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Cellular and Molecular Life Sciences

, Volume 73, Issue 17, pp 3337–3349 | Cite as

Intestinal stem cell response to injury: lessons from Drosophila

Review

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.

Keywords

ISC midgut Wnt Wg Hedgehog Hh BMP Dpp Gbb EGFR Ras Hippo Yki Yap JAK-STAT JNK Notch Insulin InR Calcium microRNA Aging Tissue damage Self-renewal Symmetric division Asymmetric division Proliferation Regeneration Tumor 

Notes

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.

References

  1. 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 CrossRefPubMedGoogle Scholar
  2. 2.
    Ohlstein B, Spradling A (2006) The adult Drosophila posterior midgut is maintained by pluripotent stem cells. Nature 439(7075):470–474CrossRefPubMedGoogle Scholar
  3. 3.
    Micchelli CA, Perrimon N (2006) Evidence that stem cells reside in the adult Drosophila midgut epithelium. Nature 439(7075):475–479CrossRefPubMedGoogle Scholar
  4. 4.
    Jiang H, Edgar BA (2009) EGFR signaling regulates the proliferation of Drosophila adult midgut progenitors. Development 136(3):483–493CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Mathur D, Bost A, Driver I, Ohlstein B (2010) A transient niche regulates the specification of Drosophila intestinal stem cells. Science 327(5962):210–213CrossRefPubMedPubMedCentralGoogle Scholar
  6. 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):12–21PubMedGoogle Scholar
  7. 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):161–172CrossRefPubMedGoogle Scholar
  8. 8.
    Ohlstein B, Spradling A (2007) Multipotent Drosophila intestinal stem cells specify daughter cell fates by differential notch signaling. Science 315(5814):988–992CrossRefPubMedGoogle Scholar
  9. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 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):1343–1355CrossRefPubMedPubMedCentralGoogle Scholar
  14. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Amcheslavsky A, Jiang J, Ip YT (2009) Tissue damage-induced intestinal stem cell division in Drosophila. Cell Stem Cell 4(1):49–61CrossRefPubMedPubMedCentralGoogle Scholar
  16. 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):200–211CrossRefPubMedGoogle Scholar
  17. 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 PubMedPubMedCentralGoogle Scholar
  18. 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):442–455CrossRefPubMedPubMedCentralGoogle Scholar
  19. 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):2333–2344CrossRefPubMedPubMedCentralGoogle Scholar
  20. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 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 CrossRefPubMedGoogle Scholar
  23. 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):705–714CrossRefPubMedPubMedCentralGoogle Scholar
  24. 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 CrossRefPubMedGoogle Scholar
  25. 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):695–710CrossRefPubMedPubMedCentralGoogle Scholar
  26. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  27. 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 CrossRefPubMedGoogle Scholar
  28. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 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. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 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 CrossRefPubMedGoogle Scholar
  35. 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):964–968CrossRefPubMedGoogle Scholar
  36. 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):959–963CrossRefPubMedGoogle Scholar
  37. 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 CrossRefPubMedGoogle Scholar
  38. 38.
    Marianes A, Spradling AC (2013) Physiological and stem cell compartmentalization within the Drosophila midgut. Elife 2:e00886. doi: 10.7554/eLife.00886 CrossRefPubMedPubMedCentralGoogle Scholar
  39. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  40. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  41. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 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 CrossRefPubMedGoogle Scholar
  43. 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):903–912CrossRefPubMedGoogle Scholar
  44. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  45. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  46. 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) CrossRefPubMedGoogle Scholar
  47. 47.
    Biteau B, Jasper H (2011) EGF signaling regulates the proliferation of intestinal stem cells in Drosophila. Development 138(6):1045–1055CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Buchon N, Broderick NA, Kuraishi T, Lemaitre B (2010) Drosophila EGFR pathway coordinates stem cell proliferation and gut remodeling following infection. BMC Biol 8:152CrossRefPubMedPubMedCentralGoogle Scholar
  49. 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):84–95CrossRefPubMedGoogle Scholar
  50. 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 354:31–43CrossRefPubMedGoogle Scholar
  51. 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):992–999PubMedPubMedCentralGoogle Scholar
  52. 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):28–37CrossRefPubMedGoogle Scholar
  53. 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 CrossRefPubMedGoogle Scholar
  54. 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):37–49CrossRefPubMedGoogle Scholar
  55. 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):340–343CrossRefPubMedPubMedCentralGoogle Scholar
  56. 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 CrossRefPubMedGoogle Scholar
  57. 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 CrossRefPubMedGoogle Scholar
  58. 58.
    Lee WC, Beebe K, Sudmeier L, Micchelli CA (2009) Adenomatous polyposis coli regulates Drosophila intestinal stem cell proliferation. Development 136(13):2255–2264CrossRefPubMedGoogle Scholar
  59. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  60. 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 CrossRefPubMedGoogle Scholar
  61. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  62. 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):21064–21069CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Staley BK, Irvine KD (2010) Warts and Yorkie mediate intestinal regeneration by influencing stem cell proliferation. Curr Biol CB 20(17):1580–1587CrossRefPubMedGoogle Scholar
  64. 64.
    Karpowicz P, Perez J, Perrimon N (2010) The Hippo tumor suppressor pathway regulates intestinal stem cell regeneration. Development 137(24):4135–4145CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    van der Flier LG, Clevers H (2009) Stem cells, self-renewal, and differentiation in the intestinal epithelium. Annu Rev Physiol 71:241–260CrossRefPubMedGoogle Scholar
  66. 66.
    Lin G, Xu N, Xi R (2008) Paracrine Wingless signalling controls self-renewal of Drosophila intestinal stem cells. Nature 455(7216):1119–1123CrossRefPubMedGoogle Scholar
  67. 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 CrossRefPubMedGoogle Scholar
  68. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  69. 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 CrossRefPubMedGoogle Scholar
  70. 70.
    Petrova R, Joyner AL (2014) Roles of Hedgehog signaling in adult organ homeostasis and repair. Development 141(18):3458–3471CrossRefGoogle Scholar
  71. 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 CrossRefGoogle Scholar
  72. 72.
    Tian A, Jiang J (2015) Hedgehog fuels gut regeneration. Oncotarget 6(25):20750–20751CrossRefPubMedPubMedCentralGoogle Scholar
  73. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  74. 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):1907–1912CrossRefPubMedGoogle Scholar
  75. 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):1086–1088CrossRefPubMedGoogle Scholar
  76. 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 CrossRefPubMedGoogle Scholar
  77. 77.
    Zhang L, Yue T, Jiang J (2009) Hippo signaling pathway and organ size control. Fly 3(1):68–73CrossRefPubMedGoogle Scholar
  78. 78.
    Pan D (2010) The hippo signaling pathway in development and cancer. Dev Cell 19(4):491–505CrossRefPubMedPubMedCentralGoogle Scholar
  79. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  80. 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):4147–4158CrossRefPubMedPubMedCentralGoogle Scholar
  81. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  82. 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 CrossRefPubMedGoogle Scholar
  83. 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):2383–2388CrossRefPubMedPubMedCentralGoogle Scholar
  84. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  85. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  86. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Meyer N, Penn LZ (2008) Reflecting on 25 years with MYC. Nat Rev Cancer 8(12):976–990. doi: 10.1038/nrc2231 CrossRefPubMedGoogle Scholar
  88. 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 CrossRefPubMedGoogle Scholar
  89. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  90. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  91. 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 CrossRefPubMedGoogle Scholar
  92. 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 CrossRefGoogle Scholar
  93. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  94. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  95. 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 CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer International Publishing 2016

Authors and Affiliations

  1. 1.Department of Molecular BiologyUniversity of Texas Southwestern Medical Center at DallasDallasUSA
  2. 2.Department of PharmacologyUniversity of Texas Southwestern Medical Center at DallasDallasUSA

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