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6 Janelia Publications

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    07/02/18 | Apical and basal matrix remodeling control epithelial morphogenesis.
    Diaz-de-la-Loza M, Ray RP, Ganguly PS, Alt S, Davis JR, Hoppe A, Tapon N, Salbreux G, Thompson BJ
    Developmental Cell. 2018 Jul 02;46(1):23-39.e5. doi: 10.1016/j.devcel.2018.06.006

    Epithelial tissues can elongate in two dimensions by polarized cell intercalation, oriented cell division, or cell shape change, owing to local or global actomyosin contractile forces acting in the plane of the tissue. In addition, epithelia can undergo morphogenetic change in three dimensions. We show that elongation of the wings and legs of Drosophila involves a columnar-to-cuboidal cell shape change that reduces cell height and expands cell width. Remodeling of the apical extracellular matrix by the Stubble protease and basal matrix by MMP1/2 proteases induces wing and leg elongation. Matrix remodeling does not occur in the haltere, a limb that fails to elongate. Limb elongation is made anisotropic by planar polarized Myosin-II, which drives convergent extension along the proximal-distal axis. Subsequently, Myosin-II relocalizes to lateral membranes to accelerate columnar-to-cuboidal transition and isotropic tissue expansion. Thus, matrix remodeling induces dynamic changes in actomyosin contractility to drive epithelial morphogenesis in three dimensions.

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    04/09/18 | Odorant binding protein 69a connects social interaction to modulation of social responsiveness in Drosophila.
    Bentzur A, Shmueli A, Omesi L, Ryvkin J, Knapp J, Parnas M, Davis FP, Shohat-Ophir G
    PLoS Genetics. 2018 Apr 09;14(4):e1007328. doi: 10.1371/journal.pgen.1007328

    Living in a social environment requires the ability to respond to specific social stimuli and to incorporate information obtained from prior interactions into future ones. One of the mechanisms that facilitates social interaction is pheromone-based communication. In Drosophila melanogaster, the male-specific pheromone cis-vaccenyl acetate (cVA) elicits different responses in male and female flies, and functions to modulate behavior in a context and experience-dependent manner. Although it is the most studied pheromone in flies, the mechanisms that determine the complexity of the response, its intensity and final output with respect to social context, sex and prior interaction, are still not well understood. Here we explored the functional link between social interaction and pheromone-based communication and discovered an odorant binding protein that links social interaction to sex specific changes in cVA related responses. Odorant binding protein 69a (Obp69a) is expressed in auxiliary cells and secreted into the olfactory sensilla. Its expression is inversely regulated in male and female flies by social interactions: cVA exposure reduces its levels in male flies and increases its levels in female flies. Increasing or decreasing Obp69a levels by genetic means establishes a functional link between Obp69a levels and the extent of male aggression and female receptivity. We show that activation of cVA-sensing neurons is sufficeint to regulate Obp69a levels in the absence of cVA, and requires active neurotransmission between the sensory neuron to the second order olfactory neuron. The cross-talk between sensory neurons and non-neuronal auxiliary cells at the olfactory sensilla, represents an additional component in the machinery that promotes behavioral plasticity to the same sensory stimuli in male and female flies.

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    12/31/17 | A topographic axis of transcriptional identity in thalamus.
    Phillips JW, Schulman A, Hara E, Liu C, Shields BC, Korff W, Lemire A, Dudman JT, Nelson SB, Hantman AW
    bioRxiv. 2017 Dec 31:241315. doi: 10.1101/241315

    A fundamental goal in neuroscience is to uncover common principles by which different modalities of information are processed. In the mammalian brain, thalamus acts as the essential hub for forebrain circuits handling inputs from sensory, motor, limbic, and cognitive pathways. Whether thalamus imposes common transformations on each of these modalities is unknown. Molecular characterization offers a principled approach to revealing the organization of thalamus. Using near-comprehensive and projection-specific transcriptomic sequencing, we found that almost all thalamic nuclei fit into one of three profiles. These profiles lie on a single axis of genetic variance which is aligned with the mediolateral spatial axis of thalamus. Genes defining this axis of variance include receptors and ion channels, providing a systematic diversification of input/output transformations across the topography of thalamus. Single cell transcriptional profiling revealed graded heterogeneity within individual thalamic nuclei, demonstrating that a spectrum of cell types and potentially diverse input/output transforms exist within a given thalamic nucleus. Together, our data argue for an archetypal organization of pathways serving diverse input modalities, and provides a comprehensive organizational scheme for thalamus.

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    03/09/17 | Genetic and transgenic reagents for Drosophila simulans, D. mauritiana, D. yakuba, D. santomea and D. virilis.
    Stern DL, Crocker J, Ding Y, Frankel N, Kappes G, Kim E, Kuzmickas R, Lemire A, Mast JD, Picard S
    G3 (Bethesda, Md.). 2017 Mar 09;7(4):1339-47. doi: 10.1534/g3.116.038885

    Species of the Drosophila melanogaster species subgroup, including the species D. simulans, D. mauritiana, D. yakuba, and D. santomea, have long served as model systems for studying evolution. Studies in these species have been limited, however, by a paucity of genetic and transgenic reagents. Here we describe a collection of transgenic and genetic strains generated to facilitate genetic studies within and between these species. We have generated many strains of each species containing mapped piggyBac transposons including an enhanced yellow fluorescent protein gene expressed in the eyes and a phiC31 attP site-specific integration site. We have tested a subset of these lines for integration efficiency and reporter gene expression levels. We have also generated a smaller collection of other lines expressing other genetically encoded fluorescent molecules in the eyes and a number of other transgenic reagents that will be useful for functional studies in these species. In addition, we have mapped the insertion locations of 58 transposable elements in D. virilis that will be useful for genetic mapping studies.

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    11/16/16 | The genome of the crustacean Parhyale hawaiensis: a model for animal development, regeneration, immunity and lignocellulose digestion.
    Kao D, Lai AG, Stamataki E, Rosic S, Konstantinides N, Jarvis E, Di Donfrancesco A, Pouchkina-Stantcheva N, Semon M, Grillo M, Bruce H, Kumar S, Siwanowicz I, Le A, Lemire A, Extavour C, Browne W, Wolff C, Averof M, et al
    eLife. 2016 Nov 16;5:e20062. doi: 10.7554/eLife.20062

    Parhyale hawaiensis is a blossoming model system for studies of developmental mechanisms and more recently adult regeneration. We have sequenced the genome allowing annotation of all key signaling pathways, small non-coding RNAs and transcription factors that will enhance ongoing functional studies. Parhayle is a member of the Malacostraca, which includes crustacean food crop species. We analysed the immunity related genes of Parhyale as an important comparative system for these species, where immunity related aquaculture problems have increased as farming has intensified. We also find that Parhyale and other species within Multicrustacea contain the enzyme sets necessary to perform lignocellulose digestion (wood eating), suggesting this ability may predate the diversification of this lineage. Our data provide an essential resource for further development of the Parhyale model. The first Malacostracan genome sequence will underpin ongoing comparative work in important food crop species and research investigating lignocellulose as energy source.

    Publication first appeared in BioRxiv on August 2, 2016. http://dx.doi.org/10.1101/065789

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    04/26/16 | Hipposeq: a comprehensive RNA-seq database of gene expression in hippocampal principal neurons.
    Cembrowski MS, Wang L, Sugino K, Shields BC, Spruston N
    eLife. 2016;5:. doi: 10.7554/eLife.14997

    Clarifying gene expression in narrowly defined neuronal populations can provide insight into cellular identity, computation, and functionality. Here, we used next-generation RNA sequencing (RNA-seq) to produce a quantitative, whole genome characterization of gene expression for the major excitatory neuronal classes of the hippocampus; namely, granule cells and mossy cells of the dentate gyrus, and pyramidal cells of areas CA3, CA2, and CA1. Moreover, for the canonical cell classes of the trisynaptic loop, we profiled transcriptomes at both dorsal and ventral poles, producing a cell-class- and region-specific transcriptional description for these populations. This dataset clarifies the transcriptional properties and identities of lesser-known cell classes, and moreover reveals unexpected variation in the trisynaptic loop across the dorsal-ventral axis. We have created a public resource, Hipposeq (http://hipposeq.janelia.org), which provides analysis and visualization of these data and will act as a roadmap relating molecules to cells, circuits, and computation in the hippocampus.

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