Abstract
The Drosophila adult has an intestine composed of a series of differentiated cells and tissue stem cells, all of which are similar to the mammalian intestinal cells. The aged adult intestine shows apparent characteristics such as multilayering of absorptive cells, misexpression of cell type-specific genes, and hyperproliferation of stem cells. Recent studies have revealed various gene networks responsible for progression of these aged phenotypes. The molecular mechanism for senescence of the Drosophila adult midgut and its relation with the corresponding mechanism in mammals are overviewed. In addition, a basic method for observing aged phenotypes of the midgut is described.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Adachi-Yamada T, Fujimura-Kamada K, Nishida Y, Matsumoto K. Distortion of proximodistal information causes JNK-dependent apoptosis in Drosophila wing. Nature. 1999a;400(6740):166–9. https://doi.org/10.1038/22112.
Adachi-Yamada T, Nakamura M, Irie K, Tomoyasu Y, Sano Y, Mori E, Goto S, Ueno N, Nishida Y, Matsumoto K. p38 mitogen-activated protein kinase can be involved in transforming growth factor beta superfamily signal transduction in Drosophila wing morphogenesis. Mol Cell Biol. 1999b;19(3):2322–9.
Bagowski CP, Besser J, Frey CR, Ferrell JE Jr. The JNK cascade as a biochemical switch in mammalian cells: ultrasensitive and all-or-none responses. Curr Biol CB. 2003;13(4):315–20.
Balakireva M, Stocker RF, Gendre N, Ferveur JF. Voila, a new Drosophila courtship variant that affects the nervous system: behavioral, neural, and genetic characterization. J Neurosci. 1998;18(11):4335–43.
Beehler-Evans R, Micchelli CA. Generation of enteroendocrine cell diversity in midgut stem cell lineages. Development. 2015;142(4):654–64. https://doi.org/10.1242/dev.114959.
Biteau B, Hochmuth CE, Jasper H. JNK activity in somatic stem cells causes loss of tissue homeostasis in the aging Drosophila gut. Cell Stem Cell. 2008;3(4):442–55. https://doi.org/10.1016/j.stem.2008.07.024.
Bloom SR, Polak JM. Gut hormones. Adv Clin Chem. 1980;21:177–244.
Buchon N, Broderick NA, Chakrabarti S, Lemaitre B. Invasive and indigenous microbiota impact intestinal stem cell activity through multiple pathways in Drosophila. Genes Dev. 2009;23(19):2333–44. https://doi.org/10.1101/gad.1827009.
Buchon N, Osman D, David FP, Fang HY, Boquete JP, Deplancke B, Lemaitre B. Morphological and molecular characterization of adult midgut compartmentalization in Drosophila. Cell Rep. 2013;3(5):1725–38. https://doi.org/10.1016/j.celrep.2013.04.001.
Choi NH, Kim JG, Yang DJ, Kim YS, Yoo MA. Age-related changes in Drosophila midgut are associated with PVF2, a PDGF/VEGF-like growth factor. Aging Cell. 2008;7(3):318–34. https://doi.org/10.1111/j.1474-9726.2008.00380.x.
Cordero JB, Stefanatos RK, Scopelliti A, Vidal M, Sansom OJ. Inducible progenitor-derived wingless regulates adult midgut regeneration in Drosophila. EMBO J. 2012;31(19):3901–17. https://doi.org/10.1038/emboj.2012.248.
De Loof A, Schoofs L. Homologies between the amino acid sequences of some vertebrate peptide hormones and peptides isolated from invertebrate sources. Comp Biochem Physiol B Comp Biochem. 1990;95(3):459–68.
Endo Y, Iwanaga T, Fujita T. Gut endocrine cells of invertebrates. Prog Clin Biol Res. 1990;342:499–503.
Fang HY, Martinez-Arias A, de Navascués J (2016) Autocrine and paracrine Wingless signalling in the Drosophila midgut by both continuous gradient and asynchronous bursts of Wingless expression. F1000Research 5:317. doi:https://doi.org/10.12688/f1000research.8170.1.
Fujita T, Kanno T, Kobayashi S. The Paraneuron. Tokyo: Springer; 2012.
Goulas S, Conder R, Knoblich JA. The par complex and integrins direct asymmetric cell division in adult intestinal stem cells. Cell Stem Cell. 2012;11(4):529–40. https://doi.org/10.1016/j.stem.2012.06.017.
Jiang H, Edgar BA. EGFR signaling regulates the proliferation of Drosophila adult midgut progenitors. Development. 2009;136(3):483–93. https://doi.org/10.1242/dev.026955.
Jiang H, Patel PH, Kohlmaier A, Grenley MO, McEwen DG, Edgar BA. Cytokine/Jak/Stat signaling mediates regeneration and homeostasis in the Drosophila midgut. Cell. 2009;137(7):1343–55. https://doi.org/10.1016/j.cell.2009.05.014.
Jiang H, Grenley MO, Bravo MJ, Blumhagen RZ, Edgar BA. EGFR/Ras/MAPK signaling mediates adult midgut epithelial homeostasis and regeneration in Drosophila. Cell Stem Cell. 2011;8(1):84–95. https://doi.org/10.1016/j.stem.2010.11.026.
Karpowicz P, Perez J, Perrimon N. The hippo tumor suppressor pathway regulates intestinal stem cell regeneration. Development. 2010;137(24):4135–45. https://doi.org/10.1242/dev.060483.
Kuwamura M, Maeda K, Adachi-Yamada T. Mathematical modelling and experiments for the proliferation and differentiation of Drosophila intestinal stem cells I. J Biol Dyn. 2010;4(3):248–57. https://doi.org/10.1080/17513750903045635.
Kuwamura M, Maeda K, Adachi-Yamada T. Mathematical modelling and experiments for the proliferation and differentiation of Drosophila intestinal stem cells II. J Biol Dyn. 2012;6:267–76. https://doi.org/10.1080/17513758.2011.560290.
Li H, Qi Y, Jasper H. Preventing age-related decline of gut compartmentalization limits microbiota Dysbiosis and extends lifespan. Cell Host Microbe. 2016;19(2):240–53. https://doi.org/10.1016/j.chom.2016.01.008.
Lin G, Xu N, Xi R. Paracrine wingless signalling controls self-renewal of Drosophila intestinal stem cells. Nature. 2008;455(7216):1119–23. https://doi.org/10.1038/nature07329.
Lin G, Zhang X, Ren J, Pang Z, Wang C, Xu N, Xi R. Integrin signaling is required for maintenance and proliferation of intestinal stem cells in Drosophila. Dev Biol. 2013;377(1):177–87. https://doi.org/10.1016/j.ydbio.2013.01.032.
Maeda K, Takemura M, Umemori M, Adachi-Yamada T. E-cadherin prolongs the moment for interaction between intestinal stem cell and its progenitor cell to ensure notch signaling in adult Drosophila midgut. Genes Cells Devoted Mol Cell Mech. 2008;13(12):1219–27. https://doi.org/10.1111/j.1365-2443.2008.01239.x.
Man AL, Bertelli E, Rentini S, Regoli M, Briars G, Marini M, Watson AJ, Nicoletti C. Age-associated modifications of intestinal permeability and innate immunity in human small intestine. Clin Sci (London, England: 1979). 2015;129(7):515–27. https://doi.org/10.1042/cs20150046.
Martin-Blanco E, Gampel A, Ring J, Virdee K, Kirov N, Tolkovsky AM, Martinez-Arias A. Puckered encodes a phosphatase that mediates a feedback loop regulating JNK activity during dorsal closure in Drosophila. Genes Dev. 1998;12(4):557–70.
Micchelli CA, Perrimon N. Evidence that stem cells reside in the adult Drosophila midgut epithelium. Nature. 2006;439(7075):475–9. https://doi.org/10.1038/nature04371.
Mitsuoka T. Intestinal flora and human health. Asia Pac J Clin Nutr. 1996;5(1):2–9.
Nalapareddy K, Nattamai KJ, Kumar RS, Karns R, Wikenheiser-Brokamp KA, Sampson LL, Mahe MM, Sundaram N, Yacyshyn MB, Yacyshyn B, Helmrath MA, Zheng Y, Geiger H. Canonical Wnt signaling ameliorates aging of intestinal stem cells. Cell Rep. 2017;18(11):2608–21. https://doi.org/10.1016/j.celrep.2017.02.056.
Ohlstein B, Spradling A. The adult Drosophila posterior midgut is maintained by pluripotent stem cells. Nature. 2006;439(7075):470–4. https://doi.org/10.1038/nature04333.
Okumura T, Takeda K, Taniguchi K, Adachi-Yamada T. Betanu integrin inhibits chronic and high level activation of JNK to repress senescence phenotypes in Drosophila adult midgut. PLoS One. 2014;9(2):e89387. https://doi.org/10.1371/journal.pone.0089387.
Okumura T, Takeda K, Kuchiki M, Akaishi M, Taniguchi K, Adachi-Yamada T. GATAe regulates intestinal stem cell maintenance and differentiation in Drosophila adult midgut. Dev Biol. 2016;410(1):24–35. https://doi.org/10.1016/j.ydbio.2015.12.017.
Patel PH, Dutta D, Edgar BA. Niche appropriation by Drosophila intestinal stem cell tumours. Nat Cell Biol. 2015;17(9):1182–92. https://doi.org/10.1038/ncb3214.
Perdigoto CN, Schweisguth F, Bardin AJ. Distinct levels of notch activity for commitment and terminal differentiation of stem cells in the adult fly intestine. Development. 2011;138(21):4585–95. https://doi.org/10.1242/dev.065292.
Regan JC, Brandao AS, Leitao AB, Mantas Dias AR, Sucena E, Jacinto A, Zaidman-Remy A. Steroid hormone signaling is essential to regulate innate immune cells and fight bacterial infection in Drosophila. PLoS Pathog. 2013;9(10):e1003720. https://doi.org/10.1371/journal.ppat.1003720.
Shaw RL, Kohlmaier A, Polesello C, Veelken C, Edgar BA, Tapon N. The Hippo pathway regulates intestinal stem cell proliferation during Drosophila adult midgut regeneration. Development. 2010;137(24):4147–58. https://doi.org/10.1242/dev.052506.
Takeda K, Okumura T, Terahata M, Yamaguchi M, Taniguchi K, Adachi-Yamada T. Drosophila peptide hormones Allatostatin a and diuretic hormone 31 with complementary gradient distribution in posterior midgut antagonistically regulate midgut senescence and adult lifespan. Zool Sci in press. 2018. https://doi.org/10.2108/zs170099.
Wang MC, Bohmann D, Jasper H. JNK signaling confers tolerance to oxidative stress and extends lifespan in Drosophila. Dev Cell. 2003;5(5):811–6.
Wang MC, Bohmann D, Jasper H. JNK extends life span and limits growth by antagonizing cellular and organism-wide responses to insulin signaling. Cell. 2005;121(1):115–25. https://doi.org/10.1016/j.cell.2005.02.030.
Xu N, Wang SQ, Tan D, Gao Y, Lin G, Xi R. EGFR, wingless and JAK/STAT signaling cooperatively maintain Drosophila intestinal stem cells. Dev Biol. 2011;354(1):31–43. https://doi.org/10.1016/j.ydbio.2011.03.018.
Zeng X, Chauhan C, Hou SX. Characterization of midgut stem cell- and enteroblast-specific Gal4 lines in drosophila. Genesis (New York, NY: 2000). 2010;48(10):607–11. https://doi.org/10.1002/dvg.20661.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Takeda, K., Okumura, T., Taniguchi, K., Adachi-Yamada, T. (2018). Adult Intestine Aging Model. In: Yamaguchi, M. (eds) Drosophila Models for Human Diseases. Advances in Experimental Medicine and Biology, vol 1076. Springer, Singapore. https://doi.org/10.1007/978-981-13-0529-0_2
Download citation
DOI: https://doi.org/10.1007/978-981-13-0529-0_2
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-13-0528-3
Online ISBN: 978-981-13-0529-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)