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  • 1
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    Coordinate control of synaptic-layer specificity and rhodopsins in photoreceptor neurons (2008)
    Nature Publishing Group (NPG)
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    Publication Date: 2008-11-04
    Description: How neurons make specific synaptic connections is a central question in neurobiology. The targeting of the Drosophila R7 and R8 photoreceptor axons to different synaptic layers in the brain provides a model with which to explore the genetic programs regulating target specificity. In principle this can be accomplished by cell-type-specific molecules mediating the recognition between synaptic partners. Alternatively, specificity could also be achieved through cell-type-specific repression of particular targeting molecules. Here we show that a key step in the targeting of the R7 neuron is the active repression of the R8 targeting program. Repression is dependent on NF-YC, a subunit of the NF-Y (nuclear factor Y) transcription factor. In the absence of NF-YC, R7 axons terminate in the same layer as R8 axons. Genetic experiments indicate that this is due solely to the derepression of the R8-specific transcription factor Senseless (Sens) late in R7 differentiation. Sens is sufficient to control R8 targeting specificity and we demonstrate that Sens directly binds to an evolutionarily conserved DNA sequence upstream of the start of transcription of an R8-specific cell-surface protein, Capricious (Caps) that regulates R8 target specificity. We show that R7 targeting requires the R7-specific transcription factor Prospero (Pros) in parallel to repression of the R8 targeting pathway by NF-YC. Previous studies demonstrated that Sens and Pros directly regulate the expression of specific rhodopsins in R8 and R7. We propose that the use of the same transcription factors to promote the cell-type-specific expression of sensory receptors and cell-surface proteins regulating synaptic target specificity provides a simple and general mechanism for ensuring that transmission of sensory information is processed by the appropriate specialized neural circuits.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2727603/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2727603/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morey, Marta -- Yee, Susan K -- Herman, Tory -- Nern, Aljoscha -- Blanco, Enrique -- Zipursky, S Lawrence -- GM7185/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Dec 11;456(7223):795-9. doi: 10.1038/nature07419.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry, Howard Hughes Medical Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18978774" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Compound Eye, Arthropod/growth & development/metabolism ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster/genetics/*physiology ; *Gene Expression Regulation, Developmental ; Membrane Proteins/metabolism ; Mutation ; Nerve Tissue Proteins/metabolism ; Nuclear Proteins/genetics/metabolism ; Photoreceptor Cells, Invertebrate/physiology ; Rhodopsin/*metabolism ; Substrate Specificity ; Synapses/*metabolism ; Transcription Factors/genetics/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    A directional tuning map of Drosophila elementary motion detectors (2013)
    Nature Publishing Group (NPG)
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    Publication Date: 2013-08-09
    Description: The extraction of directional motion information from changing retinal images is one of the earliest and most important processing steps in any visual system. In the fly optic lobe, two parallel processing streams have been anatomically described, leading from two first-order interneurons, L1 and L2, via T4 and T5 cells onto large, wide-field motion-sensitive interneurons of the lobula plate. Therefore, T4 and T5 cells are thought to have a pivotal role in motion processing; however, owing to their small size, it is difficult to obtain electrical recordings of T4 and T5 cells, leaving their visual response properties largely unknown. We circumvent this problem by means of optical recording from these cells in Drosophila, using the genetically encoded calcium indicator GCaMP5 (ref. 2). Here we find that specific subpopulations of T4 and T5 cells are directionally tuned to one of the four cardinal directions; that is, front-to-back, back-to-front, upwards and downwards. Depending on their preferred direction, T4 and T5 cells terminate in specific sublayers of the lobula plate. T4 and T5 functionally segregate with respect to contrast polarity: whereas T4 cells selectively respond to moving brightness increments (ON edges), T5 cells only respond to moving brightness decrements (OFF edges). When the output from T4 or T5 cells is blocked, the responses of postsynaptic lobula plate neurons to moving ON (T4 block) or OFF edges (T5 block) are selectively compromised. The same effects are seen in turning responses of tethered walking flies. Thus, starting with L1 and L2, the visual input is split into separate ON and OFF pathways, and motion along all four cardinal directions is computed separately within each pathway. The output of these eight different motion detectors is then sorted such that ON (T4) and OFF (T5) motion detectors with the same directional tuning converge in the same layer of the lobula plate, jointly providing the input to downstream circuits and motion-driven behaviours.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maisak, Matthew S -- Haag, Juergen -- Ammer, Georg -- Serbe, Etienne -- Meier, Matthias -- Leonhardt, Aljoscha -- Schilling, Tabea -- Bahl, Armin -- Rubin, Gerald M -- Nern, Aljoscha -- Dickson, Barry J -- Reiff, Dierk F -- Hopp, Elisabeth -- Borst, Alexander -- England -- Nature. 2013 Aug 8;500(7461):212-6. doi: 10.1038/nature12320.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute of Neurobiology, 82152 Martinsried, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23925246" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior, Animal/physiology ; Drosophila/cytology/*physiology ; Interneurons/physiology ; Locomotion/physiology ; Motion Perception/*physiology ; Neurons/physiology ; Signal Transduction ; Visual Pathways/cytology/*physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 3
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    A visual motion detection circuit suggested by Drosophila connectomics (2013)
    Nature Publishing Group (NPG)
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    Publication Date: 2013-08-09
    Description: Animal behaviour arises from computations in neuronal circuits, but our understanding of these computations has been frustrated by the lack of detailed synaptic connection maps, or connectomes. For example, despite intensive investigations over half a century, the neuronal implementation of local motion detection in the insect visual system remains elusive. Here we develop a semi-automated pipeline using electron microscopy to reconstruct a connectome, containing 379 neurons and 8,637 chemical synaptic contacts, within the Drosophila optic medulla. By matching reconstructed neurons to examples from light microscopy, we assigned neurons to cell types and assembled a connectome of the repeating module of the medulla. Within this module, we identified cell types constituting a motion detection circuit, and showed that the connections onto individual motion-sensitive neurons in this circuit were consistent with their direction selectivity. Our results identify cellular targets for future functional investigations, and demonstrate that connectomes can provide key insights into neuronal computations.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3799980/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3799980/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takemura, Shin-ya -- Bharioke, Arjun -- Lu, Zhiyuan -- Nern, Aljoscha -- Vitaladevuni, Shiv -- Rivlin, Patricia K -- Katz, William T -- Olbris, Donald J -- Plaza, Stephen M -- Winston, Philip -- Zhao, Ting -- Horne, Jane Anne -- Fetter, Richard D -- Takemura, Satoko -- Blazek, Katerina -- Chang, Lei-Ann -- Ogundeyi, Omotara -- Saunders, Mathew A -- Shapiro, Victor -- Sigmund, Christopher -- Rubin, Gerald M -- Scheffer, Louis K -- Meinertzhagen, Ian A -- Chklovskii, Dmitri B -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Aug 8;500(7461):175-81. doi: 10.1038/nature12450.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Janelia Farm Research Campus, HHMI, Ashburn, Virginia 20147, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23925240" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Connectome ; Drosophila/*physiology ; Female ; *Models, Biological ; Motion Perception/*physiology ; Visual Pathways/cytology/*physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
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    Multiple new site-specific recombinases for use in manipulating animal genomes (2011)
    National Academy of Sciences
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    Publication Date: 2011-08-09
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 5
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    New methods for Drosophila neuroanatomy [Neuroscience] (2015)
    National Academy of Sciences
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    Publication Date: 2015-06-03
    Description: We describe the development and application of methods for high-throughput neuroanatomy in Drosophila using light microscopy. These tools enable efficient multicolor stochastic labeling of neurons at both low and high densities. Expression of multiple membrane-targeted and distinct epitope-tagged proteins is controlled both by a transcriptional driver and by stochastic, recombinase-mediated...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 6
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    From The Cover: An isoform-specific allele of Drosophila N-cadherin disrupts a late step of R7 targeting (2005)
    National Academy of Sciences
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    Publication Date: 2005-08-25
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 7
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    Robo-3-mediated repulsive interactions guide R8 axons during Drosophila visual system development (2011)
    National Academy of Sciences
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    Publication Date: 2011-04-13
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 8
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    Robo-3-mediated repulsive interactions guide R8 axons during Drosophila visual system development [Neuroscience] (2011)
    National Academy of Sciences
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    Publication Date: 2011-05-04
    Description: The formation of neuronal connections requires the precise guidance of developing axons toward their targets. In the Drosophila visual system, photoreceptor neurons (R cells) project from the eye into the brain. These cells are grouped into some 750 clusters comprised of eight photoreceptors or R cells each. R cells fall into three classes: R1 to R6, R7, and R8. Posterior R8 cells are the first to project axons into the brain. How these axons select a specific pathway is not known. Here, we used a microarray-based approach to identify genes expressed in R8 neurons as they extend into the brain. We found that Roundabout-3 (Robo3), an axon-guidance receptor, is expressed specifically and transiently in R8 growth cones. In wild-type animals, posterior-most R8 axons extend along a border of glial cells demarcated by the expression of Slit, the secreted ligand of Robo3. In contrast, robo3 mutant R8 axons extend across this border and fasciculate inappropriately with other axon tracts. We demonstrate that either Robo1 or Robo2 rescues the robo3 mutant phenotype when each is knocked into the endogenous robo3 locus separately, indicating that R8 does not require a function unique to the Robo3 paralog. However, persistent expression of Robo3 in R8 disrupts the layer-specific targeting of R8 growth cones. Thus, the transient cell-specific expression of Robo3 plays a crucial role in establishing neural circuits in the Drosophila visual system by selectively regulating pathway choice for posterior-most R8 growth cones.
    Print ISSN: 0027-8424
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    Topics: Biology , Medicine , Natural Sciences in General
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  • 9
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    Multiple new site-specific recombinases for use in manipulating animal genomes [Genetics] (2011)
    National Academy of Sciences
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    Publication Date: 2011-08-24
    Description: Site-specific recombinases have been used for two decades to manipulate the structure of animal genomes in highly predictable ways and have become major research tools. However, the small number of recombinases demonstrated to have distinct specificities, low toxicity, and sufficient activity to drive reactions to completion in animals has been a limitation. In this report we show that four recombinases derived from yeast—KD, B2, B3, and R—are highly active and nontoxic in Drosophila and that KD, B2, B3, and the widely used FLP recombinase have distinct target specificities. We also show that the KD and B3 recombinases are active in mice.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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