an-improved-method-for-accurate-rapid-measurement-flight-performance

An Improved Method for Accurate and Rapid Measurement of Flight Performance in <em>Drosophila</em>

Drosophila has proven to be a useful model system for analysis of behavior, including flight. The initial flight tester involved dropping flies into an ...

visualizing-synaptic-degeneration-adult-drosophila-association-with

Visualizing Synaptic Degeneration in Adult <em>Drosophila</em> in Association with Neurodegeneration

Drosophila serves as a useful model for assessing synaptic structure and function associated with neurodegenerative diseases. While much work has focused ...

University of Wisconsin-Madison

Lehigh University

Insects have an open circulatory system in which the heart pumps blood (hemolymph) into the body cavity, where it directly bathes the internal organs and epidermis. The blood contains free and tissue-bound immune cells that function in the inflammatory response. Here, we use live imaging of transgenic Drosophila larvae with fluorescently labeled blood cells (hemocytes) to investigate the circulatory dynamics of larval blood cells and their response to tissue injury. We find that, under normal conditions, the free cells rapidly circulate, whereas the tissue-bound cells are sessile. After epidermal wounding, tissue-bound cells around the wound site remain sessile and unresponsive, whereas circulating cells are rapidly recruited to the site of damage by adhesive capture. After capture, these cells distribute across the wound, appear phagocytically active, and are subsequently released back into circulation by the healing epidermis. The results demonstrate that circulating cells function as a surveillance system that monitors larval tissues for damage, and that adhesive capture, an important mechanism of recruitment of circulating cells to inflammatory sites in vertebrates, is shared by insects and vertebrates despite the vastly different architectures of their circulatory systems.

Circulating blood cells function as a surveillance system for damaged tissue in Drosophila larvae.

In the past few years a number of fly labs have studied wounded Drosophila embryos,(1-3) larvae(4-6) and adults7 in an effort to uncover the molecular/genetic basis of wound healing responses. The early studies in this growing field focused on the signature event of wound healing--the closure of the epidermal gap through cell migration. These studies showed that there is a conserved dichotomy between embryonic and postembryonic repair processes in flies and vertebrates: embryonic wounds heal through contraction of a supracellular actin pursestring assembled at the wound margin and postembryonic wounds heal through extension of cell processes and migration across the wound gap. Now, our group and others have begun to use these wounding assays to examine other steps of the healing process. Inflammation, the recruitment of hemocytes (blood cells) to the site of tissue damage, has been a particular focus of recent studies. This extra view article summarizes these recent findings on wound-induced inflammation, especially the curious dichotomy between modes of blood cell recruitment in embryos and larvae.

Active cop, passive cop: developmental stage-specific modes of wound-induced blood cell recruitment in Drosophila.

Heightened nociceptive (pain) sensitivity is an adaptive response to tissue damage and serves to protect the site of injury. Multiple mediators of nociceptive sensitization have been identified in vertebrates, but the complexity of the vertebrate nervous system and tissue-repair responses has hindered identification of the precise roles of these factors.

Cytokine signaling mediates UV-induced nociceptive sensitization in Drosophila larvae.

Nociceptive sensitization is a conserved form of neuronal plasticity that serves an important survival function, as it fosters behavior that protects damaged tissue during healing. This sensitization may involve a lowering of the nociceptive threshold (allodynia) or an increased response to normally noxious stimuli (hyperalgesia). Although nociceptive sensitization has been intensively studied in vertebrate models, an open question in the field is the extent to which allodynia and hyperalgesia, which almost always occur in tandem, are truly separate events at the mechanistic level. We recently introduced a genetically tractable model for damage-induced nociceptive sensitization in Drosophila larvae, and identified a conserved cytokine signaling module that mediates development of allodynia following UV irradiation. This pathway includes the Drosophila homolog of Tumor Necrosis Factor-alpha (TNFalpha), Eiger, which is released from damaged epidermal cells and acts directly on its receptor, Wengen, located on nociceptive sensory neurons. Here we show that although Eiger and Wengen are both required for the development of thermal allodynia, they are dispensable for thermal hyperalgesia, suggesting, contrary to what is commonly assumed, that these two forms of hypersensitivity are initiated by separate genetic pathways.

Two sides of the same coin no longer: genetic separation of nociceptive sensitization responses.

Nociceptive sensitization is a tissue damage response whereby sensory neurons near damaged tissue enhance their responsiveness to external stimuli. This sensitization manifests as allodynia (aversive withdrawal to previously nonnoxious stimuli) and/or hyperalgesia (exaggerated responsiveness to noxious stimuli). Although some factors mediating nociceptive sensitization are known, inadequacies of current analgesic drugs have prompted a search for additional targets.

Hedgehog signaling regulates nociceptive sensitization.

Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons, resulting in progressive locomotor dysfunction. Identification of genes required for the maintenance of these neurons should help to identify potential therapeutic targets. However, little is known regarding the factors that render dopaminergic neurons selectively vulnerable to PD. Here, we show that  mutants exhibit an age-dependent progressive loss of dopaminergic neurons, along with subsequent locomotor defects and a shortened lifespan. Knockdown of Scarlet specifically within dopaminergic neurons is sufficient to produce this neurodegeneration, demonstrating a unique role for Scarlet beyond its well-characterized role in eye pigmentation. Both genetic and pharmacological manipulation of the kynurenine pathway rescued loss of dopaminergic neurons by promoting synthesis of the free radical scavenger kynurenic acid (KYNA) and limiting the production of the free radical generator 3-hydroxykynurenine (3-HK). Finally, we show that expression of wild-type Scarlet is neuroprotective in a model of PD, suggesting that manipulating kynurenine metabolism may be a potential therapeutic option in treating PD.This article has an associated First Person interview with the first author of the paper.

Daniel T. Babcock

Department of Genetics

University of Wisconsin-Madison

An Improved Method for Accurate and Rapid Measurement of Flight Performance in Drosophila

Visualizing Synaptic Degeneration in Adult Drosophila in Association with Neurodegeneration