title: The Toll/NF-κB signaling pathway is required for epidermal wound repair in Drosophila.
abstract: 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 actin-cable 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.
authors.affiliation: Instituto de Medicina Molecular, Edifício Egas Moniz, 1649-028 Lisbon, Portugal; and Centro de Estudos de Doenças Crónicas, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisbon, Portugal.
authors.forename: Lara
authors.initials: L
authors.lastname: Carvalho
authors.affiliation: Instituto de Medicina Molecular, Edifício Egas Moniz, 1649-028 Lisbon, Portugal; and Centro de Estudos de Doenças Crónicas, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisbon, Portugal.
authors.forename: António
authors.identifier: http://orcid.org/0000-0002-4193-6089
authors.initials: A
authors.lastname: Jacinto
authors.affiliation: Instituto de Medicina Molecular, Edifício Egas Moniz, 1649-028 Lisbon, Portugal; and nina.matova@aya.yale.edu.
authors.forename: Nina
authors.identifier: http://orcid.org/0000-0001-9074-7017
authors.initials: N
authors.lastname: Matova
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology*; D004625:Embryo, Nonmammalian / Q000502:physiology; D004817:Epidermis / Q000502:physiology*; D005453:Fluorescence; D036681:Fluorescence Recovery After Photobleaching; D007150:Immunohistochemistry; D016328:NF-kappa B / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D051193:Toll-Like Receptors / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology*
chemical_list: D015820:Cadherins; D029721:Drosophila Proteins; D016328:NF-kappa B; C068721:Tl protein, Drosophila; D051193:Toll-Like Receptors
keywords: Drosophila; E-cadherin; NF-κB transcription factors; Toll pathway; epithelial wound repair