Skip to main content
SpringerLink
Log in

Intestinal stem cell response to injury: lessons from Drosophila

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

Many adult tissues and organs are maintained by resident stem cells that are activated in response to injury but the mechanisms that regulate stem cell activity during regeneration are still poorly understood. An emerging system to study such problem is the Drosophila adult midgut. Recent studies have identified both intrinsic factors and extrinsic niche signals that control the proliferation, self-renewal, and lineage differentiation of Drosophila adult intestinal stem cells (ISCs). These findings set up the stage to interrogate how niche signals are regulated and how they are integrated with cell-intrinsic factors to control ISC activity during normal homeostasis and regeneration. Here we review the current understanding of the mechanisms that control ISC self-renewal, proliferation, and lineage differentiation in Drosophila adult midgut with a focus on the niche signaling network that governs ISC activity in response to injury.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Buchon N, Osman D, David FP, Fang HY, Boquete JP, Deplancke B, Lemaitre B (2013) Morphological and molecular characterization of adult midgut compartmentalization in Drosophila. Cell Rep 3(5):1725–1738. doi:10.1016/j.celrep.2013.04.001

    Article  CAS  PubMed  Google Scholar 

  2. Ohlstein B, Spradling A (2006) The adult Drosophila posterior midgut is maintained by pluripotent stem cells. Nature 439(7075):470–474

    Article  CAS  PubMed  Google Scholar 

  3. Micchelli CA, Perrimon N (2006) Evidence that stem cells reside in the adult Drosophila midgut epithelium. Nature 439(7075):475–479

    Article  CAS  PubMed  Google Scholar 

  4. Jiang H, Edgar BA (2009) EGFR signaling regulates the proliferation of Drosophila adult midgut progenitors. Development 136(3):483–493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Mathur D, Bost A, Driver I, Ohlstein B (2010) A transient niche regulates the specification of Drosophila intestinal stem cells. Science 327(5962):210–213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Micchelli CA, Sudmeier L, Perrimon N, Tang S, Beehler-Evans R (2010) Identification of adult midgut precursors in Drosophila. Gene Expr Patterns 11(1–2):12–21

    PubMed  Google Scholar 

  7. Takashima S, Adams KL, Ortiz PA, Ying CT, Moridzadeh R, Younossi-Hartenstein A, Hartenstein V (2011) Development of the Drosophila entero-endocrine lineage and its specification by the Notch signaling pathway. Dev Biol 353(2):161–172

    Article  CAS  PubMed  Google Scholar 

  8. Ohlstein B, Spradling A (2007) Multipotent Drosophila intestinal stem cells specify daughter cell fates by differential notch signaling. Science 315(5814):988–992

    Article  CAS  PubMed  Google Scholar 

  9. O’Brien LE, Soliman SS, Li X, Bilder D (2011) Altered modes of stem cell division drive adaptive intestinal growth. Cell 147(3):603–614. doi:10.1016/j.cell.2011.08.048

    Article  PubMed  PubMed Central  Google Scholar 

  10. Goulas S, Conder R, Knoblich JA (2012) The Par complex and integrins direct asymmetric cell division in adult intestinal stem cells. Cell Stem Cell 11(4):529–540. doi:10.1016/j.stem.2012.06.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Tian A, Jiang J (2014) Intestinal epithelium-derived BMP controls stem cell self-renewal in Drosophila adult midgut. Elife 3:e01857. doi:10.7554/eLife.01857

    Article  PubMed  PubMed Central  Google Scholar 

  12. de Navascues J, Perdigoto CN, Bian Y, Schneider MH, Bardin AJ, Martinez-Arias A, Simons BD (2012) Drosophila midgut homeostasis involves neutral competition between symmetrically dividing intestinal stem cells. EMBO J 31(11):2473–2485. doi:10.1038/emboj.2012.106

    Article  PubMed  PubMed Central  Google Scholar 

  13. Jiang H, Patel PH, Kohlmaier A, Grenley MO, McEwen DG, Edgar BA (2009) Cytokine/Jak/Stat signaling mediates regeneration and homeostasis in the Drosophila midgut. Cell 137(7):1343–1355

    Article  PubMed  PubMed Central  Google Scholar 

  14. Antonello ZA, Reiff T, Ballesta-Illan E, Dominguez M (2015) Robust intestinal homeostasis relies on cellular plasticity in enteroblasts mediated by miR-8-Escargot switch. EMBO J 34(15):2025–2041. doi:10.15252/embj.201591517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Amcheslavsky A, Jiang J, Ip YT (2009) Tissue damage-induced intestinal stem cell division in Drosophila. Cell Stem Cell 4(1):49–61

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Buchon N, Broderick NA, Poidevin M, Pradervand S, Lemaitre B (2009) Drosophila intestinal response to bacterial infection: activation of host defense and stem cell proliferation. Cell Host Microbe 5(2):200–211

    Article  CAS  PubMed  Google Scholar 

  17. Apidianakis Y, Pitsouli C, Perrimon N, Rahme L (2009) Synergy between bacterial infection and genetic predisposition in intestinal dysplasia. Proc Natl Acad Sci USA. doi:10.1073/pnas.0911797106

    PubMed  PubMed Central  Google Scholar 

  18. Biteau B, Hochmuth CE, Jasper H (2008) JNK activity in somatic stem cells causes loss of tissue homeostasis in the aging Drosophila gut. Cell Stem Cell 3(4):442–455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Buchon N, Broderick NA, Chakrabarti S, Lemaitre B (2009) Invasive and indigenous microbiota impact intestinal stem cell activity through multiple pathways in Drosophila. Genes Dev 23(19):2333–2344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Biteau B, Hochmuth CE, Jasper H (2011) Maintaining tissue homeostasis: dynamic control of somatic stem cell activity. Cell Stem Cell 9(5):402–411. doi:10.1016/j.stem.2011.10.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Patel PH, Dutta D, Edgar BA (2015) Niche appropriation by Drosophila intestinal stem cell tumours. Nat Cell Biol 17(9):1182–1192. doi:10.1038/ncb3214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Siudeja K, Nassari S, Gervais L, Skorski P, Lameiras S, Stolfa D, Zande M, Bernard V, Rio Frio T, Bardin AJ (2015) Frequent somatic mutation in adult intestinal stem cells drives neoplasia and genetic mosaicism during aging. Cell Stem Cell 17(6):663–674. doi:10.1016/j.stem.2015.09.016

    Article  CAS  PubMed  Google Scholar 

  23. Bardin AJ, Perdigoto CN, Southall TD, Brand AH, Schweisguth F (2010) Transcriptional control of stem cell maintenance in the Drosophila intestine. Development 137(5):705–714

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Montagne C, Gonzalez-Gaitan M (2014) Sara endosomes and the asymmetric division of intestinal stem cells. Development 141(10):2014–2023. doi:10.1242/dev.104240

    Article  CAS  PubMed  Google Scholar 

  25. Amcheslavsky A, Ito N, Jiang J, Ip YT (2011) Tuberous sclerosis complex and Myc coordinate the growth and division of Drosophila intestinal stem cells. J Cell Biol 193(4):695–710

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Choi NH, Lucchetta E, Ohlstein B (2011) Nonautonomous regulation of Drosophila midgut stem cell proliferation by the insulin-signaling pathway. Proc Natl Acad Sci USA 108(46):18702–18707. doi:10.1073/pnas.1109348108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Chen CH, Luhur A, Sokol N (2015) Lin-28 promotes symmetric stem cell division and drives adaptive growth in the adult Drosophila intestine. Development 142(20):3478–3487. doi:10.1242/dev.127951

    Article  CAS  PubMed  Google Scholar 

  28. Foronda D, Weng R, Verma P, Chen YW, Cohen SM (2014) Coordination of insulin and Notch pathway activities by microRNA miR-305 mediates adaptive homeostasis in the intestinal stem cells of the Drosophila gut. Genes Dev 28(21):2421–2431. doi:10.1101/gad.241588.114

    Article  PubMed  PubMed Central  Google Scholar 

  29. Zeng X, Hou SX (2015) Enteroendocrine cells are generated from stem cells through a distinct progenitor in the adult Drosophila posterior midgut. Development 142(4):644–653. doi:10.1242/dev.113357

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Biteau B, Jasper H (2014) Slit/Robo signaling regulates cell fate decisions in the intestinal stem cell lineage of Drosophila. Cell Rep 7(6):1867–1875. doi:10.1016/j.celrep.2014.05.024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Beehler-Evans R, Micchelli CA (2015) Generation of enteroendocrine cell diversity in midgut stem cell lineages. Development 142(4):654–664. doi:10.1242/dev.114959

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Guo Z, Ohlstein B (2015) Stem cell regulation. Bidirectional Notch signaling regulates Drosophila intestinal stem cell multipotency. Science 350 (6263):919–927. doi:10.1126/science.aab0988

  33. Zeng X, Lin X, Hou SX (2013) The Osa-containing SWI/SNF chromatin-remodeling complex regulates stem cell commitment in the adult Drosophila intestine. Development 140(17):3532–3540. doi:10.1242/dev.096891

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Wang C, Guo X, Dou K, Chen H, Xi R (2015) Ttk69 acts as a master repressor of enteroendocrine cell specification in Drosophila intestinal stem cell lineages. Development 142(19):3321–3331. doi:10.1242/dev.123208

    Article  CAS  PubMed  Google Scholar 

  35. Fre S, Huyghe M, Mourikis P, Robine S, Louvard D, Artavanis-Tsakonas S (2005) Notch signals control the fate of immature progenitor cells in the intestine. Nature 435(7044):964–968

    Article  CAS  PubMed  Google Scholar 

  36. van Es JH, van Gijn ME, Riccio O, van den Born M, Vooijs M, Begthel H, Cozijnsen M, Robine S, Winton DJ, Radtke F, Clevers H (2005) Notch/gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells. Nature 435(7044):959–963

    Article  PubMed  Google Scholar 

  37. Dutta D, Dobson AJ, Houtz PL, Glasser C, Revah J, Korzelius J, Patel PH, Edgar BA, Buchon N (2015) Regional cell-specific transcriptome mapping reveals regulatory complexity in the adult Drosophila midgut. Cell reports 12(2):346–358. doi:10.1016/j.celrep.2015.06.009

    Article  CAS  PubMed  Google Scholar 

  38. Marianes A, Spradling AC (2013) Physiological and stem cell compartmentalization within the Drosophila midgut. Elife 2:e00886. doi:10.7554/eLife.00886

    Article  PubMed  PubMed Central  Google Scholar 

  39. Strand M, Micchelli CA (2011) Quiescent gastric stem cells maintain the adult Drosophila stomach. Proc Natl Acad Sci USA 108(43):17696–17701. doi:10.1073/pnas.1109794108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Wang C, Guo X, Xi R (2014) EGFR and Notch signaling respectively regulate proliferative activity and multiple cell lineage differentiation of Drosophila gastric stem cells. Cell Res 24(5):610–627. doi:10.1038/cr.2014.27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Guo Z, Driver I, Ohlstein B (2013) Injury-induced BMP signaling negatively regulates Drosophila midgut homeostasis. J Cell Biol 201(6):945–961. doi:10.1083/jcb.201302049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Li H, Qi Y, Jasper H (2013) Dpp signaling determines regional stem cell identity in the regenerating adult Drosophila gastrointestinal tract. Cell reports 4(1):10–18. doi:10.1016/j.celrep.2013.05.040

    Article  PubMed  Google Scholar 

  43. van der Flier LG, van Gijn ME, Hatzis P, Kujala P, Haegebarth A, Stange DE, Begthel H, van den Born M, Guryev V, Oving I, van Es JH, Barker N, Peters PJ, van de Wetering M, Clevers H (2009) Transcription factor achaete scute-like 2 controls intestinal stem cell fate. Cell 136(5):903–912

    Article  PubMed  Google Scholar 

  44. Loza-Coll MA, Southall TD, Sandall SL, Brand AH, Jones DL (2014) Regulation of Drosophila intestinal stem cell maintenance and differentiation by the transcription factor Escargot. EMBO J 33(24):2983–2996. doi:10.15252/embj.201489050

    Article  PubMed  PubMed Central  Google Scholar 

  45. Korzelius J, Naumann SK, Loza-Coll MA, Chan JS, Dutta D, Oberheim J, Glasser C, Southall TD, Brand AH, Jones DL, Edgar BA (2014) Escargot maintains stemness and suppresses differentiation in Drosophila intestinal stem cells. EMBO J 33(24):2967–2982. doi:10.15252/embj.201489072

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Zhu LJ, Christensen RG, Kazemian M, Hull CJ, Enuameh MS, Basciotta MD, Brasefield JA, Zhu C, Asriyan Y, Lapointe DS, Sinha S, Wolfe SA, Brodsky MH (2011) FlyFactorSurvey: a database of Drosophila transcription factor binding specificities determined using the bacterial one-hybrid system. Nucleic Acids Res 39:D111–D117. doi:10.1093/nar/gkq858 (Database issue)

    Article  CAS  PubMed  Google Scholar 

  47. Biteau B, Jasper H (2011) EGF signaling regulates the proliferation of intestinal stem cells in Drosophila. Development 138(6):1045–1055

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Buchon N, Broderick NA, Kuraishi T, Lemaitre B (2010) Drosophila EGFR pathway coordinates stem cell proliferation and gut remodeling following infection. BMC Biol 8:152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Jiang H, Grenley MO, Bravo MJ, Blumhagen RZ, Edgar BA (2011) EGFR/Ras/MAPK signaling mediates adult midgut epithelial homeostasis and regeneration in Drosophila. Cell Stem Cell 8(1):84–95

    Article  CAS  PubMed  Google Scholar 

  50. Xu N, Wang SQ, Tan D, Gao Y, Lin G, Xi R (2011) EGFR, Wingless and JAK/STAT signaling cooperatively maintain Drosophila intestinal stem cells. Dev Biol 354:31–43

    Article  CAS  PubMed  Google Scholar 

  51. Liu W, Singh SR, Hou SX (2010) JAK-STAT is restrained by Notch to control cell proliferation of the Drosophila intestinal stem cells. J Cell Biochem 109(5):992–999

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Beebe K, Lee WC, Micchelli CA (2010) JAK/STAT signaling coordinates stem cell proliferation and multilineage differentiation in the Drosophila intestinal stem cell lineage. Dev Biol 338(1):28–37

    Article  CAS  PubMed  Google Scholar 

  53. Zhou F, Rasmussen A, Lee S, Agaisse H (2013) The UPD3 cytokine couples environmental challenge and intestinal stem cell division through modulation of JAK/STAT signaling in the stem cell microenvironment. Dev Biol 373(2):383–393. doi:10.1016/j.ydbio.2012.10.023

    Article  CAS  PubMed  Google Scholar 

  54. Lin G, Xu N, Xi R (2009) Paracrine unpaired signaling through the JAK/STAT pathway controls self-renewal and lineage differentiation of Drosophila intestinal stem cells. J Mol Cell Biol 2(1):37–49

    Article  PubMed  Google Scholar 

  55. Cronin SJ, Nehme NT, Limmer S, Liegeois S, Pospisilik JA, Schramek D, Leibbrandt A, Simoes Rde M, Gruber S, Puc U, Ebersberger I, Zoranovic T, Neely GG, von Haeseler A, Ferrandon D, Penninger JM (2009) Genome-wide RNAi screen identifies genes involved in intestinal pathogenic bacterial infection. Science 325(5938):340–343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Zhou J, Florescu S, Boettcher AL, Luo L, Dutta D, Kerr G, Cai Y, Edgar BA, Boutros M (2015) Dpp/Gbb signaling is required for normal intestinal regeneration during infection. Dev Biol 399(2):189–203. doi:10.1016/j.ydbio.2014.12.017

    Article  CAS  PubMed  Google Scholar 

  57. Scopelliti A, Cordero JB, Diao F, Strathdee K, White BH, Sansom OJ, Vidal M (2014) Local control of intestinal stem cell homeostasis by enteroendocrine cells in the adult Drosophila midgut. Curr Biol CB 24(11):1199–1211. doi:10.1016/j.cub.2014.04.007

    Article  CAS  PubMed  Google Scholar 

  58. Lee WC, Beebe K, Sudmeier L, Micchelli CA (2009) Adenomatous polyposis coli regulates Drosophila intestinal stem cell proliferation. Development 136(13):2255–2264

    Article  CAS  PubMed  Google Scholar 

  59. Cordero JB, Stefanatos RK, Scopelliti A, Vidal M, Sansom OJ (2012) Inducible progenitor-derived Wingless regulates adult midgut regeneration in Drosophila. EMBO J 31(19):3901–3917. doi:10.1038/emboj.2012.248

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Li Z, Zhang Y, Han L, Shi L, Lin X (2013) Trachea-derived dpp controls adult midgut homeostasis in Drosophila. Dev Cell 24(2):133–143. doi:10.1016/j.devcel.2012.12.010

    Article  PubMed  Google Scholar 

  61. Tian A, Shi Q, Jiang A, Li S, Wang B, Jiang J (2015) Injury-stimulated Hedgehog signaling promotes regenerative proliferation of Drosophila intestinal stem cells. J Cell Biol 208(6):807–819. doi:10.1083/jcb.201409025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Ren F, Wang B, Yue T, Yun EY, Ip YT, Jiang J (2010) Hippo signaling regulates Drosophila intestine stem cell proliferation through multiple pathways. Proc Natl Acad Sci USA 107(49):21064–21069

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Staley BK, Irvine KD (2010) Warts and Yorkie mediate intestinal regeneration by influencing stem cell proliferation. Curr Biol CB 20(17):1580–1587

    Article  CAS  PubMed  Google Scholar 

  64. Karpowicz P, Perez J, Perrimon N (2010) The Hippo tumor suppressor pathway regulates intestinal stem cell regeneration. Development 137(24):4135–4145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. van der Flier LG, Clevers H (2009) Stem cells, self-renewal, and differentiation in the intestinal epithelium. Annu Rev Physiol 71:241–260

    Article  PubMed  Google Scholar 

  66. Lin G, Xu N, Xi R (2008) Paracrine Wingless signalling controls self-renewal of Drosophila intestinal stem cells. Nature 455(7216):1119–1123

    Article  CAS  PubMed  Google Scholar 

  67. Cordero JB, Stefanatos RK, Myant K, Vidal M, Sansom OJ (2012) Non-autonomous crosstalk between the Jak/Stat and Egfr pathways mediates Apc1-driven intestinal stem cell hyperplasia in the Drosophila adult midgut. Development 139(24):4524–4535. doi:10.1242/dev.078261

    Article  CAS  PubMed  Google Scholar 

  68. Tian A, Benchabane H, Wang Z, Ahmed Y (2016) Regulation of stem cell proliferation and cell fate specification by wingless/Wnt signaling gradients enriched at adult intestinal compartment boundaries. PLoS Genet 12(2):e1005822. doi:10.1371/journal.pgen.1005822

    Article  PubMed  PubMed Central  Google Scholar 

  69. Jiang J, Hui CC (2008) Hedgehog signaling in development and cancer. Dev Cell 15(6):801–812. doi:10.1016/j.devcel.2008.11.010

    Article  CAS  PubMed  Google Scholar 

  70. Petrova R, Joyner AL (2014) Roles of Hedgehog signaling in adult organ homeostasis and repair. Development 141(18):3458–3471

    Article  Google Scholar 

  71. Li Z, Guo Y, Han L, Zhang Y, Shi L, Huang X, Lin X (2014) Debra-mediated Ci degradation controls tissue homeostasis in Drosophila adult midgut. Stem cell Rep 2(2):135–144. doi:10.1016/j.stemcr.2013.12.011

    Article  Google Scholar 

  72. Tian A, Jiang J (2015) Hedgehog fuels gut regeneration. Oncotarget 6(25):20750–20751

    Article  PubMed  PubMed Central  Google Scholar 

  73. Ayyaz A, Li H, Jasper H (2015) Haemocytes control stem cell activity in the Drosophila intestine. Nat Cell Biol 17(6):736–748. doi:10.1038/ncb3174

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Houlston R, Bevan S, Williams A, Young J, Dunlop M, Rozen P, Eng C, Markie D, Woodford-Richens K, Rodriguez-Bigas MA, Leggett B, Neale K, Phillips R, Sheridan E, Hodgson S, Iwama T, Eccles D, Bodmer W, Tomlinson I (1998) Mutations in DPC4 (SMAD4) cause juvenile polyposis syndrome, but only account for a minority of cases. Hum Mol Genet 7(12):1907–1912

    Article  CAS  PubMed  Google Scholar 

  75. Howe JR, Roth S, Ringold JC, Summers RW, Jarvinen HJ, Sistonen P, Tomlinson IP, Houlston RS, Bevan S, Mitros FA, Stone EM, Aaltonen LA (1998) Mutations in the SMAD4/DPC4 gene in juvenile polyposis. Science 280(5366):1086–1088

    Article  CAS  PubMed  Google Scholar 

  76. Howe JR, Bair JL, Sayed MG, Anderson ME, Mitros FA, Petersen GM, Velculescu VE, Traverso G, Vogelstein B (2001) Germline mutations of the gene encoding bone morphogenetic protein receptor 1A in juvenile polyposis. Nat Genet 28(2):184–187. doi:10.1038/88919

    Article  CAS  PubMed  Google Scholar 

  77. Zhang L, Yue T, Jiang J (2009) Hippo signaling pathway and organ size control. Fly 3(1):68–73

    Article  PubMed  Google Scholar 

  78. Pan D (2010) The hippo signaling pathway in development and cancer. Dev Cell 19(4):491–505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Ramos A, Camargo FD (2012) The Hippo signaling pathway and stem cell biology. Trends Cell Biol 22(7):339–346. doi:10.1016/j.tcb.2012.04.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Shaw RL, Kohlmaier A, Polesello C, Veelken C, Edgar BA, Tapon N (2010) The Hippo pathway regulates intestinal stem cell proliferation during Drosophila adult midgut regeneration. Development 137(24):4147–4158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Ren F, Shi Q, Chen Y, Jiang A, Ip YT, Jiang H, Jiang J (2013) Drosophila Myc integrates multiple signaling pathways to regulate intestinal stem cell proliferation during midgut regeneration. Cell Res 23(9):1133–1146. doi:10.1038/cr.2013.101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Huang H, Li J, Hu L, Ge L, Ji H, Zhao Y, Zhang L (2014) Bantam is essential for Drosophila intestinal stem cell proliferation in response to Hippo signaling. Dev Biol 385(2):211–219. doi:10.1016/j.ydbio.2013.11.008

    Article  CAS  PubMed  Google Scholar 

  83. Cai J, Zhang N, Zheng Y, de Wilde RF, Maitra A, Pan D (2010) The Hippo signaling pathway restricts the oncogenic potential of an intestinal regeneration program. Genes Dev 24(21):2383–2388

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Sansores-Garcia L, Bossuyt W, Wada K, Yonemura S, Tao C, Sasaki H, Halder G (2011) Modulating F-actin organization induces organ growth by affecting the Hippo pathway. EMBO J 30(12):2325–2335. doi:10.1038/emboj.2011.157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Zhao B, Li L, Wang L, Wang CY, Yu J, Guan KL (2012) Cell detachment activates the Hippo pathway via cytoskeleton reorganization to induce anoikis. Genes Dev 26(1):54–68. doi:10.1101/gad.173435.111

    Article  PubMed  PubMed Central  Google Scholar 

  86. Li Q, Li S, Mana-Capelli S, Roth Flach RJ, Danai LV, Amcheslavsky A, Nie Y, Kaneko S, Yao X, Chen X, Cotton JL, Mao J, McCollum D, Jiang J, Czech MP, Xu L, Ip YT (2014) The conserved misshapen-warts-Yorkie pathway acts in enteroblasts to regulate intestinal stem cells in Drosophila. Dev Cell 31(3):291–304. doi:10.1016/j.devcel.2014.09.012

    Article  PubMed  PubMed Central  Google Scholar 

  87. Meyer N, Penn LZ (2008) Reflecting on 25 years with MYC. Nat Rev Cancer 8(12):976–990. doi:10.1038/nrc2231

    Article  CAS  PubMed  Google Scholar 

  88. Meng FW, Biteau B (2015) A sox transcription factor is a critical regulator of adult stem cell proliferation in the Drosophila Intestine. Cell reports 13(5):906–914. doi:10.1016/j.celrep.2015.09.061

    Article  CAS  PubMed  Google Scholar 

  89. Zhai Z, Kondo S, Ha N, Boquete JP, Brunner M, Ueda R, Lemaitre B (2015) Accumulation of differentiating intestinal stem cell progenies drives tumorigenesis. Nat Commun 6:10219. doi:10.1038/ncomms10219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Jin Y, Ha N, Fores M, Xiang J, Glasser C, Maldera J, Jimenez G, Edgar BA (2015) EGFR/Ras signaling controls Drosophila intestinal stem cell proliferation via capicua-regulated genes. PLoS Genet 11(12):e1005634. doi:10.1371/journal.pgen.1005634

    Article  PubMed  PubMed Central  Google Scholar 

  91. Lin G, Zhang X, Ren J, Pang Z, Wang C, Xu N, Xi R (2013) Integrin signaling is required for maintenance and proliferation of intestinal stem cells in Drosophila. Dev Biol 377(1):177–187. doi:10.1016/j.ydbio.2013.01.032

    Article  CAS  PubMed  Google Scholar 

  92. You J, Zhang Y, Li Z, Lou Z, Jin L, Lin X (2014) Drosophila perlecan regulates intestinal stem cell activity via cell-matrix attachment. Stem Cell Rep 2(6):761–769. doi:10.1016/j.stemcr.2014.04.007

    Article  CAS  Google Scholar 

  93. Amcheslavsky A, Song W, Li Q, Nie Y, Bragatto I, Ferrandon D, Perrimon N, Ip YT (2014) Enteroendocrine cells support intestinal stem-cell-mediated homeostasis in Drosophila. Cell Rep 9(1):32–39. doi:10.1016/j.celrep.2014.08.052

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Deng H, Gerencser AA, Jasper H (2015) Signal integration by Ca(2+) regulates intestinal stem-cell activity. Nature 528(7581):212–217. doi:10.1038/nature16170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Zeng X, Han L, Singh SR, Liu H, Neumuller RA, Yan D, Hu Y, Liu Y, Liu W, Lin X, Hou SX (2015) Genome-wide RNAi screen identifies networks involved in intestinal stem cell regulation in Drosophila. Cell reports 10(7):1226–1238. doi:10.1016/j.celrep.2015.01.051

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work is supported by grants from NIH (GM106188, and GM118063) and Welch Foundation (I-1603) to Jin Jiang (J, J). Huaqi Jiang (H.J) is supported by a grant from NIH (DK102576). JJ is a Eugene McDermott Endowed Scholar in Biomedical Science at UT Southwestern Medical Center.

Author information

Authors and Affiliations

  1. Department of Molecular Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, 75390, USA

    Huaqi Jiang, Aiguo Tian & Jin Jiang

  2. Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, 75390, USA

    Jin Jiang

Authors
  1. Huaqi Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aiguo Tian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jin Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jin Jiang.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jiang, H., Tian, A. & Jiang, J. Intestinal stem cell response to injury: lessons from Drosophila . Cell. Mol. Life Sci. 73, 3337–3349 (2016). https://doi.org/10.1007/s00018-016-2235-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-016-2235-9

Keywords

Search

Navigation