<i>Drosophila</i>Rel proteins are central regulators of a robust, multi-organ immune network

Matova, Nina; Anderson, Kathryn V.

doi:10.1242/jcs.060731

Cited by 19 publications

(23 citation statements)

References 36 publications

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“…The Toll/NF-κB pathway responds to another type of intense stress caused by microbial infection, and both Drosophila larvae and adults rely on the pathway for immune protection (7,8,38,39). If the aim of immune defense is microbial clearance, then the animal likely employs a different set of NF-κB targets than the ones used in wound closure.…”

Section: Wound Repair Features Two Levels Of E-cadherin Regulation Bothmentioning

confidence: 99%

“…However, the interplay between transcription and the cytoskeletal structures that execute wound closure has not been investigated. Previously, we showed that two Drosophila NF-κB transcription factors, Dif and Dorsal, are required for the integrity of the larval epidermis (7). Although single Dif or dl mutants do not have a detectable epidermal phenotype, Dif dl double-mutant larvae have spontaneous epidermal lesions and systemic infection by microbes from the environment (8).…”

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confidence: 99%

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The Toll/NF-κB signaling pathway is required for epidermal wound repair in Drosophila

Carvalho

Jacinto

Matova

2014

Proc. Natl. Acad. Sci. U.S.A.

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The Toll/NF-κB pathway, first identified in studies of dorsal-ventral polarity in the early Drosophila embryo, is well known for its role in the innate immune response. Here, we reveal that the Toll/NF-κB pathway is essential for wound closure in late Drosophila embryos. Toll mutants and Dif dorsal (NF-κB) double mutants are unable to repair epidermal gaps. Dorsal is activated on wounding, and Dif and Dorsal are required for the sustained down-regulation of E-cadherin, an obligatory component of the adherens junctions (AJs), at the wound edge. This remodeling of the AJs promotes the assembly of an actin-myosin cable at the wound margin; contraction of the actin cable, in turn, closes the wound. In the absence of Toll or Dif and dorsal (dl), both E-cadherin down-regulation and actincable formation fail, thus resulting in open epidermal gaps. Given the conservation of the Toll/NF-κB pathway in mammals and the epithelial expression of many components of the pathway, this function in wound healing is likely to be conserved in vertebrates.Toll pathway | NF-κB transcription factors | epithelial wound repair |

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Section: Wound Repair Features Two Levels Of E-cadherin Regulation Bothmentioning

confidence: 99%

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confidence: 99%

The Toll/NF-κB signaling pathway is required for epidermal wound repair in Drosophila

Carvalho

Jacinto

Matova

2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Rapidly thereafter, Relish was linked to Gram-negative response through the IMD signaling pathway (Hedengren et al 1999), while Toll-mediated humoral responses were shown to be DIF and/or Dorsal dependent (Ip et al 1993; Manfruelli et al 1999; Meng et al 1999; Rutschmann et al 2000a, b). In larvae, DIF and Dorsal function in a redundant fashion to control AMP gene expression (humoral immunity) and promote blood cell survival (cellular immunity) (Ip et al 1993; Manfruelli et al 1999; Matova and Anderson 2006, 2010). However, in adults, humoral responses are primarily controlled by DIF (Rutschmann et al 2000a, b).…”

Section: Nf-κb Proteinsmentioning

confidence: 99%

NF-κB/Rel Proteins and the Humoral Immune Responses of Drosophila melanogaster

Ganesan

Aggarwal

Paquette

et al. 2010

Current Topics in Microbiology and Immunology

144

169

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Nuclear Factor-κB (NF-κB)/Rel transcription factors form an integral part of innate immune defenses and are conserved throughout the animal kingdom. Studying the function, mechanism of activation and regulation of these factors is crucial for understanding host responses to microbial infections. The fruit fly Drosophila melanogaster has proved to be a valuable model system to study these evolutionarily conserved NF-κB mediated immune responses. Drosophila combats pathogens through humoral and cellular immune responses. These humoral responses are well characterized and are marked by the robust production of a battery of anti-microbial peptides. Two NF-κB signaling pathways, the Toll and the IMD pathways, are responsible for the induction of these antimicrobial peptides. Signal transduction in these pathways is strikingly similar to that in mammalian TLR pathways. In this chapter, we discuss in detail the molecular mechanisms of microbial recognition, signal transduction and NF-κB regulation, in both the Toll and the IMD pathways. Similarities and differences relative to their mammalian counterparts are discussed, and recent advances in our understanding of the intricate regulatory networks in these NF-κB signaling pathways are also highlighted.

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“…Dorsal and Dif are required in larval epidermal cells to prevent melanized lesions from forming at random locations in the cuticle, suggesting that the dorsal and Dif genes are required for normal differentiation of an epidermal barrier, and/or for the normal repair of sporadic wounds that arise in the larval cuticle (18). In the Drosophila embryonic epidermis, Toll, Dif, and dorsal were also found necessary for the cytoskeletal processes that led to sealing of epidermis after laser wounding in late stage embryos (19).…”

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confidence: 99%

Toll pathway is required for wound-induced expression of barrier repair genes in the Drosophila epidermis

Capilla

Karachentsev

Patterson

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The epidermis serves as a protective barrier in animals. After epidermal injury, barrier repair requires activation of many wound response genes in epidermal cells surrounding wound sites. Two such genes in Drosophila encode the enzymes dopa decarboxylase (Ddc) and tyrosine hydroxylase (ple). In this paper we explore the involvement of the Toll/NF-κB pathway in the localized activation of wound repair genes around epidermal breaks. Robust activation of wound-induced transcription from ple and Ddc requires Toll pathway components ranging from the extracellular ligand Spätzle to the Dif transcription factor. Epistasis experiments indicate a requirement for Spätzle ligand downstream of hydrogen peroxide and protease function, both of which are known activators of wound-induced transcription. The localized activation of Toll a few cell diameters from wound edges is reminiscent of local activation of Toll in early embryonic ventral hypoderm, consistent with the hypothesis that the dorsal–ventral patterning function of Toll arose from the evolutionary cooption of a morphogen-responsive function in wound repair. Furthermore, the combinatorial activity of Toll and other signaling pathways in activating epidermal barrier repair genes can help explain why developmental activation of the Toll, ERK, or JNK pathways alone fail to activate wound repair loci.

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DrosophilaRel proteins are central regulators of a robust, multi-organ immune network

Cited by 19 publications

References 36 publications

The Toll/NF-κB signaling pathway is required for epidermal wound repair in Drosophila

The Toll/NF-κB signaling pathway is required for epidermal wound repair in Drosophila

NF-κB/Rel Proteins and the Humoral Immune Responses of Drosophila melanogaster

Toll pathway is required for wound-induced expression of barrier repair genes in the Drosophila epidermis

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