Remodelling of oxygen-transporting tracheoles drives intestinal regeneration and tumorigenesis in Drosophila.
Animals
Animals, Genetically Modified
/ metabolism
Cell Transformation, Neoplastic
/ metabolism
DNA-Binding Proteins
/ metabolism
Drosophila
/ metabolism
Drosophila Proteins
/ metabolism
Gene Expression Regulation, Developmental
/ physiology
Hypoxia
/ metabolism
Oxygen
/ metabolism
Receptors, Fibroblast Growth Factor
/ genetics
Regeneration
/ physiology
Journal
Nature cell biology
ISSN: 1476-4679
Titre abrégé: Nat Cell Biol
Pays: England
ID NLM: 100890575
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
21
04
2020
accepted:
31
03
2021
pubmed:
12
5
2021
medline:
21
7
2021
entrez:
11
5
2021
Statut:
ppublish
Résumé
The Drosophila trachea, as the functional equivalent of mammalian blood vessels, senses hypoxia and oxygenates the body. Here, we show that the adult intestinal tracheae are dynamic and respond to enteric infection, oxidative agents and tumours with increased terminal branching. Increased tracheation is necessary for efficient damage-induced intestinal stem cell (ISC)-mediated regeneration and is sufficient to drive ISC proliferation in undamaged intestines. Gut damage or tumours induce HIF-1α (Sima in Drosophila), which stimulates tracheole branching via the FGF (Branchless (Bnl))-FGFR (Breathless (Btl)) signalling cascade. Bnl-Btl signalling is required in the intestinal epithelium and the trachea for efficient damage-induced tracheal remodelling and ISC proliferation. Chemical or Pseudomonas-generated reactive oxygen species directly affect the trachea and are necessary for branching and intestinal regeneration. Similarly, tracheole branching and the resulting increase in oxygenation are essential for intestinal tumour growth. We have identified a mechanism of tracheal-intestinal tissue communication, whereby damage and tumours induce neo-tracheogenesis in Drosophila, a process reminiscent of cancer-induced neoangiogenesis in mammals.
Identifiants
pubmed: 33972730
doi: 10.1038/s41556-021-00674-1
pii: 10.1038/s41556-021-00674-1
pmc: PMC8567841
mid: NIHMS1742527
doi:
Substances chimiques
DNA-Binding Proteins
0
Drosophila Proteins
0
Receptors, Fibroblast Growth Factor
0
Oxygen
S88TT14065
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
497-510Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM124434
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM140900
Pays : United States
Commentaires et corrections
Type : CommentIn
Références
Ghabrial, A., Luschnig, S., Metzstein, M. M. & Krasnow, M. A. Branching morphogenesis of the Drosophila tracheal system. Annu. Rev. Cell Dev. Biol. 19, 623–647 (2003).
pubmed: 14570584
doi: 10.1146/annurev.cellbio.19.031403.160043
Hayashi, S. & Kondo, T. Development and function of the Drosophila tracheal system. Genetics 209, 367–380 (2018).
pubmed: 29844090
pmcid: 5972413
doi: 10.1534/genetics.117.300167
Jarecki, J., Johnson, E. & Krasnow, M. A. Oxygen regulation of airway branching in Drosophila is mediated by branchless FGF. Cell 99, 211–220 (1999).
pubmed: 10535739
doi: 10.1016/S0092-8674(00)81652-9
Centanin, L. et al. Cell autonomy of HIF effects in Drosophila: tracheal cells sense hypoxia and induce terminal branch sprouting. Dev. Cell 14, 547–558 (2008).
pubmed: 18410730
doi: 10.1016/j.devcel.2008.01.020
Best, B. T. Single-cell branching morphogenesis in the Drosophila trachea. Dev. Biol. 451, 5–15 (2019).
pubmed: 30529233
doi: 10.1016/j.ydbio.2018.12.001
Eilken, H. M. & Adams, R. H. Dynamics of endothelial cell behavior in sprouting angiogenesis. Curr. Opin. Cell Biol. 22, 617–625 (2010).
pubmed: 20817428
doi: 10.1016/j.ceb.2010.08.010
Fraisl, P., Mazzone, M., Schmidt, T. & Carmeliet, P. Regulation of angiogenesis by oxygen and metabolism. Dev. Cell 16, 167–179 (2009).
pubmed: 19217420
doi: 10.1016/j.devcel.2009.01.003
Apidianakis, Y., Tamamouna, V., Teloni, S. & Pitsouli, C. Chapter 5 - Intestinal stem cells: a decade of intensive research in Drosophila and the road ahead. Adv. Insect Physiol. (ed. Ligoxygakis, P.) vol. 52, 139–178 (Academic Press, Elsevier 2017).
Jiang, H., Tian, A. & Jiang, J. Intestinal stem cell response to injury: lessons from Drosophila. Cell Mol. Life Sci. 73, 3337–3349 (2016).
pubmed: 27137186
pmcid: 4998060
doi: 10.1007/s00018-016-2235-9
Lemaitre, B. & Miguel-Aliaga, I. The digestive tract of Drosophila melanogaster. Annu. Rev. Genet. 47, 377–404 (2013).
pubmed: 24016187
doi: 10.1146/annurev-genet-111212-133343
Jasper, H. Intestinal stem cell aging: origins and interventions. Annu. Rev. Physiol. 82, 203–226 (2020).
pubmed: 31610128
doi: 10.1146/annurev-physiol-021119-034359
Micchelli, C. A. & Perrimon, N. Evidence that stem cells reside in the adult Drosophila midgut epithelium. Nature 439, 475–479 (2006).
pubmed: 16340959
doi: 10.1038/nature04371
Ohlstein, B. & Spradling, A. The adult Drosophila posterior midgut is maintained by pluripotent stem cells. Nature 439, 470–474 (2006).
pubmed: 16340960
doi: 10.1038/nature04333
Zeng, X. & Hou, S. X. Enteroendocrine cells are generated from stem cells through a distinct progenitor in the adult Drosophila posterior midgut. Development 142, 644–653 (2015).
pubmed: 25670791
pmcid: 4325374
doi: 10.1242/dev.113357
Lin, G., Xu, N. & Xi, R. Paracrine Wingless signalling controls self-renewal of Drosophila intestinal stem cells. Nature 455, 1119–1123 (2008).
pubmed: 18806781
doi: 10.1038/nature07329
Xu, N. et al. EGFR, Wingless and JAK/STAT signaling cooperatively maintain Drosophila intestinal stem cells. Dev. Biol. 354, 31–43 (2011).
pubmed: 21440535
doi: 10.1016/j.ydbio.2011.03.018
Li, Z., Zhang, Y., Han, L., Shi, L. & Lin, X. Trachea-derived Dpp controls adult midgut homeostasis in Drosophila. Dev. Cell 24, 133–143 (2013).
pubmed: 23369712
doi: 10.1016/j.devcel.2012.12.010
Miguel-Aliaga, I., Jasper, H. & Lemaitre, B. Anatomy and physiology of the digestive tract of Drosophila melanogaster. Genetics 210, 357–396 (2018).
pubmed: 30287514
pmcid: 6216580
doi: 10.1534/genetics.118.300224
Kux, K. & Pitsouli, C. Tissue communication in regenerative inflammatory signaling: lessons from the fly gut. Front. Cell Infect. Microbiol. 4, 49 (2014).
pubmed: 24795868
pmcid: 4006025
doi: 10.3389/fcimb.2014.00049
Jiang, H. et al. Cytokine/Jak/Stat signaling mediates regeneration and homeostasis in the Drosophila midgut. Cell 137, 1343–1355 (2009).
pubmed: 19563763
pmcid: 2753793
doi: 10.1016/j.cell.2009.05.014
Buchon, N., Broderick, N. A., Poidevin, M., Pradervand, S. & Lemaitre, B. Drosophila intestinal response to bacterial infection: activation of host defense and stem cell proliferation. Cell Host Microbe 5, 200–211 (2009).
pubmed: 19218090
doi: 10.1016/j.chom.2009.01.003
Apidianakis, Y., Pitsouli, C., Perrimon, N. & Rahme, L. Synergy between bacterial infection and genetic predisposition in intestinal dysplasia. Proc. Natl Acad. Sci. USA 106, 20883–20888 (2009).
pubmed: 19934041
pmcid: 2791635
doi: 10.1073/pnas.0911797106
Amcheslavsky, A., Jiang, J. & Ip, Y. T. Tissue damage-induced intestinal stem cell division in Drosophila. Cell Stem Cell 4, 49–61 (2009).
pubmed: 19128792
pmcid: 2659574
doi: 10.1016/j.stem.2008.10.016
Biteau, B., Hochmuth, C. E. & Jasper, H. JNK activity in somatic stem cells causes loss of tissue homeostasis in the aging Drosophila gut. Cell Stem Cell 3, 442–455 (2008).
pubmed: 18940735
pmcid: 3225008
doi: 10.1016/j.stem.2008.07.024
Markstein, M. et al. Systematic screen of chemotherapeutics in Drosophila stem cell tumors. Proc. Natl Acad. Sci. USA 111, 4530–4535 (2014).
pubmed: 24616500
pmcid: 3970492
doi: 10.1073/pnas.1401160111
Linneweber, G. A. et al. Neuronal control of metabolism through nutrient-dependent modulation of tracheal branching. Cell 156, 69–83 (2014).
pubmed: 24439370
pmcid: 3898607
doi: 10.1016/j.cell.2013.12.008
Campbell, K. et al. Collective cell migration and metastases induced by an epithelial-to-mesenchymal transition in Drosophila intestinal tumors. Nat. Commun. 10, 2311 (2019).
pubmed: 31127094
pmcid: 6534551
doi: 10.1038/s41467-019-10269-y
Brand, A. H. & Perrimon, N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118, 401–415 (1993).
pubmed: 8223268
doi: 10.1242/dev.118.2.401
Shiga, Y., Tanaka-Matakatsu, M. & Hayashi, S. A nuclear GFP/β-galactosidase fusion protein as a marker for morphogenesis in living Drosophila. Dev. Growth Differ. 38, 99–106 (1996).
doi: 10.1046/j.1440-169X.1996.00012.x
Potter, C. J., Tasic, B., Russler, E. V., Liang, L. & Luo, L. The Q system: a repressible binary system for transgene expression, lineage tracing, and mosaic analysis. Cell 141, 536–548 (2010).
pubmed: 20434990
pmcid: 2883883
doi: 10.1016/j.cell.2010.02.025
Sutherland, D., Samakovlis, C. & Krasnow, M. A. branchless encodes a Drosophila FGF homolog that controls tracheal cell migration and the pattern of branching. Cell 87, 1091–1101 (1996).
pubmed: 8978613
doi: 10.1016/S0092-8674(00)81803-6
Grifoni, D., Sollazzo, M., Fontana, E., Froldi, F. & Pession, A. Multiple strategies of oxygen supply in Drosophila malignancies identify tracheogenesis as a novel cancer hallmark. Sci. Rep. 5, 9061 (2015).
pubmed: 25762498
pmcid: 4357021
doi: 10.1038/srep09061
Wang, C. W., Purkayastha, A., Jones, K. T., Thaker, S. K. & Banerjee, U. In vivo genetic dissection of tumor growth and the Warburg effect. eLife 5, e18126 (2016).
pubmed: 27585295
pmcid: 5030086
doi: 10.7554/eLife.18126
Kaelin, W. G. Jr. The von Hippel–Lindau protein, HIF hydroxylation, and oxygen sensing. Biochem. Biophys. Res. Commun. 338, 627–638 (2005).
pubmed: 16153592
doi: 10.1016/j.bbrc.2005.08.165
Klimova, T. & Chandel, N. S. Mitochondrial complex III regulates hypoxic activation of HIF. Cell Death Differ. 15, 660–666 (2008).
pubmed: 18219320
doi: 10.1038/sj.cdd.4402307
Semenza, G. L. Hypoxia-inducible factors: coupling glucose metabolism and redox regulation with induction of the breast cancer stem cell phenotype. EMBO J. 36, 252–259 (2017).
pubmed: 28007895
doi: 10.15252/embj.201695204
Movafagh, S., Crook, S. & Vo, K. Regulation of hypoxia-inducible factor-1a by reactive oxygen species: new developments in an old debate. J. Cell Biochem. 116, 696–703 (2015).
pubmed: 25546605
doi: 10.1002/jcb.25074
Lavista-Llanos, S. et al. Control of the hypoxic response in Drosophila melanogaster by the basic helix-loop-helix PAS protein Similar. Mol. Cell Biol. 22, 6842–6853 (2002).
pubmed: 12215541
pmcid: 134029
doi: 10.1128/MCB.22.19.6842-6853.2002
Centanin, L., Ratcliffe, P. J. & Wappner, P. Reversion of lethality and growth defects in Fatiga oxygen-sensor mutant flies by loss of hypoxia-inducible factor-α/Sima. EMBO Rep. 6, 1070–1075 (2005).
pubmed: 16179946
pmcid: 1371028
doi: 10.1038/sj.embor.7400528
Majmundar, A. J., Wong, W. J. & Simon, M. C. Hypoxia-inducible factors and the response to hypoxic stress. Mol. Cell 40, 294–309 (2010).
pubmed: 20965423
pmcid: 3143508
doi: 10.1016/j.molcel.2010.09.022
Tamamouna, V. & Pitsouli, C. The hypoxia-inducible factor-1α in angiogenesis and cancer: insights from the Drosophila model. Gene Expression and Regulation in Mammalian Cells—Transcription Toward the Establishment of Novel Therapeutics (ed. Uchiumi, F.) 209–241 (IntechOpen, 2018).
Deziel, E. et al. The contribution of MvfR to Pseudomonas aeruginosa pathogenesis and quorum sensing circuitry regulation: multiple quorum sensing-regulated genes are modulated without affecting lasRI, rhlRI or the production of N-acyl-L-homoserine lactones. Mol. Microbiol. 55, 998–1014 (2005).
pubmed: 15686549
doi: 10.1111/j.1365-2958.2004.04448.x
Xiao, G. et al. MvfR, a key Pseudomonas aeruginosa pathogenicity LTTR-class regulatory protein, has dual ligands. Mol. Microbiol. 62, 1689–1699 (2006).
pubmed: 17083468
doi: 10.1111/j.1365-2958.2006.05462.x
Liberati, N. T. et al. An ordered, nonredundant library of Pseudomonas aeruginosa strain PA14 transposon insertion mutants. Proc. Natl Acad. Sci. USA 103, 2833–2838 (2006).
pubmed: 16477005
pmcid: 1413827
doi: 10.1073/pnas.0511100103
Lee, K. A. et al. Bacterial-derived uracil as a modulator of mucosal immunity and gut-microbe homeostasis in Drosophila. Cell 153, 797–811 (2013).
pubmed: 23663779
doi: 10.1016/j.cell.2013.04.009
Hochmuth, C. E., Biteau, B., Bohmann, D. & Jasper, H. Redox regulation by Keap1 and Nrf2 controls intestinal stem cell proliferation in Drosophila. Cell Stem Cell 8, 188–199 (2011).
pubmed: 21295275
pmcid: 3035938
doi: 10.1016/j.stem.2010.12.006
Patel, P. H. et al. Damage sensing by a Nox–Ask1–MKK3–p38 signaling pathway mediates regeneration in the adult Drosophila midgut. Nat. Commun. 10, 4365 (2019).
pubmed: 31554796
pmcid: 6761285
doi: 10.1038/s41467-019-12336-w
Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 144, 646–674 (2011).
pubmed: 21376230
doi: 10.1016/j.cell.2011.02.013
Zhai, Z. et al. Accumulation of differentiating intestinal stem cell progenies drives tumorigenesis. Nat. Commun. 6, 10219 (2015).
pubmed: 26690827
doi: 10.1038/ncomms10219
McGuire, S. E., Mao, Z. & Davis, R. L. Spatiotemporal gene expression targeting with the TARGET and gene-switch systems in Drosophila. Sci. STKE 2004, pI6 (2004).
doi: 10.1126/stke.2202004pl6
Buchon, N. et al. Morphological and molecular characterization of adult midgut compartmentalization in Drosophila. Cell Rep. 3, 1725–1738 (2013).
pubmed: 23643535
doi: 10.1016/j.celrep.2013.04.001
Marianes, A. & Spradling, A. C. Physiological and stem cell compartmentalization within the Drosophila midgut. eLife 2, e00886 (2013).
pubmed: 23991285
pmcid: 3755342
doi: 10.7554/eLife.00886
Potente, M., Gerhardt, H. & Carmeliet, P. Basic and therapeutic aspects of angiogenesis. Cell 146, 873–887 (2011).
pubmed: 21925313
doi: 10.1016/j.cell.2011.08.039
Trinchieri, G. Cancer and inflammation: an old intuition with rapidly evolving new concepts. Annu. Rev. Immunol. 30, 677–706 (2012).
pubmed: 22224761
doi: 10.1146/annurev-immunol-020711-075008
Folkman, J. Tumor angiogenesis: therapeutic implications. N. Engl. J. Med. 285, 1182–1186 (1971).
pubmed: 4938153
doi: 10.1056/NEJM197111182852108
Folkman, J. Fundamental concepts of the angiogenic process. Curr. Mol. Med. 3, 643–651 (2003).
pubmed: 14601638
doi: 10.2174/1566524033479465
Weis, S. M. & Cheresh, D. A. Tumor angiogenesis: molecular pathways and therapeutic targets. Nat. Med. 17, 1359–1370 (2011).
pubmed: 22064426
doi: 10.1038/nm.2537
Choudhry, H. & Harris, A. L. Advances in hypoxia-inducible factor biology. Cell Metab. 27, 281–298 (2018).
pubmed: 29129785
doi: 10.1016/j.cmet.2017.10.005
Lee, P., Chandel, N. S. & Simon, M. C. Cellular adaptation to hypoxia through hypoxia inducible factors and beyond. Nat. Rev. Mol. Cell Biol. 6, 268–283 (2020).
doi: 10.1038/s41580-020-0227-y
Takenaga, K. Angiogenic signaling aberrantly induced by tumor hypoxia. Front Biosci. (Landmark Ed.) 16, 31–48 (2011).
doi: 10.2741/3674
Perochon, J., Yu, Y., Aughey, G. N., Southall, T. D. & Cordero, J. B. Dynamic adult tracheal plasticity drives stem cell adaptation to changes in intestinal homeostasis. Nat. Cell Bio. (2021).
Ohshiro, T. & Saigo, K. Transcriptional regulation of breathless FGF receptor gene by binding of TRACHEALESS/dARNT heterodimers to three central midline elements in Drosophila developing trachea. Development 124, 3975–3986 (1997).
pubmed: 9374395
doi: 10.1242/dev.124.20.3975
Santabarbara-Ruiz, P. et al. ROS-induced JNK and p38 signaling is required for unpaired cytokine activation during Drosophila regeneration. PLoS Genet. 11, e1005595 (2015).
pubmed: 26496642
pmcid: 4619769
doi: 10.1371/journal.pgen.1005595
André-Lévigne, D., Modarressi, A., Pepper, M. S. & Pittet-Cuénod, B. Reactive oxygen species and NOX enzymes are emerging as key players in cutaneous wound repair. Int. J. Mol. Sci. 18, 2149 (2017).
pmcid: 5666831
doi: 10.3390/ijms18102149
Jia, Y.-T. et al. Activation of p38 MAPK by reactive oxygen species is essential in a rat model of stress-induced gastric mucosal injury. J. Immunol. 179, 7808–7819 (2007).
pubmed: 18025227
doi: 10.4049/jimmunol.179.11.7808
Warren, C. M., Ziyad, S., Briot, A., Der, A. & Iruela-Arispe, M. L. A ligand-independent VEGFR2 signaling pathway limits angiogenic responses in diabetes. Sci. Signal. 7, ra1 (2014).
pubmed: 24399295
pmcid: 4030697
doi: 10.1126/scisignal.2004235
Nezu, M. et al. Nrf2 inactivation enhances placental angiogenesis in a preeclampsia mouse model and improves maternal and fetal outcomes. Sci. Signal 10, eaam5711 (2017).
pubmed: 28512147
doi: 10.1126/scisignal.aam5711
Reczek, C. & Chandel, N. The two faces of reactive oxygen species in cancer. Annu. Rev. Cancer Biol. 1, 79–98 (2017).
doi: 10.1146/annurev-cancerbio-041916-065808
Perez, E., Lindblad, J. L. & Bergmann, A. Tumor-promoting function of apoptotic caspases by an amplification loop involving ROS, macrophages and JNK in Drosophila. eLife 6, e26747 (2017).
pubmed: 28853394
pmcid: 5779227
doi: 10.7554/eLife.26747
Ha, E.-M. et al. An antioxidant system required for host protection against gut infection in Drosophila. Dev. Cell 8, 125–132 (2005).
pubmed: 15621536
doi: 10.1016/j.devcel.2004.11.007
Lee, W. J. & Brey, P. T. How microbiomes influence metazoan development: insights from history and Drosophila modeling of gut–microbe interactions. Annu. Rev. Cell Dev. Biol. 29, 571–592 (2013).
pubmed: 23808845
doi: 10.1146/annurev-cellbio-101512-122333
Jones, R. M. et al. Symbiotic lactobacilli stimulate gut epithelial proliferation via Nox-mediated generation of reactive oxygen species. EMBO J. 32, 3017–3028 (2013).
pubmed: 24141879
pmcid: 3844951
doi: 10.1038/emboj.2013.224
Kim, S. H. & Lee, W. J. Role of DUOX in gut inflammation: lessons from Drosophila model of gut–microbiota interactions. Front. Cell Infect. Microbiol. 3, 116 (2014).
pubmed: 24455491
pmcid: 3887270
doi: 10.3389/fcimb.2013.00116
Jang, S. et al. Dual oxidase enables insect gut symbiosis by mediating respiratory network formation. Proc. Natl Acad. Sci. USA 118, e2020922118 (2021).
pubmed: 33649233
pmcid: 7958442
doi: 10.1073/pnas.2020922118
Pitsouli, C. & Perrimon, N. Embryonic multipotent progenitors remodel the Drosophila airways during metamorphosis. Development 137, 3615–3624 (2010).
pubmed: 20940225
pmcid: 2964094
doi: 10.1242/dev.056408
Gervais, L. & Casanova, J. The Drosophila homologue of SRF acts as a boosting mechanism to sustain FGF-induced terminal branching in the tracheal system. Development 138, 1269–1274 (2011).
pubmed: 21385762
doi: 10.1242/dev.059188
Bardin, A. J., Perdigoto, C. N., Southall, T. D., Brand, A. H. & Schweisguth, F. Transcriptional control of stem cell maintenance in the Drosophila intestine. Development 137, 705–714 (2010).
pubmed: 20147375
pmcid: 2827683
doi: 10.1242/dev.039404
Sato, M. & Kornberg, T. B. FGF is an essential mitogen and chemoattractant for the air sacs of the Drosophila tracheal system. Dev. Cell 3, 195–207 (2002).
pubmed: 12194851
doi: 10.1016/S1534-5807(02)00202-2
Kumar, J. P. & Moses, K. EGF receptor and Notch signaling act upstream of Eyeless/Pax6 to control eye specification. Cell 104, 687–697 (2001).
pubmed: 11257223
doi: 10.1016/S0092-8674(01)00265-3
Ha, E. M., Oh, C. T., Bae, Y. S. & Lee, W. J. A direct role for dual oxidase in Drosophila gut immunity. Science 310, 847–850 (2005).
pubmed: 16272120
doi: 10.1126/science.1117311
Thibault, S. T. et al. A complementary transposon tool kit for Drosophila melanogaster using P and piggyBac. Nat. Genet. 36, 283–287 (2004).
pubmed: 14981521
doi: 10.1038/ng1314
Lee, T. & Luo, L. Mosaic analysis with a repressible cell marker (MARCM) for Drosophila neural development. Trends Neurosci. 24, 251–254 (2001).
pubmed: 11311363
doi: 10.1016/S0166-2236(00)01791-4
Pitsouli, C. & Delidakis, C. The interplay between DSL proteins and ubiquitin ligases in Notch signaling. Development 132, 4041–4050 (2005).
pubmed: 16093323
doi: 10.1242/dev.01979