All organisms have developed mechanisms to respond to organ or tissue damage that may appear during development or during the adult life. This process of regeneration is a major long-standing problem in Developmental Biology. We are using the Drosophila melanogaster wing imaginal disc to study the response to major damage inflicted during development. Using the Gal4/UAS/Gal80TS conditional system, we have induced massive cell killing by forcing activity of the pro-apoptotic gene hid in two major regions of the disc as defined by Gal4 inserts in the genes rotund (rn) and spalt (sal). The procedure ensures that at the end of a 40–48 hrs of ablation period the great majority of the cells of the original Rn or Sal domains have been eliminated. The results indicate that the damage provokes an immediate response aimed to keep the integrity of the epithelium and to repair the region under ablation. This includes an increase in cell proliferation to compensate for the cell loss and the replacement of the dead cells by others from outside of the damaged area. The response is almost contemporaneous with the damage, so that at the end of the ablation period the targeted region is already reconstructed. We find that the proliferative response is largely systemic, as the number of cells in division increases all over the disc. Furthermore, our results indicate that the Dpp and Wg pathways are not specifically involved in the regenerative response, but that activity of the JNK pathway is necessary both inside and outside the ablated domain for its reconstruction.
Vyšlo v časopise: Tissue Homeostasis in the Wing Disc of : Immediate Response to Massive Damage during Development. PLoS Genet 9(4): e32767. doi:10.1371/journal.pgen.1003446 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003446
1. MorganTH (1901) Regeneration and Liability to Injury. Science 14 : 235–248.
2. CohenSM (1993) Imaginal disc development. The Development of Drosophila melanogaster Cold Spring Harbor Laboratory Press Volume II: 747–841.
3. Hadorn E (1978) Imaginal discs: transdetermination. Ashburner M, Wright TRF, editors The Genetics and Biology of Drosophila 2c Academic Press; New York: 555–617.
4. AffolterM, BaslerK (2007) The Decapentaplegic morphogen gradient: from pattern formation to growth regulation. Nat Rev Genet 8 : 663–674.
5. MartinFA, HerreraSC, MorataG (2009) Cell competition, growth and size control in the Drosophila wing imaginal disc. Development 136 : 3747–3756.
6. BryantPJ (1975) Pattern formation in the imaginal wing disc of Drosophila melanogaster: fate map, regeneration and duplication. J Exp Zool 193 : 49–77.
7. CallejaM, HerranzH, EstellaC, CasalJ, LawrenceP, et al. (2000) Generation of medial and lateral dorsal body domains by the pannier gene of Drosophila. Development 127 : 3971–3980.
8. TabataT, TakeiY (2004) Morphogens, their identification and regulation. Development 131 : 703–712.
9. HaynieJL, BryantPJ (1976) Intercalary regeneration in imaginal wing disk of Drosophila melanogaster. Nature 259 : 659–662.
10. McClureKD, SustarA, SchubigerG (2008) Three genes control the timing, the site and the size of blastema formation in Drosophila. Dev Biol 319 : 68–77.
11. SchubigerM, SustarA, SchubigerG (2010) Regeneration and transdetermination: the role of wingless and its regulation. Dev Biol 347 : 315–324.
12. CheraS, GhilaL, DobretzK, WengerY, BauerC, et al. (2009) Apoptotic cells provide an unexpected source of Wnt3 signaling to drive hydra head regeneration. Dev Cell 17 : 279–289.
13. Stoick-CooperCL, WeidingerG, RiehleKJ, HubbertC, MajorMB, et al. (2007) Distinct Wnt signaling pathways have opposing roles in appendage regeneration. Development 134 : 479–489.
14. Smith-BoltonRK, WorleyMI, KandaH, HariharanIK (2009) Regenerative growth in Drosophila imaginal discs is regulated by Wingless and Myc. Dev Cell 16 : 797–809.
15. BergantinosC, CorominasM, SerrasF (2010) Cell death-induced regeneration in wing imaginal discs requires JNK signalling. Development 137 : 1169–1179.
16. SunG, IrvineKD (2011) Regulation of Hippo signaling by Jun kinase signaling during compensatory cell proliferation and regeneration, and in neoplastic tumors. Developmental biology 350 : 139–151.
17. GruscheFA, DegoutinJL, RichardsonHE, HarveyKF (2011) The Salvador/Warts/Hippo pathway controls regenerative tissue growth in Drosophila melanogaster. Developmental biology 350 : 255–266.
18. Perez-GarijoA, ShlevkovE, MorataG (2009) The role of Dpp and Wg in compensatory proliferation and in the formation of hyperplastic overgrowths caused by apoptotic cells in the Drosophila wing disc. Development 136 : 1169–1177.
19. St PierreSE, GalindoMI, CousoJP, ThorS (2002) Control of Drosophila imaginal disc development by rotund and roughened eye: differentially expressed transcripts of the same gene encoding functionally distinct zinc finger proteins. Development 129 : 1273–1281.
20. BarrioR, de CelisJF (2004) Regulation of spalt expression in the Drosophila wing blade in response to the Decapentaplegic signaling pathway. Proc Natl Acad Sci U S A 101 : 6021–6026.
21. AgnelM, RoderL, VolaC, Griffin-SheaR (1992) A Drosophila rotund transcript expressed during spermatogenesis and imaginal disc morphogenesis encodes a protein which is similar to human Rac GTPase-activating (racGAP) proteins. Mol Cell Biol 12 : 5111–5122.
22. NgM, Diaz-BenjumeaFJ, CohenSM (1995) Nubbin encodes a POU-domain protein required for proximal-distal patterning in the Drosophila wing. Development 121 : 589–599.
23. PotterCJ, TasicB, RusslerEV, LiangL, LuoL (2010) The Q system: a repressible binary system for transgene expression, lineage tracing, and mosaic analysis. Cell 141 : 536–548.
24. AbbottLC, KarpenGH, SchubigerG (1981) Compartmental restrictions and blastema formation during pattern regulation in Drosophila imaginal leg discs. Dev Biol 87 : 64–75.
25. O'BrochtaDA, BryantPJ (1987) Distribution of S-phase cells during the regeneration of Drosophila imaginal wing discs. Dev Biol 119 : 137–142.
26. BurkeR, BaslerK (1996) Dpp receptors are autonomously required for cell proliferation in the entire developing Drosophila wing. Development 122 : 2261–2269.
27. Martin-CastellanosC, EdgarBA (2002) A characterization of the effects of Dpp signaling on cell growth and proliferation in the Drosophila wing. Development 129 : 1003–1013.
28. MartinFA, Perez-GarijoA, MorenoE, MorataG (2004) The brinker gradient controls wing growth in Drosophila. Development 131 : 4921–4930.
29. IgakiT, KandaH, Yamamoto-GotoY, KanukaH, KuranagaE, et al. (2002) Eiger, a TNF superfamily ligand that triggers the Drosophila JNK pathway. EMBO J 21 : 3009–3018.
30. MorenoE, YanM, BaslerK (2002) Evolution of TNF signaling mechanisms: JNK-dependent apoptosis triggered by Eiger, the Drosophila homolog of the TNF superfamily. Curr Biol 12 : 1263–1268.
31. Martin-BlancoE, GampelA, RingJ, VirdeeK, KirovN, et al. (1998) puckered encodes a phosphatase that mediates a feedback loop regulating JNK activity during dorsal closure in Drosophila. Genes Dev 12 : 557–570.
32. KimJ, SebringA, EschJJ, KrausME, VorwerkK, et al. (1996) Integration of positional signals and regulation of wing formation and identity by Drosophila vestigial gene. Nature 382 : 133–138.
33. WhitworthAJ, RussellS (2003) Temporally dynamic response to Wingless directs the sequential elaboration of the proximodistal axis of the Drosophila wing. Dev Biol 254 : 277–288.
34. Morata G, Herrera SC (2010) Differential division rates and size control in the wing disc. Fly (Austin) 4.
35. LinG, SlackJM (2008) Requirement for Wnt and FGF signaling in Xenopus tadpole tail regeneration. Developmental biology 316 : 323–335.
36. JacintoA, WoolnerS, MartinP (2002) Dynamic analysis of dorsal closure in Drosophila: from genetics to cell biology. Dev Cell 3 : 9–19.
37. Pastor-ParejaJC, GraweF, Martin-BlancoE, Garcia-BellidoA (2004) Invasive cell behavior during Drosophila imaginal disc eversion is mediated by the JNK signaling cascade. Dev Cell 7 : 387–399.
38. McGuireSE, LePT, OsbornAJ, MatsumotoK, DavisRL (2003) Spatiotemporal rescue of memory dysfunction in Drosophila. Science 302 : 1765–1768.
39. HaleyB, HendrixD, TrangV, LevineM (2008) A simplified miRNA-based gene silencing method for Drosophila melanogaster. Dev Biol 321 : 482–490.
40. StruhlG, BaslerK (1993) Organizing activity of wingless protein in Drosophila. Cell 72 : 527–540.
41. EvansCJ, OlsonJM, NgoKT, KimE, LeeNE, et al. (2009) G-TRACE: rapid Gal4-based cell lineage analysis in Drosophila. Nat Methods 6 : 603–605.
42. LeulierF, RibeiroPS, PalmerE, TenevT, TakahashiK, et al. (2006) Systematic in vivo RNAi analysis of putative components of the Drosophila cell death machinery. Cell Death Differ 13 : 1663–1674.
43. MarksteinM, PitsouliC, VillaltaC, CelnikerSE, PerrimonN (2008) Exploiting position effects and the gypsy retrovirus insulator to engineer precisely expressed transgenes. Nat Genet 40 : 476–483.
44. GrothAC, FishM, NusseR, CalosMP (2004) Construction of transgenic Drosophila by using the site-specific integrase from phage phiC31. Genetics 166 : 1775–1782.
45. ShlevkovE, MorataG (2012) A dp53/JNK-dependant feedback amplification loop is essential for the apoptotic response to stress in Drosophila. Cell Death Differ 19 : 451–460.
46. WilliamsJA, BellJB, CarrollSB (1991) Control of Drosophila wing and haltere development by the nuclear vestigial gene product. Genes Dev 5 : 2481–2495.
47. DuncanDM, BurgessEA, DuncanI (1998) Control of distal antennal identity and tarsal development in Drosophila by spineless-aristapedia, a homolog of the mammalian dioxin receptor. Genes Dev 12 : 1290–1303.
48. MartinFA, MorataG (2006) Compartments and the control of growth in the Drosophila wing imaginal disc. Development 133 : 4421–4426.
49. BusturiaA, MorataG (1988) Ectopic expression of homeotic genes caused by the elimination of the Polycomb gene in Drosophila imaginal epidermis. Development 104 : 713–720.
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