Myc in Stem Cell Behaviour: Insights from Drosophila

  • Leonie M. QuinnEmail author
  • Julie Secombe
  • Gary R. Hime
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 786)


The Myc family proteins are key regulators of animal growth and development, which have critical roles in modulating stem cell behaviour. Since the identification of the oncogenic potential of c-Myc in the early 1980s the mammalian Myc family, which is comprised of c-Myc, N-Myc, and L-Myc, has been studied extensively. dMyc, the only Drosophila member of the Myc gene family, is orthologous to the mammalian c-Myc oncoprotein. Here we discuss key studies addressing the function of the Myc family in stem cell behaviour in both Drosophila Models and mammalian systems.


Myc Drosophila Cell growth Cell cycle Stem cells Cancer 



Thanks to Bob Eisenman and David Stein for the dMyc antibodies and to the Vienna Drosophila Research Centre (VDRC) for the dMyc RNAi lines. This work was supported by grants from the National Health and Medical Research Council (NHMRC).


  1. 1.
    Vennstrom B, Sheiness D, Zabielski J, Bishop JM (1982) Isolation and characterization of c-myc, a cellular homolog of the oncogene (v-myc) of avian myelocytomatosis virus strain 29. J Virol 42(3):773–779PubMedGoogle Scholar
  2. 2.
    Eilers M, Eisenman RN (2008) Myc’s broad reach. Genes Dev 22(20):2755–2766PubMedGoogle Scholar
  3. 3.
    Eisenman RN (2001) Deconstructing myc. Genes Dev 15(16):2023–2030PubMedGoogle Scholar
  4. 4.
    Gallant P, Shiio Y, Cheng PF, Parkhurst SM et al (1996) Myc and Max homologs in Drosophila. Science 274(5292):1523–1527PubMedGoogle Scholar
  5. 5.
    Johnston LA, Prober DA, Edgar BA, Eisenman RN et al (1999) Drosophila myc regulates cellular growth during development. Cell 98(6):779–790PubMedGoogle Scholar
  6. 6.
    Grandori C, Eisenman RN (1997) Myc target genes. Trends Biochem Sci 22(5):177–181PubMedGoogle Scholar
  7. 7.
    Grewal SS, Li L, Orian A, Eisenman RN et al (2005) Myc-dependent regulation of ribosomal RNA synthesis during Drosophila development. Nat Cell Biol 7(3):295–302PubMedGoogle Scholar
  8. 8.
    Orian A, Grewal SS, Knoepfler PS, Edgar BA et al (2005) Genomic binding and transcriptional regulation by the Drosophila Myc and Mnt transcription factors. Cold Spring Harb Symp Quant Biol 70:299–307PubMedGoogle Scholar
  9. 9.
    Gallant P (2006) Myc/Max/Mad in invertebrates: the evolution of the Max network. Curr Top Microbiol Immunol 302:235–253PubMedGoogle Scholar
  10. 10.
    Loo LW, Secombe J, Little JT, Carlos LS et al (2005) The transcriptional repressor dMnt is a regulator of growth in Drosophila melanogaster. Mol Cell Biol 25(16):7078–7091PubMedGoogle Scholar
  11. 11.
    Orian A, van Steensel B, Delrow J, Bussemaker HJ et al (2003) Genomic binding by the Drosophila Myc, Max, Mad/Mnt transcription factor network. Genes Dev 17(9):1101–1114PubMedGoogle Scholar
  12. 12.
    Davis AC, Wims M, Spotts GD, Hann SR et al (1993) A null c-myc mutation causes lethality before 10.5 days of gestation in homozygotes and reduced fertility in heterozygous female mice. Genes Dev 7(4):671–682PubMedGoogle Scholar
  13. 13.
    Trumpp A, Refaeli Y, Oskarsson T, Gasser S et al (2001) c-Myc regulates mammalian body size by controlling cell number but not cell size. Nature 414(6865):768–773PubMedGoogle Scholar
  14. 14.
    Dubois NC, Adolphe C, Ehninger A, Wang RA et al (2008) Placental rescue reveals a sole requirement for c-Myc in embryonic erythroblast survival and hematopoietic stem cell function. Development 135(14):2455–2465PubMedGoogle Scholar
  15. 15.
    Bouchard C, Staller P, Eilers M (1998) Control of cell proliferation by Myc. Trends Cell Biol 8(5):202–206PubMedGoogle Scholar
  16. 16.
    Schmidt EV (1999) The role of c-myc in cellular growth control. Oncogene 18(19):2988–2996PubMedGoogle Scholar
  17. 17.
    Schmidt EV (2004) The role of c-myc in regulation of translation initiation. Oncogene 23(18):3217–3221PubMedGoogle Scholar
  18. 18.
    Dang CV (1999) c-Myc target genes involved in cell growth, apoptosis, and metabolism. Mol Cell Biol 19(1):1–11PubMedGoogle Scholar
  19. 19.
    Jamerson MH, Johnson MD, Dickson RB (2004) Of mice and Myc: c-Myc and mammary tumorigenesis. J Mammary Gland Biol Neoplasia 9(1):27–37PubMedGoogle Scholar
  20. 20.
    Lee LA, Dang CV (2006) Myc target transcriptomes. Curr Top Microbiol Immunol 302:145–167PubMedGoogle Scholar
  21. 21.
    Liao DJ, Dickson RB (2000) c-Myc in breast cancer. Endocr Relat Cancer 7(3):143–164PubMedGoogle Scholar
  22. 22.
    Schreiber-Agus N, Stein D, Chen K, Goltz JS et al (1997) Drosophila Myc is oncogenic in mammalian cells and plays a role in the diminutive phenotype. Proc Natl Acad Sci USA 94(4):1235–1240PubMedGoogle Scholar
  23. 23.
    Benassayag C, Montero L, Colombie N, Gallant P et al (2005) Human c-Myc isoforms differentially regulate cell growth and apoptosis in Drosophila melanogaster. Mol Cell Biol 25(22):9897–9909PubMedGoogle Scholar
  24. 24.
    Coller HA, Grandori C, Tamayo P, Colbert T et al (2000) Expression analysis with oligonucleotide microarrays reveals that MYC regulates genes involved in growth, cell cycle, signaling, and adhesion. Proc Natl Acad Sci USA 97(7):3260–3265PubMedGoogle Scholar
  25. 25.
    Grandori C, Cowley SM, James LP, Eisenman RN (2000) The Myc/Max/Mad network and the transcriptional control of cell behavior. Annu Rev Cell Dev Biol 16:653–699PubMedGoogle Scholar
  26. 26.
    Grandori C, Gomez-Roman N, Felton-Edkins ZA, Ngouenet C et al (2005) c-Myc binds to human ribosomal DNA and stimulates transcription of rRNA genes by RNA polymerase I. Nat Cell Biol 7(3):311–318PubMedGoogle Scholar
  27. 27.
    Levens D (2002) Disentangling the MYC web. Proc Natl Acad Sci USA 99(9):5757–5759PubMedGoogle Scholar
  28. 28.
    Liu J, Levens D (2006) Making myc. Curr Top Microbiol Immunol 302:1–32PubMedGoogle Scholar
  29. 29.
    Levens D (2010) You don’t muck with MYC. Genes Cancer 1(6):547–554PubMedGoogle Scholar
  30. 30.
    Ruggero D (2009) The role of Myc-induced protein synthesis in cancer. Cancer Res 69(23):8839–8843PubMedGoogle Scholar
  31. 31.
    Pierce SB, Yost C, Anderson SA, Flynn EM et al (2008) Drosophila growth and development in the absence of dMyc and dMnt. Dev Biol 315(2):303–316PubMedGoogle Scholar
  32. 32.
    Poortinga G, Hannan KM, Snelling H, Walkley CR et al (2004) MAD1 and c-MYC regulate UBF and rDNA transcription during granulocyte differentiation. EMBO J 23(16):3325–3335PubMedGoogle Scholar
  33. 33.
    Poortinga G, Wall M, Sanij E, Siwicki K et al (2011) c-MYC coordinately regulates ribosomal gene chromatin remodeling and Pol I availability during granulocyte differentiation. Nucleic Acids Res 39(8):3267–3281PubMedGoogle Scholar
  34. 34.
    Gomez-Roman N, Felton-Edkins ZA, Kenneth NS, Goodfellow SJ et al (2006) Activation by c-Myc of transcription by RNA polymerases I, II and III. Biochem Soc Symp 73:141–154PubMedGoogle Scholar
  35. 35.
    Gomez-Roman N, Grandori C, Eisenman RN, White RJ (2003) Direct activation of RNA polymerase III transcription by c-Myc. Nature 421(6920):290–294PubMedGoogle Scholar
  36. 36.
    Oskarsson T, Trumpp A (2005) The Myc trilogy: lord of RNA polymerases. Nat Cell Biol 7(3):215–217PubMedGoogle Scholar
  37. 37.
    Steiger D, Furrer M, Schwinkendorf D, Gallant P (2008) Max-independent functions of Myc in Drosophila melanogaster. Nat Genet 40(9):1084–1091PubMedGoogle Scholar
  38. 38.
    Cowling VH, D’Cruz CM, Chodosh LA, Cole MD (2007) c-Myc transforms human mammary epithelial cells through repression of the Wnt inhibitors DKK1 and SFRP1. Mol Cell Biol 27(14):5135–5146PubMedGoogle Scholar
  39. 39.
    Morrish F, Neretti N, Sedivy JM, Hockenbery DM (2008) The oncogene c-Myc coordinates regulation of metabolic networks to enable rapid cell cycle entry. Cell Cycle 7(8):1054–1066PubMedGoogle Scholar
  40. 40.
    Zhang H, Gao P, Fukuda R, Kumar G et al (2007) HIF-1 inhibits mitochondrial biogenesis and cellular respiration in VHL-deficient renal cell carcinoma by repression of C-MYC activity. Cancer Cell 11(5):407–420PubMedGoogle Scholar
  41. 41.
    Teleman AA, Hietakangas V, Sayadian AC, Cohen SM (2008) Nutritional control of protein biosynthetic capacity by insulin via Myc in Drosophila. Cell Metab 7(1):21–32PubMedGoogle Scholar
  42. 42.
    Duman-Scheel M, Johnston LA, Du W (2004) Repression of dMyc expression by Wingless promotes Rbf-induced G1 arrest in the presumptive Drosophila wing margin. Proc Natl Acad Sci USA 101(11):3857–3862PubMedGoogle Scholar
  43. 43.
    Maines JZ, Stevens LM, Tong X, Stein D (2004) Drosophila dMyc is required for ovary cell growth and endoreplication. Development 131(4):775–786PubMedGoogle Scholar
  44. 44.
    Pierce SB, Yost C, Britton JS, Loo LW et al (2004) dMyc is required for larval growth and endoreplication in Drosophila. Development 131(10):2317–2327PubMedGoogle Scholar
  45. 45.
    Wu DC, Johnston LA (2010) Control of wing size and proportions by Drosophila myc. Genetics 184(1):199–211PubMedGoogle Scholar
  46. 46.
    Giacinti C, Giordano A (2006) RB and cell cycle progression. Oncogene 25(38):5220–5227PubMedGoogle Scholar
  47. 47.
    Hooker CW, Hurlin PJ (2006) Of Myc and Mnt. J Cell Sci 119(Pt 2):208–216PubMedGoogle Scholar
  48. 48.
    Hurlin PJ, Huang J (2006) The MAX-interacting transcription factor network. Semin Cancer Biol 16(4):265–274PubMedGoogle Scholar
  49. 49.
    Dominguez-Sola D, Ying CY, Grandori C, Ruggiero L et al (2007) Non-transcriptional control of DNA replication by c-Myc. Nature 448(7152):445–451PubMedGoogle Scholar
  50. 50.
    Ohlstein B, Spradling A (2006) The adult Drosophila posterior midgut is maintained by pluripotent stem cells. Nature 439(7075):470–474PubMedGoogle Scholar
  51. 51.
    Takashima S, Mkrtchyan M, Younossi-Hartenstein A, Merriam JR et al (2008) The behaviour of Drosophila adult hindgut stem cells is controlled by Wnt and Hh signalling. Nature 454(7204):651–655PubMedGoogle Scholar
  52. 52.
    Singh SR, Liu W, Hou SX (2007) The adult Drosophila Malpighian tubules are maintained by multipotent stem cells. Cell Stem Cell 1(2):191–203PubMedGoogle Scholar
  53. 53.
    Betschinger J, Mechtler K, Knoblich JA (2006) Asymmetric segregation of the tumor suppressor brat regulates self-renewal in Drosophila neural stem cells. Cell 124(6):1241–1253PubMedGoogle Scholar
  54. 54.
    Krzemien J, Dubois L, Makki R, Meister M et al (2007) Control of blood cell homeostasis in Drosophila larvae by the posterior signalling centre. Nature 446(7133):325–328PubMedGoogle Scholar
  55. 55.
    Mandal L, Martinez-Agosto JA, Evans CJ, Hartenstein V et al (2007) A Hedgehog- and Antennapedia-dependent niche maintains Drosophila haematopoietic precursors. Nature 446(7133):320–324PubMedGoogle Scholar
  56. 56.
    Fuller MT, Spradling AC (2007) Male and female Drosophila germline stem cells: two versions of immortality. Science 316(5823):402–404PubMedGoogle Scholar
  57. 57.
    Spradling AC, Zheng Y (2007) Developmental biology. The mother of all stem cells? Science 315(5811):469–470PubMedGoogle Scholar
  58. 58.
    Xie T, Spradling AC (2000) A niche maintaining germ line stem cells in the Drosophila ovary. Science 290(5490):328–330PubMedGoogle Scholar
  59. 59.
    Neumüller RA, Betschinger J, Fischer A, Bushati N et al (2008) Mei-P26 regulates microRNAs and cell growth in the Drosophila ovarian stem cell lineage. Nature 454(7201):241–245PubMedGoogle Scholar
  60. 60.
    Siddall NA, Lin JI, Hime GR, Quinn LM (2009) Myc–what we have learned from flies. Curr Drug Targets 10(7):590–601PubMedGoogle Scholar
  61. 61.
    Page SL, McKim KS, Deneen B, Van Hook TL et al (2000) Genetic studies of mei-P26 reveal a link between the processes that control germ cell proliferation in both sexes and those that control meiotic exchange in Drosophila. Genetics 155(4):1757–1772PubMedGoogle Scholar
  62. 62.
    Ohlstein B, McKearin D (1997) Ectopic expression of the Drosophila Bam protein eliminates oogenic germline stem cells. Development 124(18):3651–3662PubMedGoogle Scholar
  63. 63.
    Schwamborn JC, Berezikov E, Knoblich JA (2009) The TRIM-NHL protein TRIM32 activates microRNAs and prevents self-renewal in mouse neural progenitors. Cell 136(5):913–925PubMedGoogle Scholar
  64. 64.
    Herranz H, Hong X, Perez L, Ferreira A et al (2010) The miRNA machinery targets Mei-P26 and regulates Myc protein levels in the Drosophila wing. EMBO J 29(10):1688–1698PubMedGoogle Scholar
  65. 65.
    Harris RE, Pargett M, Sutcliffe C, Umulis D et al (2011) Brat promotes stem cell differentiation via control of a bistable switch that restricts BMP signaling. Dev Cell 20(1):72–83PubMedGoogle Scholar
  66. 66.
    Jin Z, Kirilly D, Weng C, Kawase E et al (2008) Differentiation-defective stem cells outcompete normal stem cells for niche occupancy in the Drosophila ovary. Cell Stem Cell 2(1):39–49PubMedGoogle Scholar
  67. 67.
    Braydich-Stolle L, Kostereva N, Dym M, Hofmann MC (2007) Role of Src family kinases and N-Myc in spermatogonial stem cell proliferation. Dev Biol 304(1):34–45PubMedGoogle Scholar
  68. 68.
    Laurenti E, Varnum-Finney B, Wilson A, Ferrero I et al (2008) Hematopoietic stem cell function and survival depend on c-Myc and N-Myc activity. Cell Stem Cell 3(6):611–624PubMedGoogle Scholar
  69. 69.
    Wilson A, Murphy MJ, Oskarsson T, Kaloulis K et al (2004) c-Myc controls the balance between hematopoietic stem cell self-renewal and differentiation. Genes Dev 18(22):2747–2763PubMedGoogle Scholar
  70. 70.
    Baena E, Ortiz M, Martinez AC, de Alboran IM (2007) c-Myc is essential for hematopoietic stem cell differentiation and regulates Lin(-)Sca-1(+)c-Kit(-) cell generation through p21. Exp Hematol 35(9):1333–1343PubMedGoogle Scholar
  71. 71.
    Crozatier M, Meister M (2007) Drosophila haematopoiesis. Cell Microbiol 9(5):1117–1126PubMedGoogle Scholar
  72. 72.
    Blanpain C, Fuchs E (2006) Epidermal stem cells of the skin. Annu Rev Cell Dev Biol 22:339–373PubMedGoogle Scholar
  73. 73.
    Gandarillas A, Watt FM (1997) c-Myc promotes differentiation of human epidermal stem cells. Genes Dev 11(21):2869–2882PubMedGoogle Scholar
  74. 74.
    Arnold I, Watt FM (2001) c-Myc activation in transgenic mouse epidermis results in mobilization of stem cells and differentiation of their progeny. Curr Biol 11(8):558–568PubMedGoogle Scholar
  75. 75.
    Waikel RL, Kawachi Y, Waikel PA, Wang XJ et al (2001) Deregulated expression of c-Myc depletes epidermal stem cells. Nat Genet 28(2):165–168PubMedGoogle Scholar
  76. 76.
    Frye M, Gardner C, Li ER, Arnold I et al (2003) Evidence that Myc activation depletes the epidermal stem cell compartment by modulating adhesive interactions with the local microenvironment. Development 130(12):2793–2808PubMedGoogle Scholar
  77. 77.
    Zanet J, Pibre S, Jacquet C, Ramirez A et al (2005) Endogenous Myc controls mammalian epidermal cell size, hyperproliferation, endoreplication and stem cell amplification. J Cell Sci 118(Pt 8):1693–1704PubMedGoogle Scholar
  78. 78.
    Frye M, Fisher AG, Watt FM (2007) Epidermal stem cells are defined by global histone modifications that are altered by Myc-induced differentiation. PLoS One 2(8):e763PubMedGoogle Scholar
  79. 79.
    Bettess MD, Dubois N, Murphy MJ, Dubey C et al (2005) c-Myc is required for the formation of intestinal crypts but dispensable for homeostasis of the adult intestinal epithelium. Mol Cell Biol 25(17):7868–7878PubMedGoogle Scholar
  80. 80.
    Muncan V, Sansom OJ, Tertoolen L, Phesse TJ et al (2006) Rapid loss of intestinal crypts upon conditional deletion of the Wnt/Tcf-4 target gene c-Myc. Mol Cell Biol 26(22):8418–8426PubMedGoogle Scholar
  81. 81.
    He TC, Sparks AB, Rago C, Hermeking H et al (1998) Identification of c-MYC as a target of the APC pathway. Science 281(5382):1509–1512PubMedGoogle Scholar
  82. 82.
    Sansom OJ, Meniel VS, Muncan V, Phesse TJ et al (2007) Myc deletion rescues Apc deficiency in the small intestine. Nature 446(7136):676–679PubMedGoogle Scholar
  83. 83.
    van de Wetering M, Sancho E, Verweij C, de Lau W et al (2002) The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell 111(2):241–250PubMedGoogle Scholar
  84. 84.
    Wilkins JA, Sansom OJ (2008) C-Myc is a critical mediator of the phenotypes of Apc loss in the intestine. Cancer Res 68(13):4963–4966PubMedGoogle Scholar
  85. 85.
    Klaus A, Birchmeier W (2008) Wnt signalling and its impact on development and cancer. Nat Rev Cancer 8(5):387–398PubMedGoogle Scholar
  86. 86.
    Korinek V, Barker N, Morin PJ, van Wichen D et al (1997) Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma. Science 275(5307):1784–1787PubMedGoogle Scholar
  87. 87.
    Morin PJ, Sparks AB, Korinek V, Barker N et al (1997) Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science 275(5307):1787–1790PubMedGoogle Scholar
  88. 88.
    Sansom OJ, Reed KR, Hayes AJ, Ireland H et al (2004) Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration. Genes Dev 18(12):1385–1390PubMedGoogle Scholar
  89. 89.
    Kinzler KW, Nilbert MC, Su LK, Vogelstein B et al (1991) Identification of FAP locus genes from chromosome 5q21. Science 253(5020):661–665PubMedGoogle Scholar
  90. 90.
    Athineos D, Sansom OJ (2010) Myc heterozygosity attenuates the phenotypes of APC deficiency in the small intestine. Oncogene 29(17):2585–2590PubMedGoogle Scholar
  91. 91.
    Finch AJ, Soucek L, Junttila MR, Swigart LB et al (2009) Acute overexpression of Myc in intestinal epithelium recapitulates some but not all the changes elicited by Wnt/beta-catenin pathway activation. Mol Cell Biol 29(19):5306–5315PubMedGoogle Scholar
  92. 92.
    Reed KR, Athineos D, Meniel VS, Wilkins JA et al (2008) B-catenin deficiency, but not Myc deletion, suppresses the immediate phenotypes of APC loss in the liver. Proc Natl Acad Sci USA 105(48):18919–18923PubMedGoogle Scholar
  93. 93.
    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):695–710PubMedGoogle Scholar
  94. 94.
    Evans MJ, Kaufman MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292(5819):154–156PubMedGoogle Scholar
  95. 95.
    Martin GR (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci USA 78(12):7634–7638PubMedGoogle Scholar
  96. 96.
    Cartwright P, McLean C, Sheppard A, Rivett D et al (2005) LIF/STAT3 controls ES cell self-renewal and pluripotency by a Myc-dependent mechanism. Development 132(5):885–896PubMedGoogle Scholar
  97. 97.
    Wilmut I, Schnieke AE, McWhir J, Kind AJ et al (1997) Viable offspring derived from fetal and adult mammalian cells. Nature 385(6619):810–813PubMedGoogle Scholar
  98. 98.
    Tada M, Takahama Y, Abe K, Nakatsuji N et al (2001) Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells. Curr Biol 11(19):1553–1558PubMedGoogle Scholar
  99. 99.
    Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4):663–676PubMedGoogle Scholar
  100. 100.
    Okita K, Ichisaka T, Yamanaka S (2007) Generation of germline-competent induced pluripotent stem cells. Nature 448(7151):313–317PubMedGoogle Scholar
  101. 101.
    Nakagawa M, Koyanagi M, Tanabe K, Takahashi K et al (2008) Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol 26(1):101–106PubMedGoogle Scholar
  102. 102.
    Aoki T, Ohnishi H, Oda Y, Tadokoro M et al (2010) Generation of induced pluripotent stem cells from human adipose-derived stem cells without c-MYC. Tissue Eng Part A 16(7):2197–2206PubMedGoogle Scholar
  103. 103.
    Jincho Y, Araki R, Hoki Y, Tamura C et al (2010) Generation of genome integration-free induced pluripotent stem cells from fibroblasts of C57BL/6 mice without c-Myc transduction. J Biol Chem 285(34):26384–26389PubMedGoogle Scholar
  104. 104.
    Araki R, Hoki Y, Uda M, Nakamura M et al (2011) Crucial role of c-Myc in the generation of induced pluripotent stem cells. Stem Cells 29(9):1362–1370PubMedGoogle Scholar
  105. 105.
    Takayama N, Nishimura S, Nakamura S, Shimizu T et al (2010) Transient activation of c-MYC expression is critical for efficient platelet generation from human induced pluripotent stem cells. J Exp Med 207(13):2817–2830PubMedGoogle Scholar
  106. 106.
    Smith KN, Singh AM, Dalton S (2010) Myc represses primitive endoderm differentiation in pluripotent stem cells. Cell Stem Cell 7(3):343–354PubMedGoogle Scholar
  107. 107.
    Lin CH, Jackson AL, Guo J, Linsley PS et al (2009) Myc-regulated microRNAs attenuate embryonic stem cell differentiation. EMBO J 28(20):3157–3170PubMedGoogle Scholar
  108. 108.
    Varlakhanova N, Cotterman R, Bradnam K, Korf I et al (2011) Myc and Miz-1 have coordinate genomic functions including targeting Hox genes in human embryonic stem cells. Epigenetics Chromatin 4:20PubMedGoogle Scholar
  109. 109.
    Baker NE, Li W (2008) Cell competition and its possible relation to cancer. Cancer Res 68(14):5505–5507PubMedGoogle Scholar
  110. 110.
    de la Cova C, Abril M, Bellosta P, Gallant P et al (2004) Drosophila myc regulates organ size by inducing cell competition. Cell 117(1):107–116PubMedGoogle Scholar
  111. 111.
    Moreno E, Basler K (2004) dMyc transforms cells into super-competitors. Cell 117(1):117–129PubMedGoogle Scholar
  112. 112.
    Senoo-Matsuda N, Johnston LA (2007) Soluble factors mediate competitive and cooperative interactions between cells expressing different levels of Drosophila Myc. Proc Natl Acad Sci USA 104(47):18543–18548PubMedGoogle Scholar
  113. 113.
    Li W, Baker NE (2007) Engulfment is required for cell competition. Cell 129(6):1215–1225PubMedGoogle Scholar
  114. 114.
    Rhiner C, Diaz B, Portela M, Poyatos JF et al (2009) Persistent competition among stem cells and their daughters in the Drosophila ovary germline niche. Development 136(6):995–1006PubMedGoogle Scholar
  115. 115.
    Kohl NE, Kanda N, Schreck RR, Bruns G et al (1983) Transposition and amplification of oncogene-related sequences in human neuroblastomas. Cell 35(2 Pt 1):359–367PubMedGoogle Scholar
  116. 116.
    Schwab M, Alitalo K, Klempnauer KH, Varmus HE et al (1983) Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumour. Nature 305(5931):245–248PubMedGoogle Scholar
  117. 117.
    Jakobovits A, Schwab M, Bishop JM, Martin GR (1985) Expression of N-myc in teratocarcinoma stem cells and mouse embryos. Nature 318(6042):188–191PubMedGoogle Scholar
  118. 118.
    Knoepfler PS, Cheng PF, Eisenman RN (2002) N-myc is essential during neurogenesis for the rapid expansion of progenitor cell populations and the inhibition of neuronal differentiation. Genes Dev 16(20):2699–2712PubMedGoogle Scholar
  119. 119.
    Nagao M, Campbell K, Burns K, Kuan CY et al (2008) Coordinated control of self-renewal and differentiation of neural stem cells by Myc and the p19ARF-p53 pathway. J Cell Biol 183(7):1243–1257PubMedGoogle Scholar
  120. 120.
    Wang J, Wang H, Li Z, Wu Q et al (2008) c-Myc is required for maintenance of glioma cancer stem cells. PLoS One 3(11):e3769PubMedGoogle Scholar
  121. 121.
    Zheng H, Ying H, Yan H, Kimmelman AC et al (2008) Pten and p53 converge on c-Myc to control differentiation, self-renewal, and transformation of normal and neoplastic stem cells in glioblastoma. Cold Spring Harb Symp Quant Biol 73:427–437PubMedGoogle Scholar
  122. 122.
    Liu C, Zong H (2012) Developmental origins of brain tumors. Curr Opin Neurobiol 22(5):844–849PubMedGoogle Scholar
  123. 123.
    Su X, Gopalakrishnan V, Stearns D, Aldape K et al (2006) Abnormal expression of REST/NRSF and Myc in neural stem/progenitor cells causes cerebellar tumors by blocking neuronal differentiation. Mol Cell Biol 26(5):1666–1678PubMedGoogle Scholar
  124. 124.
    Harrison SM, Harrison DA (2006) Contrasting mechanisms of stem cell maintenance in Drosophila. Semin Cell Dev Biol 17(4):518–533PubMedGoogle Scholar
  125. 125.
    Ponzielli R, Katz S, Barsyte-Lovejoy D, Penn LZ (2005) Cancer therapeutics: targeting the dark side of Myc. Eur J Cancer 41(16):2485–2501PubMedGoogle Scholar
  126. 126.
    Iorio MV, Croce CM (2012) microRNA involvement in human cancer. Carcinogenesis 33(6):1126–1133PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Leonie M. Quinn
    • 1
    Email author
  • Julie Secombe
    • 2
  • Gary R. Hime
    • 1
  1. 1.Department of Anatomy and NeuroscienceUniversity of MelbourneParkville, MelbourneAustralia
  2. 2.Department of GeneticsAlbert Einstein College of MedicineBronx, New YorkUSA

Personalised recommendations