epidermal growth factor ,Cricetinae ,Genetics ,medicine ,Animals ,Enzyme Inhibitors ,Phosphorylation ,Cytoskeleton ,Genetics (clinical) ,Chromosome Aberrations ,Ribosomal Protein S6 ,Micronucleus Tests ,Kinase ,Adenine ,Ribosomal Protein S6 Kinases ,Cell Cycle ,DNA ,Fibroblasts ,Cell cycle ,Protein kinase inhibitor ,Cell biology ,Mutagenesis ,Ribosomal protein s6 ,Calcium-Calmodulin-Dependent Protein Kinases ,Signal transduction - Abstract
N-6 dimethylaminopurine (6DMAP) has been shown to induce aberrant mitosis in different cell types including Chinese hamster fibroblasts (CHEF/18), The mechanism of action and the cellular targets, however, are still not clear, We showed previously that in CHEF/18 cells this compound inhibits DNA synthesis with a kinetic of inhibition suggestive of an effect on early events of the cell cycle, In this paper we investigated which cellular targets were affected by 6DMAP and found that: (i) the compound inhibits phosphorylation of ribosomal protein S6 and activation of the 70 kDa S6 kinase (p70(S6k)) known to be activated by epidermal growth factor (EGF) in keeping with the notion that it is a protein kinase inhibitor; however the inhibition in vivo appears to be specific as MAP kinase phosphorylation is not inhibited; (ii) 6DMAP drastically affects cytoskeletal components leading to a rapid morphological change in most cells. These data, together with the findings that the dose range and the treatment time effective in inducing the micronuclei containing chromosomes were the same as for DNA synthesis inhibition, suggest that a disturbance in G(1) of signal transduction pathways may contribute to abnormal mitosis.
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- 1997
39. The Cell Biology of Dendrite Differentiation
- Author
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Gaia Tavosanis
- Subjects
medicine.anatomical_structure ,nervous system ,medicine ,Dendrite ,Neuron ,Biology ,Cytoskeleton ,Process (anatomy) ,Function (biology) ,Cell biology - Abstract
The morphology of neuronal dendrites defines the position and extent of input connections that a neuron receives and influences computational aspects of input processing. Establishing appropriate dendrite morphology thus underscores proper neuronal function. Indeed, inappropriate patterning of dendrites is a common feature of conditions that lead to mental retardation. Here, we explore the basic mechanisms that lead to the formation of branched dendrites and the cell biological aspects that underlie this complex process. We summarize some of the major steps that from developmental transcriptional regulation and environmental information modulate the neuron’s cytoskeleton to obtain the arborized structures that have fascinated neuroscientists for more than a century.
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- 2013
40. Assessing the role of cell-surface molecules in central synaptogenesis in the Drosophila visual system
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Fumio Takahashi, Gaia Tavosanis, Atsushi Sugie, Sandra Berger-Müller, Satoko Hakeda-Suzuki, and Takashi Suzuki
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Science ,Synaptogenesis ,Gene Expression ,Neurotransmission ,Biology ,metabolism [Axons] ,Synaptic Transmission ,Presynapse ,Synapse ,Animals, Genetically Modified ,Axon terminal ,medicine ,Animals ,ddc:610 ,Axon ,Multidisciplinary ,Synaptic pharmacology ,Membrane Proteins ,Axons ,Cell biology ,genetics [Membrane Proteins] ,medicine.anatomical_structure ,physiology [Synaptic Transmission] ,Medicine ,Axon guidance ,Drosophila ,Photoreceptor Cells, Invertebrate ,physiology [Photoreceptor Cells, Invertebrate] ,physiology [Drosophila] ,metabolism [Membrane Proteins] ,Research Article - Abstract
A hallmark of the central nervous system is its spatial and functional organization in synaptic layers. During neuronal development, axons form transient contacts with potential post-synaptic elements and establish synapses with appropriate partners at specific layers. These processes are regulated by synaptic cell-adhesion molecules. In the Drosophila visual system, R7 and R8 photoreceptor subtypes target distinct layers and form en passant pre-synaptic terminals at stereotypic loci of the axonal shaft. A leucine-rich repeat transmembrane protein, Capricious (Caps), is known to be selectively expressed in R8 axons and their recipient layer, which led to the attractive hypothesis that Caps mediates R8 synaptic specificity by homophilic adhesion. Contradicting this assumption, our results indicate that Caps does not have a prominent role in synaptic-layer targeting and synapse formation in Drosophila photoreceptors, and that the specific recognition of the R8 target layer does not involve Caps homophilic axon-target interactions. We generated flies that express a tagged synaptic marker to evaluate the presence and localization of synapses in R7 and R8 photoreceptors. These genetic tools were used to assess how the synaptic profile is affected when axons are forced to target abnormal layers by expressing axon guidance molecules. When R7 axons were mistargeted to the R8-recipient layer, R7s either maintained an R7-like synaptic profile or acquired a similar profile to r8s depending on the overexpressed protein. When R7 axons were redirected to a more superficial medulla layer, the number of presynaptic terminals was reduced. These results indicate that cell-surface molecules are able to dictate synapse loci by changing the axon terminal identity in a partially cell-autonomous manner, but that presynapse formation at specific sites also requires complex interactions between pre- and post-synaptic elements.
- Published
- 2013
41. Dendritic structural plasticity
- Author
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Gaia Tavosanis
- Subjects
ultrastructure [Neurons] ,Neurons ,Neuronal Plasticity ,Dendrite ,Cell Differentiation ,physiology [Dendrites] ,Dendrites ,Plasticity ,Biology ,Cellular and Molecular Neuroscience ,Adult life ,medicine.anatomical_structure ,Developmental Neuroscience ,Structural plasticity ,medicine ,Compartment (development) ,physiology [Neuronal Plasticity] ,Animals ,Causal link ,Neuron ,ddc:610 ,Process (anatomy) ,Neuroscience - Abstract
Dendrites represent the compartment of neurons primarily devoted to collecting and computating input. Far from being static structures, dendrites are highly dynamic during development and appear to be capable of plastic changes during the adult life of animals. During development, it is a combination of intrinsic programs and external signals that shapes dendrite morphology; input activity is a conserved extrinsic factor involved in this process. In adult life, dendrites respond with more modest modifications of their structure to various types of extrinsic information, including alterations of input activity. Here, the author reviews classical and recent evidence of dendrite plasticity in invertebrates and vertebrates and current progress in the understanding of the molecular mechanisms that underlie this plasticity. Importantly, some fundamental questions such as the functional role of dendrite remodeling and the causal link between structural modifications of neurons and plastic processes, including learning, are still open. © 2011 Wiley Periodicals, Inc. Develop Neurobiol 72: 73–86, 2012
- Published
- 2011
42. Characterization of dendritic spines in the Drosophila central nervous system
- Author
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Stephan J. Sigrist, Wernher Fouquet, Irina Hein, Gaia Tavosanis, Ewa Koper, Jana Lindner, and Florian Leiss
- Subjects
Nervous system ,Central Nervous System ,Dendritic spine ,Microscopy, Confocal ,Dendritic Spines ,Central nervous system ,Biology ,Immunohistochemistry ,Polymerase Chain Reaction ,Actins ,Dendritic filopodia ,Cellular and Molecular Neuroscience ,Actin remodeling of neurons ,Microscopy, Electron ,medicine.anatomical_structure ,Developmental Neuroscience ,Interneurons ,Tubulin ,medicine ,Excitatory postsynaptic potential ,Animals ,Small GTPase ,Drosophila ,Neuroscience ,Actin - Abstract
Dendritic spines are a characteristic feature of a number of neurons in the vertebrate nervous system and have been implicated in processes that include learning and memory. In spite of this, there has been no comprehensive analysis of the presence of spines in a classical genetic system, such as Drosophila, so far. Here, we demonstrate that a subset of processes along the dendrites of visual system interneurons in the adult fly central nervous system, called LPTCs, closely resemble vertebrate spines, based on a number of criteria. First, the morphology, size, and density of these processes are very similar to those of vertebrate spines. Second, they are enriched in actin and devoid of tubulin. Third, they are sites of synaptic connections based on confocal and electron microscopy. Importantly, they represent a preferential site of localization of an acetylcholine receptor subunit, suggesting that they are sites of excitatory synaptic input. Finally, their number is modulated by the level of the small GTPase dRac1. Our results provide a basis to dissect the genetics of dendritic spine formation and maintenance and the functional role of spines. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2009
- Published
- 2009
43. gamma-Tubulin function during female germ-cell development and oogenesis in Drosophila
- Author
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Cayetano Gonzalez and Gaia Tavosanis
- Subjects
Genetics ,Multidisciplinary ,Mutant ,Mitosis ,macromolecular substances ,Biology ,Biological Sciences ,Oocyte ,Oogenesis ,medicine.anatomical_structure ,Tubulin ,Microtubule ,medicine ,biology.protein ,Oocytes ,Animals ,Drosophila ,Female ,Gene ,Germ cell - Abstract
A series of unconventional microtubule organizing centers play a fundamental role during egg chamber development in Drosophila . To gain a better understanding of their molecular nature, we have studied the centrosomal component γ-tubulin during Drosophila oogenesis. We find that although single mutations in either of the two γ-tubulin genes identified in Drosophila do not affect oogenesis progression the simultaneous depletion of both protein products has severe consequences. The combination of loss-of-function mutant alleles for the two γ-tubulin genes leads to mitotic defects in female germ cells, resulting in agametic ovaries. A combination of weaker mutant alleles instead allows female germ-cell development to proceed, although the resulting egg chambers display pleiotropic abnormalities, most frequently affecting the number of nurse cells and oocytes per egg chamber. Thus, γ-tubulin is required for several processes at different stages of germ-cell development and oogenesis, including oocyte determination and differentiation. Our data provide a functional link between a component of the peri-centriolar material, such as γ-tubulin, and microtubule organization during Drosophila oogenesis. In addition, our results show that γ-tubulin is required for female germcell proliferation and that the two γ-tubulins present in Drosophila are functionally equivalent during female germ-cell development and oogenesis.
- Published
- 2003
44. Essential role for gamma-tubulin in the acentriolar female meiotic spindle of Drosophila
- Author
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Gaia Tavosanis, Cayetano Gonzalez, Salud Llamazares, and George Goulielmos
- Subjects
Gene isoform ,Embryo, Nonmammalian ,Molecular Sequence Data ,Spindle Apparatus ,Microtubules ,General Biochemistry, Genetics and Molecular Biology ,Oogenesis ,Meiosis ,Microtubule ,Tubulin ,Melanogaster ,Animals ,RNA, Messenger ,Molecular Biology ,Microtubule nucleation ,Centrosome ,General Immunology and Microbiology ,biology ,Base Sequence ,General Neuroscience ,Ovary ,Gene Expression Regulation, Developmental ,Microtubule organizing center ,biology.organism_classification ,Molecular biology ,Drosophila melanogaster ,Phenotype ,Mutation ,Oocytes ,Female ,Infertility, Female ,Research Article - Abstract
Microtubule nucleation in vivo requires gamma-tubulin, a highly conserved component of microtubule-organizing centers. In Drosophila melanogaster there are two gamma-tubulin genes, gammaTUB23C and gammaTUB37C. Here we report the cytological and molecular characterization of the 37C isoform. By Western blotting, this protein can only be detected in ovaries and embryos. Antibodies against this isoform predominantly label the centrosomes in embryos from early cleavage divisions until cycle 15, but fail to reveal any particular localization of gamma-tubulin in the developing egg chambers. The loss of function of this gene results in female sterility and has no effect on viability or male fertility. Early stages of oogenesis are unaffected by mutations in this gene, as judged both by morphological criteria and by localization of reporter genes, but the female meiotic spindle is extremely disrupted. Nuclear proliferation within the eggs laid by mutant females is also impaired. We conclude that the expression of the 37C gamma-tubulin isoform of D. melanogaster is under strict developmental regulation and that the organization of the female meiotic spindle requires gamma-tubulin.
- Published
- 1997
45. The induction of aneuploidy by alkylated purines: effects on early and late cell cycle events
- Author
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Marcella Simili, Gaia Tavosanis, Guiseppe Arena, Angelo Abbondandolo, Paola Pellerano, and Stefania Bonatti
- Subjects
Time Factors ,Alkylation ,Health, Toxicology and Mutagenesis ,Cell ,Mitosis ,Biology ,Toxicology ,3T3 cells ,S Phase ,Mice ,Cricetulus ,Epidermal growth factor ,Cricetinae ,Genetics ,medicine ,Animals ,Insulin ,Growth Substances ,Genetics (clinical) ,Cells, Cultured ,Chromosome Aberrations ,Cyclin-dependent kinase 1 ,DNA synthesis ,Cell Cycle ,G1 Phase ,3T3 Cells ,DNA ,Cell cycle ,Fibroblasts ,Aneuploidy ,Embryo, Mammalian ,Molecular biology ,medicine.anatomical_structure ,Cell culture ,Purines ,Female - Abstract
It has been shown that alkylated bases induce aneuploidy in mammalian cells in culture. The mechanism of action is not clear, however, data with 6-dimethyl amino purine (6DMAP) suggest that this analogue might act by affecting the cytoskeleton and protein kinases involved in cell cycle regulation (cdc2/p34). The aim of this work was to study the effect of O 6 methylguanine (O 6 meG), O 6 ethylguanine (O 6 etG) and 6DMAP on DNA synthesis induced by growth factors in two cell lines, 3T3 and CHEF/18 fibroblasts, which respond in opposite ways to substances affecting the cytoskeleton, colchicine and cholera toxin: DNA synthesis initiation is stimulated in 3T3 cells and inhibited in CHEF/18 cells by such compounds. Our results indicate that O 6 meG and O 6 etG behave like cholera toxin, in as much as they inhibit DNA synthesis induced by epidermal growth factor plus insulin in CHEF/18 cells, and stimulate it in 3T3 cells. 6DMAP behaves differently and inhibits DNA synthesis in both cell lines. The inhibition (or stimulation) was greater when alkylated bases were added before S phase started, suggesting that these compounds might affect early events of the cell cycle. In CHEF/18 cells the three alkylated bases were able to induce aberrant metaphases and ana-telophases with different efficiency (70-100%). The effect was not dependent on the G 1 -S block and it was reversible even after cell commitment to DNA synthesis
- Published
- 1995
46. The Drosophila Myosin VI Jaguar Is Required for Basal Protein Targeting and Correct Spindle Orientation in Mitotic Neuroblasts
- Author
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Christoph W. Turck, Lily Yeh Jan, Gaia Tavosanis, Yuh Nung Jan, and Claudia Petritsch
- Subjects
Embryo, Nonmammalian ,animal structures ,Immunoblotting ,Cell Cycle Proteins ,Spindle Apparatus ,Cell fate determination ,Biology ,medicine.disease_cause ,General Biochemistry, Genetics and Molecular Biology ,Immunoenzyme Techniques ,Neuroblast ,Cell Movement ,Protein targeting ,Myosin ,medicine ,Animals ,Drosophila Proteins ,Molecular Biology ,Mitosis ,Actin ,Neurons ,Myosin Heavy Chains ,Neuropeptides ,Intracellular Signaling Peptides and Proteins ,Signal transducing adaptor protein ,Cell Polarity ,Biological Transport ,Cell Differentiation ,Cell Biology ,Cell biology ,Cytoskeletal Proteins ,Drosophila melanogaster ,embryonic structures ,RNA Interference ,Apical complex ,Carrier Proteins ,Cell Division ,Developmental Biology - Abstract
Asymmetric cell divisions generate cellular diversity. In Drosophila , embryonic neuroblasts target cell fate determinants basally, rotate their spindles by 90° to align with the apical-basal axis, and divide asymmetrically in a stem cell-like fashion. In this process, apically localized Bazooka recruits Inscuteable and other proteins to form an apical complex, which then specifies spindle orientation and basal localization of the cell fate determinants and their adapter proteins such as Miranda. Here we report that Miranda localization requires the unconventional myosin VI Jaguar (Jar). In jar null mutant embryos, Miranda is delocalized and the spindle is misoriented, but the Inscuteable crescent remains apical. Miranda directly binds to Jar, raising the possibility that Miranda and its associated proteins are translocated basally by this actin-based motor. Our studies demonstrate that a class VI myosin is necessary for basal protein targeting and spindle orientation in neuroblasts.
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47. Molecular Remodeling of the Presynaptic Active Zone of Drosophila Photoreceptors via Activity-Dependent Feedback
- Author
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Atsushi Sugie, Takashi Suzuki, Satoko Hakeda-Suzuki, Gaia Tavosanis, Emiko Suzuki, Mai Shimozono, Marion Silies, and Christoph Möhl
- Subjects
Liprin-alpha protein, Drosophila ,GAL4 protein, Drosophila ,genetics [Luminescent Proteins] ,Ion Channels ,genetics [Drosophila Proteins] ,classification [Photoreceptor Cells, Invertebrate] ,Postsynaptic potential ,Drosophila Proteins ,metabolism [Transcription Factors] ,metabolism [Phosphoproteins] ,TRPA1 Cation Channel ,Feedback, Physiological ,General Neuroscience ,Intracellular Signaling Peptides and Proteins ,Wnt signaling pathway ,Depolarization ,ultrastructure [Presynaptic Terminals] ,genetics [Transcription Factors] ,Phenotype ,Drosophila ,Photoreceptor Cells, Invertebrate ,Presynaptic active zone ,Signal Transduction ,TrpA1 protein, Drosophila ,Neuroscience(all) ,metabolism [TRPC Cation Channels] ,BRP protein, Drosophila ,Presynaptic Terminals ,metabolism [Drosophila Proteins] ,Mice, Transgenic ,Sensory system ,physiology [Presynaptic Terminals] ,Biology ,genetics [Signal Transduction] ,Models, Biological ,Microscopy, Electron, Transmission ,Microtubule ,Animals ,ddc:610 ,Active zone ,metabolism [Luminescent Proteins] ,Ion channel ,TRPC Cation Channels ,Phosphoproteins ,metabolism [Photoreceptor Cells, Invertebrate] ,physiology [Feedback, Physiological] ,Luminescent Proteins ,ultrastructure [Synapses] ,Synapses ,sense organs ,physiology [Synapses] ,Neuroscience ,cytology [Photoreceptor Cells, Invertebrate] ,Photic Stimulation ,Transcription Factors - Abstract
SummaryNeural activity contributes to the regulation of the properties of synapses in sensory systems, allowing for adjustment to a changing environment. Little is known about how synaptic molecular components are regulated to achieve activity-dependent plasticity at central synapses. Here, we found that after prolonged exposure to natural ambient light the presynaptic active zone in Drosophila photoreceptors undergoes reversible remodeling, including loss of Bruchpilot, DLiprin-α, and DRBP, but not of DSyd-1 or Cacophony. The level of depolarization of the postsynaptic neurons is critical for the light-induced changes in active zone composition in the photoreceptors, indicating the existence of a feedback signal. In search of this signal, we have identified a crucial role of microtubule meshwork organization downstream of the divergent canonical Wnt pathway, potentially via Kinesin-3 Imac. These data reveal that active zone composition can be regulated in vivo and identify the underlying molecular machinery.
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48. Cytological characterisation of the mutant phenotypes produced during early embryogenesis by null and loss-of-function alleles of the gammaTub37C gene in Drosophila
- Author
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Salud Llamazares, Gaia Tavosanis, and Cayetano Gonzalez
- Subjects
Molecular Sequence Data ,Mutant ,Fluorescent Antibody Technique ,Genes, Insect ,Biology ,medicine.disease_cause ,Microtubules ,Polar body ,Meiosis ,Tubulin ,medicine ,Animals ,Amino Acid Sequence ,Allele ,Gene ,Alleles ,Genetics ,Mutation ,Base Sequence ,Embryo ,Cell Biology ,Phenotype ,Oocytes ,Drosophila ,Female ,DNA Probes - Abstract
We have studied the mutant phenotypes brought about during early embryogenesis by mutation in the gammaTub37C gene, one of the two isoforms of gamma-tubulin that have been identified in Drosophila. We have focused our attention on fs(2)TW1(1) and fs(2)TW1(RU34), a null and a hypomorph allele of this gene, whose sequences we report in this work. We have found that the abnormal meiotic figures observed in mutant stage 14 oocytes are not observed in laid oocytes or fertilised embryos, suggesting that these abnormal meiotic figures are not terminally arrested. We have also concluded that both null and hypomorph alleles lead to a total arrest of nuclear proliferation during early embryogenesis. This is in contrast to their effect on female meiosis-I where hypomorph alleles display a much weaker phenotype. Finally, we have observed that null and hypomorph alleles lead to some distinct phenotypes. Unfertilised laid oocytes and fertilised embryos deficient for gammaTub37C do not contain polar bodies and have a few bipolar microtubule arrays. In contrast, oocytes and embryos from weaker alleles do not have these microtubule arrays, but do contain polar bodies, or polar-body-like structures. These results indicate that gammaTub37C is essential for nuclear proliferation in the early Drosophila embryo.
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