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      Neurotransmitter identity is acquired in a lineage-restricted manner in the Drosophila CNS

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          Abstract

          The vast majority of the adult fly ventral nerve cord is composed of 34 hemilineages, which are clusters of lineally related neurons. Neurons in these hemilineages use one of the three fast-acting neurotransmitters (acetylcholine, GABA, or glutamate) for communication. We generated a comprehensive neurotransmitter usage map for the entire ventral nerve cord. We did not find any cases of neurons using more than one neurotransmitter, but found that the acetylcholine specific gene ChAT is transcribed in many glutamatergic and GABAergic neurons, but these transcripts typically do not leave the nucleus and are not translated. Importantly, our work uncovered a simple rule: All neurons within a hemilineage use the same neurotransmitter. Thus, neurotransmitter identity is acquired at the stem cell level. Our detailed transmitter- usage/lineage identity map will be a great resource for studying the developmental basis of behavior and deciphering how neuronal circuits function to regulate behavior.

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          Most cited references52

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          Plug-and-play genetic access to drosophila cell types using exchangeable exon cassettes.

          Genetically encoded effectors are important tools for probing cellular function in living animals, but improved methods for directing their expression to specific cell types are required. Here, we introduce a simple, versatile method for achieving cell-type-specific expression of transgenes that leverages the untapped potential of "coding introns" (i.e., introns between coding exons). Our method couples the expression of a transgene to that of a native gene expressed in the cells of interest using intronically inserted "plug-and-play" cassettes (called "Trojan exons") that carry a splice acceptor site followed by the coding sequences of T2A peptide and an effector transgene. We demonstrate the efficacy of this approach in Drosophila using lines containing suitable MiMIC (Minos-mediated integration cassette) transposons and a palette of Trojan exons capable of expressing a range of commonly used transcription factors. We also introduce an exchangeable, MiMIC-like Trojan exon construct that can be targeted to coding introns using the Crispr/Cas system.
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            Role of GABAergic inhibition in shaping odor-evoked spatiotemporal patterns in the Drosophila antennal lobe.

            Drosophila olfactory receptor neurons project to the antennal lobe, the insect analog of the mammalian olfactory bulb. GABAergic synaptic inhibition is thought to play a critical role in olfactory processing in the antennal lobe and olfactory bulb. However, the properties of GABAergic neurons and the cellular effects of GABA have not been described in Drosophila, an important model organism for olfaction research. We have used whole-cell patch-clamp recording, pharmacology, immunohistochemistry, and genetic markers to investigate how GABAergic inhibition affects olfactory processing in the Drosophila antennal lobe. We show that many axonless local neurons (LNs) in the adult antennal lobe are GABAergic. GABA hyperpolarizes antennal lobe projection neurons (PNs) via two distinct conductances, blocked by a GABAA- and GABAB-type antagonist, respectively. Whereas GABAA receptors shape PN odor responses during the early phase of odor responses, GABAB receptors mediate odor-evoked inhibition on longer time scales. The patterns of odor-evoked GABAB-mediated inhibition differ across glomeruli and across odors. Finally, we show that LNs display broad but diverse morphologies and odor preferences, suggesting a cellular basis for odor- and glomerulus-dependent patterns of inhibition. Together, these results are consistent with a model in which odors elicit stimulus-specific spatial patterns of GABA release, and as a result, GABAergic inhibition increases the degree of difference between the neural representations of different odors.
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              Topographic organization of embryonic motor neurons defined by expression of LIM homeobox genes.

              Motor neurons located at different positions in the embryonic spinal cord innervate distinct targets in the periphery, establishing a topographic neural map. The topographic organization of motor projections depends on the generation of subclasses of motor neurons that select specific paths to their targets. We have cloned a family of LIM homeobox genes in chick and show here that the combinatorial expression of four of these genes, Islet-1, Islet-2, Lim-1, and Lim-3, defines subclasses of motor neurons that segregate into columns in the spinal cord and select distinct axonal pathways. These genes are expressed prior to the formation of distinct motor axon pathways and before motor columns appear. Our results suggest that LIM homeobox genes contribute to the generation of motor neuron diversity and may confer subclasses of motor neurons with the ability to select specific axon pathways, thereby initiating the topographic organization of motor projections.
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                Author and article information

                Contributors
                Role: Reviewing Editor
                Role: Senior Editor
                Journal
                eLife
                Elife
                eLife
                eLife
                eLife Sciences Publications, Ltd
                2050-084X
                26 March 2019
                2019
                : 8
                : e43701
                Affiliations
                [1 ]deptJanelia Research Campus Howard Hughes Medical Institute AshburnUnited States
                [2 ]deptDepartment of Genetics Washington University Saint LouisUnited States
                [3 ]deptDepartment of Anatomy and Structural Biology Albert Einstein College of Medicine BronxUnited States
                [4 ]deptFriday Harbor Laboratories University of Washington Friday HarborUnited States
                National Centre for Biological Sciences, Tata Institute of Fundamental Research India
                National Centre for Biological Sciences, Tata Institute of Fundamental Research India
                National Centre for Biological Sciences, Tata Institute of Fundamental Research India
                University of Oregon United States
                University of Cambridge United Kingdom
                Author information
                http://orcid.org/0000-0003-2468-9618
                http://orcid.org/0000-0002-6725-0093
                http://orcid.org/0000-0002-9209-5435
                Article
                43701
                10.7554/eLife.43701
                6504232
                30912745
                3fb9b4c5-ed3e-4d08-8bfb-180fbb7ab711
                © 2019, Lacin et al

                This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

                History
                : 16 November 2018
                : 23 March 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000011, Howard Hughes Medical Institute;
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: NS083086
                Award Recipient :
                The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
                Categories
                Research Article
                Developmental Biology
                Neuroscience
                Custom metadata
                Lineally related neurons in the adult Drosophila ventral nerve cord use the same neurotransmitter to communicate with other neurons.

                Life sciences
                neurotransmitters,ventral nerve cord,stem cell,neuroblast,lineages,central nervous system,d. melanogaster

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