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5 Janelia Publications

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    10/01/11 | Anisotropic path searching for automatic neuron reconstruction.
    Xie J, Zhao T, Lee T, Myers E, Peng H
    Medical Image Analysis. 2011 Oct;15:680-9. doi: 10.1016/j.media.2011.05.013

    Full reconstruction of neuron morphology is of fundamental interest for the analysis and understanding of their functioning. We have developed a novel method capable of automatically tracing neurons in three-dimensional microscopy data. In contrast to template-based methods, the proposed approach makes no assumptions about the shape or appearance of neurite structure. Instead, an efficient seeding approach is applied to capture complex neuronal structures and the tracing problem is solved by computing the optimal reconstruction with a weighted graph. The optimality is determined by the cost function designed for the path between each pair of seeds and by topological constraints defining the component interrelations and completeness. In addition, an automated neuron comparison method is introduced for performance evaluation and structure analysis. The proposed algorithm is computationally efficient and has been validated using different types of microscopy data sets including Drosophila’s projection neurons and fly neurons with presynaptic sites. In all cases, the approach yielded promising results.

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    09/01/11 | New tools for the analysis of glial cell biology in Drosophila.
    Awasaki T, Lee T
    Glia. 2011 Sep;59(9):1377-86. doi: 10.1002/glia.21133

    Because of its genetic, molecular, and behavioral tractability, Drosophila has emerged as a powerful model system for studying molecular and cellular mechanisms underlying the development and function of nervous systems. The Drosophila nervous system has fewer neurons and exhibits a lower glia:neuron ratio than is seen in vertebrate nervous systems. Despite the simplicity of the Drosophila nervous system, glial organization in flies is as sophisticated as it is in vertebrates. Furthermore, fly glial cells play vital roles in neural development and behavior. In addition, powerful genetic tools are continuously being created to explore cell function in vivo. In taking advantage of these features, the fly nervous system serves as an excellent model system to study general aspects of glial cell development and function in vivo. In this article, we review and discuss advanced genetic tools that are potentially useful for understanding glial cell biology in Drosophila.

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    08/16/11 | Serotonin-mushroom body circuit modulating the formation of anesthesia-resistant memory in Drosophila.
    Lee P, Lin H, Chang Y, Fu T, Dubnau J, Hirsh J, Lee T, Chiang A
    Proceedings of the National Academy of Sciences of the United States of America. 2011 Aug 16;108(33):13794-9. doi: 10.1073/pnas.1019483108

    Pavlovian olfactory learning in Drosophila produces two genetically distinct forms of intermediate-term memories: anesthesia-sensitive memory, which requires the amnesiac gene, and anesthesia-resistant memory (ARM), which requires the radish gene. Here, we report that ARM is specifically enhanced or inhibited in flies with elevated or reduced serotonin (5HT) levels, respectively. The requirement for 5HT was additive with the memory defect of the amnesiac mutation but was occluded by the radish mutation. This result suggests that 5HT and Radish protein act on the same pathway for ARM formation. Three supporting lines of evidence indicate that ARM formation requires 5HT released from only two dorsal paired medial (DPM) neurons onto the mushroom bodies (MBs), the olfactory learning and memory center in Drosophila: (i) DPM neurons were 5HT-antibody immunopositive; (ii) temporal inhibition of 5HT synthesis or release from DPM neurons, but not from other serotonergic neurons, impaired ARM formation; (iii) knocking down the expression of d5HT1A serotonin receptors in α/β MB neurons, which are innervated by DPM neurons, inhibited ARM formation. Thus, in addition to the Amnesiac peptide required for anesthesia-sensitive memory formation, the two DPM neurons also release 5HT acting on MB neurons for ARM formation.

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    06/19/11 | Glia instruct developmental neuronal remodeling through TGF-β signaling.
    Awasaki T, Huang Y, O’Connor MB, Lee T
    Nature Neuroscience. 2011 Jun 19;14(7):821-3. doi: 10.1038/nn.2833

    We found that glia secrete myoglianin, a TGF-β ligand, to instruct developmental neural remodeling in Drosophila. Glial myoglianin upregulated neuronal expression of an ecdysone nuclear receptor that triggered neurite remodeling following the late-larval ecdysone peak. Thus glia orchestrate developmental neural remodeling not only by engulfment of unwanted neurites but also by enabling neuron remodeling.

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    12/27/10 | Orphan nuclear receptors control neuronal remodeling during fly metamorphosis.
    Tzumin Lee , Takeshi Awasaki
    Nature Neuroscience. 2010 Dec 27;14:6-7. doi: 10.1038/nn0111-6

    News & Views | Published: 27 December 2010

    Orphan nuclear receptors control neuronal remodeling during fly metamorphosis

    Nature Neuroscience volume 14, pages 6–7 (2011) | Download Citation

    Pruning of excess branches is essential for the maturation of developing neuronal circuits. Cross-talk between TGF-β signaling and two antagonistic orphan nuclear receptors governs the pruning of larval γ neurons in the Drosophila pupa.

    Neural circuits are remodeled as the brain matures or acquires new functions. Such developmental remodeling involves complex cellular changes that are tightly regulated in space and time. During metamorphosis of holometabolous insect brains, most larval functional neurons are rewired into the adult circuitry, and study of these processes has been particularly fruitful for the elucidation of the mechanisms that underlie neuron remodeling1. In metamorphosing Drosophila, nuclear signaling of the steroid hormone receptor ecdysone receptor B1 isoform (EcR-B1) cell-autonomously orchestrates neuron remodeling. Only neurons destined to remodel upregulate EcR-B1 expression before a crucial pre-pupal ecdysone pulse2. It is therefore necessary to determine the mechanisms that pattern EcR-B1 expression to understand how developmental neuronal remodeling is programmed in Drosophila.

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