To establish a genetic system to study postembryonic wound healing, we characterized epidermal healing in Drosophila larvae. Following puncture wounding, larvae begin bleed but within an hour plug forms the gap. Over next couple of hours outer part melanizes form scab, and cells surrounding orient toward it then fuse syncytium. Subsequently, more-peripheral with central During this time, Jun N-terminal kinase (JNK) pathway is activated gradient emanating out from wound, spread along or...

Aa robust inflammatory response to tissue damage and infection is conserved across almost all animal phyla. Neutrophils macrophages, or their equivalents, are drawn the wound site where they engulf cell matrix debris release signals that direct components of repair process. This orchestrated migration clinically important, yet, date, leukocyte chemotaxis has largely been studied in vitro. Here, we describe a genetically tractable vivo model inflammation Drosophila melanogaster embryo...

Insects have an open circulatory system in which the heart pumps blood (hemolymph) into body cavity, where it directly bathes internal organs and epidermis. The contains free tissue-bound immune cells that function inflammatory response. Here, we use live imaging of transgenic Drosophila larvae with fluorescently labeled (hemocytes) to investigate dynamics larval their response tissue injury. We find that, under normal conditions, rapidly circulate, whereas are sessile. After epidermal...

The axonal chemoattractant netrin-1 guides spinal commissural axons by activating its receptor DCC (Deleted in Colorectal Cancer). We have found that chemical inhibitors of metalloproteases potentiate netrin-mediated axon outgrowth vitro. also is a substrate for metalloprotease-dependent ectodomain shedding, and the block proteolytic processing cause an increase protein levels on within cord explants. Thus, potentiation netrin activity may result from stabilization axons, regulate migration...

Robust mechanisms for tissue repair are critical survival of multicellular organisms. Efficient cutaneous wound requires the migration cells at edge and farther back within epidermal sheet, but genes that control coordinate these migrations remain obscure. This is in part because a systematic screening approach vivo identification classification postembryonic closure has yet to be developed. Here, we performed proof-of-principle reporter-based RNAi screen Drosophila melanogaster larval...

Pain signaling in vertebrates is modulated by neuropeptides like Substance P (SP). To determine whether such modulation conserved and potentially uncover novel interactions between nociceptive pathways we examined SP/Tachykinin a Drosophila model of tissue damage-induced hypersensitivity. Tissue-specific knockdowns genetic mutant analyses revealed that both Tachykinin Tachykinin-like receptor (DTKR99D) are required for thermal sensitization. Electrophysiological recording showed DTKR99D...

Chemically induced nociception has not yet been studied intensively in genetically tractable models. Hence, our goal was to establish a Drosophila assay that can be used study the cellular and molecular/genetic bases of chemically nociception. larvae exposed increasing concentrations hydrochloric acid (HCl) produced an increasingly intense aversive rolling response. HCl (0.5%) subthreshold provoked no All classes peripheral multidendritic (md) sensory neurons (classes I–IV) are required for...

Summary Injury is an inevitable part of life, making wound healing essential for survival. In postembryonic skin, closure requires that epidermal cells recognize the presence a gap and change their behavior to migrate across it. Drosophila larvae, two signaling pathways [the Jun N-terminal kinase (JNK) pathway Pvr receptor tyrosine pathway] regulation actin cytoskeleton. this other systems, it remains unclear how initiate connect regulators help execute wound-induced cell migrations. Here,...

Nociceptive sensitization is a common feature in chronic pain, but its basic cellular mechanisms are only partially understood. The present study used the <i>Drosophila melanogaster</i> model system and candidate gene approach to identify novel components required for modulation of an injury-induced nociceptive pathway presumably downstream Hedgehog. This demonstrates that RNAi silencing member Bone Morphogenetic Protein (BMP) signaling pathway, Decapentaplegic (Dpp), specifically Class IV...

Mechanical sensitization is one of the most difficult clinical pain problems to treat. However, molecular and genetic bases mechanical nociception are unclear. Here we develop a <i>Drosophila</i> model investigate ion channels signaling pathways that regulate nociception. We fabricated von Frey filaments span subthreshold high noxious range for larvae. Using these, discovered pressure (force/area), rather than force per se, main determinant aversive rolling responses stimuli. demonstrated...

ABSTRACT Diabetes-associated nociceptive hypersensitivity affects diabetic patients with hard-to-treat chronic pain. Because multiple tissues are affected by systemic alterations in insulin signaling, the functional locus of signaling diabetes-associated remains obscure. Here, we used Drosophila nociception/nociceptive sensitization assays to investigate role Insulin receptor (Insulin-like receptor, InR) hypersensitivity. InR mutant larvae exhibited mostly normal baseline thermal nociception...

In this article, we demonstrate assays to study thermal nociception in Drosophila larvae. One assay involves spatially-restricted (local) stimulation of nociceptors1,2 while the second a wholesale (global) activation most or all such neurons3. Together, these techniques allow visualization and quantification behavioral functions nociceptive sensory neurons. The larva is an established model system nociception, response potentially harmful temperatures that evolutionarily conserved across...

Nociceptive sensitization involves an increase in responsiveness of pain sensing neurons to sensory stimuli, typically through the lowering their nociceptive threshold. is common following tissue damage, inflammation, and disease serves protect affected area while it heals. Organisms can become sensitized a range noxious innocuous including thermal stimuli. The basic mechanisms underlying warm or painfully hot stimuli have begun be elucidated, however, cold not well understood. Here, we...

Organismal lifespan has been the primary readout in aging research. However, how longevity genes control tissue-specific remains an open question. To examine crosstalk between programs and specific tissues during aging, biomarkers of organ-specific are urgently needed. Since earliest signs occur skin, we sought to skin a genetically tractable model. Here introduce Drosophila model aging. The epidermis undergoes dramatic morphological deterioration with age that includes membrane nuclear...

Abstract Tumor necrosis factor (TNF) signaling is required for inflammatory nociceptive (pain) sensitization in Drosophila and vertebrates. Nociceptive larvae following UV-induced tissue damage accompanied by epidermal apoptosis requires epidermal-derived TNF/Eiger the initiator caspase, Dronc. Major gaps remain regarding TNF function sensitization, including relationship between apoptosis/tissue production, downstream this context, target genes that modulate behaviors. Here, apoptotic cell...

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 molecular/genetic basis wound healing responses. The early studies this growing field focused on signature event healing--the closure epidermal gap through cell migration. These showed that there is conserved dichotomy between embryonic postembryonic repair processes flies vertebrates: wounds heal contraction supracellular actin pursestring assembled at...