title: Toll pathway is required for wound-induced expression of barrier repair genes in theDrosophilaepidermis.
abstract: 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 inDrosophilaencode 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 frompleandDdcrequires 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.
authors.affiliation: Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093.
authors.forename: Amalia
authors.initials: A
authors.lastname: Capilla
authors.affiliation: Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Karachentsev
authors.affiliation: Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Patterson
authors.affiliation: Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093.
authors.forename: Anita
authors.initials: A
authors.lastname: Hermann
authors.affiliation: Sophie Davis School Program of Biomedical Education, City University of New York School of Medicine, City College of New York, New York, NY 10031.
authors.forename: Michelle T
authors.initials: MT
authors.lastname: Juarez
authors.affiliation: Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093; billmcginnis.ucsd@gmail.com.
authors.forename: William
authors.initials: W
authors.lastname: McGinnis
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster / Q000378:metabolism*; D005786:Gene Expression Regulation; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014945:Wound Healing / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D016328:NF-kappa B; D051193:Toll-Like Receptors
keywords: Drosophila; NF-κB; Spätzle; epidermal Toll; wound repair