Tissue growth and regeneration are autonomous, stem-cell-mediated processes in which stem cells within the organ self-renew and differentiate to create new cells, leading to new tissue. The processes of growth and regeneration require communication and interplay between neighboring cells. In particular, cell competition, which is a process in which viable cells are actively eliminated by more competitive cells, has been increasingly implicated to play an important role. Here, we discuss the existing literature regarding the current landscape of cell competition, including classical pathways and models, fitness fingerprint mechanisms, and immune system mechanisms of cell competition. We further discuss the clinical relevance of cell competition in the physiological processes of tissue growth and regeneration, highlighting studies in clinically important disease models, including oncological, neurological, and cardiovascular diseases.


Article metrics loading...

Loading full text...

Full text loading...


Literature Cited

  1. Abrams JM. 1.  2002. Competition and compensation: coupled to death in development and cancer. Cell 110:403–6 [Google Scholar]
  2. Baena-Lopez LA, Nojima H, Vincent JP. 2.  2012. Integration of morphogen signalling within the growth regulatory network. Curr. Opin. Cell Biol. 24:166–72 [Google Scholar]
  3. Beck CW, Christen B, Slack JM. 3.  2003. Molecular pathways needed for regeneration of spinal cord and muscle in a vertebrate. Dev. Cell 5:429–39 [Google Scholar]
  4. Bergamaschi A, Tagliabue E, Sorlie T, Naume B, Triulzi T. 4.  et al. 2008. Extracellular matrix signature identifies breast cancer subgroups with different clinical outcome. J. Pathol. 214:357–67 [Google Scholar]
  5. Bhoopathi P, Gondi CS, Gujrati M, Dinh DH, Lakka SS. 5.  2011. SPARC mediates Src-induced disruption of actin cytoskeleton via inactivation of small GTPases Rho-Rac-Cdc42. Cell Signal. 23:1978–87 [Google Scholar]
  6. Bjornson CR, Cheung TH, Liu L, Tripathi PV, Steeper KM, Rando TA. 6.  2012. Notch signaling is necessary to maintain quiescence in adult muscle stem cells. Stem Cells 30:232–42 [Google Scholar]
  7. Bondar T, Medzhitov R. 7.  2010. p53-Mediated hematopoietic stem and progenitor cell competition. Cell Stem Cell 6:309–22 [Google Scholar]
  8. Borowiak M, Garratt AN, Wustefeld T, Strehle M, Trautwein C, Birchmeier C. 8.  2004. Met provides essential signals for liver regeneration. PNAS 101:10608–13 [Google Scholar]
  9. Brack AS, Conboy MJ, Roy S, Lee M, Kuo CJ. 9.  et al. 2007. Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis. Science 317:807–10 [Google Scholar]
  10. Bradke F, Fawcett JW, Spira ME. 10.  2012. Assembly of a new growth cone after axotomy: the precursor to axon regeneration. Nat. Rev. Neurosci. 13:183–93 [Google Scholar]
  11. Bradshaw AD. 11.  2012. Diverse biological functions of the SPARC family of proteins. Int. J. Biochem. Cell Biol. 44:480–88 [Google Scholar]
  12. Brawley C, Matunis E. 12.  2004. Regeneration of male germline stem cells by spermatogonial dedifferentiation in vivo. Science 304:1331–34 [Google Scholar]
  13. Brumby AM, Richardson HE. 13.  2003. scribble mutants cooperate with oncogenic Ras or Notch to cause neoplastic overgrowth in Drosophila. EMBO J. 22:5769–79 [Google Scholar]
  14. Cai J, Zhang N, Zheng Y, de Wilde RF, Maitra A, Pan D. 14.  2010. The Hippo signaling pathway restricts the oncogenic potential of an intestinal regeneration program. Genes Dev. 24:2383–88 [Google Scholar]
  15. Camargo FD, Gokhale S, Johnnidis JB, Fu D, Bell GW. 15.  et al. 2007. YAP1 increases organ size and expands undifferentiated progenitor cells. Curr. Biol. 17:2054–60 [Google Scholar]
  16. Carter M, Chen X, Slowinska B, Minnerath S, Glickstein S. 16.  et al. 2005. Crooked tail (Cd) model of human folate-responsive neural tube defects is mutated in Wnt coreceptor lipoprotein receptor-related protein 6. PNAS 102:12843–48 [Google Scholar]
  17. Chen CL, Schroeder MC, Kango-Singh M, Tao C, Halder G. 17.  2012. Tumor suppression by cell competition through regulation of the Hippo pathway. PNAS 109:484–89 [Google Scholar]
  18. Chera S, Ghila L, Dobretz K, Wenger Y, Bauer C. 18.  et al. 2009. Apoptotic cells provide an unexpected source of Wnt3 signaling to drive hydra head regeneration. Dev. Cell 17:279–89 [Google Scholar]
  19. Chin D, Boyle GM, Williams RM, Ferguson K, Pandeya N. 19.  et al. 2005. Novel markers for poor prognosis in head and neck cancer. Int. J. Cancer 113:789–97 [Google Scholar]
  20. Chlenski A, Cohn SL. 20.  2010. Modulation of matrix remodeling by SPARC in neoplastic progression. Semin. Cell Dev. Biol. 21:55–65 [Google Scholar]
  21. Christensen RN, Weinstein M, Tassava RA. 21.  2002. Expression of fibroblast growth factors 4, 8, and 10 in limbs, flanks, and blastemas of Ambystoma. Dev. Dyn. 223:193–203 [Google Scholar]
  22. Clark CJ, Sage EH. 22.  2008. A prototypic matricellular protein in the tumor microenvironment: where there's SPARC, there's fire. J. Cell Biochem. 104:721–32 [Google Scholar]
  23. Claveria C, Giovinazzo G, Sierra R, Torres M. 23.  2013. Myc-driven endogenous cell competition in the early mammalian embryo. Nature 500:39–44 [Google Scholar]
  24. Clevers H. 24.  2006. Wnt/β-catenin signaling in development and disease. Cell 127:469–80 [Google Scholar]
  25. Dalla-Torre CA, Yoshimoto M, Lee CH, Joshua AM, de Toledo SR. 25.  et al. 2006. Effects of THBS3, SPARC and SPP1 expression on biological behavior and survival in patients with osteosarcoma. BMC Cancer 6:237 [Google Scholar]
  26. Davis AC, Wims M, Spotts GD, Hann SR, Bradley A. 26.  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. 7:671–82 [Google Scholar]
  27. De Ferrari GV, Papassotiropoulos A, Biechele T, Wavrant De-Vrieze F, Avila ME. 27.  et al. 2007. Common genetic variation within the low-density lipoprotein receptor-related protein 6 and late-onset Alzheimer's disease. PNAS 104:9434–39 [Google Scholar]
  28. de la Cova C, Abril M, Bellosta P, Gallant P, Johnston LA. 28.  2004. Drosophila myc regulates organ size by inducing cell competition. Cell 117:107–16 [Google Scholar]
  29. Dickins EM, Salinas PC. 29.  2013. Wnts in action: from synapse formation to synaptic maintenance. Front. Cell Neurosci. 7:162 [Google Scholar]
  30. Dong J, Feldmann G, Huang J, Wu S, Zhang N. 30.  et al. 2007. Elucidation of a universal size-control mechanism in Drosophila and mammals. Cell 130:1120–33 [Google Scholar]
  31. Doyle TF, Bellugi U, Korenberg JR, Graham J. 31.  2004. “Everybody in the world is my friend.” Hypersociability in young children with Williams syndrome. Am. J. Med. Genet. A 124A:263–73 [Google Scholar]
  32. Engel FB, Hsieh PC, Lee RT, Keating MT. 32.  2006. FGF1/p38 MAP kinase inhibitor therapy induces cardiomyocyte mitosis, reduces scarring, and rescues function after myocardial infarction. PNAS 103:15546–51 [Google Scholar]
  33. Engel FB, Schebesta M, Duong MT, Lu G, Ren S. 33.  et al. 2005. p38 MAP kinase inhibition enables proliferation of adult mammalian cardiomyocytes. Genes Dev. 19:1175–87 [Google Scholar]
  34. Fenouille N, Robert G, Tichet M, Puissant A, Dufies M. 34.  et al. 2011. The p53/p21Cip1/Waf1 pathway mediates the effects of SPARC on melanoma cell cycle progression. Pigment Cell Melanoma Res. 24:219–32 [Google Scholar]
  35. Froldi F, Ziosi M, Garoia F, Pession A, Grzeschik NA. 35.  et al. 2010. The lethal giant larvae tumour suppressor mutation requires dMyc oncoprotein to promote clonal malignancy. BMC Biol. 8:33 [Google Scholar]
  36. Fukada S, Yamaguchi M, Kokubo H, Ogawa R, Uezumi A. 36.  et al. 2011. Hesr1 and Hesr3 are essential to generate undifferentiated quiescent satellite cells and to maintain satellite cell numbers. Development 138:4609–19 [Google Scholar]
  37. Ghosh S, Roy S, Seguin C, Bryant SV, Gardiner DM. 37.  2008. Analysis of the expression and function of Wnt-5a and Wnt-5b in developing and regenerating axolotl (Ambystoma mexicanum) limbs. Dev. Growth Differ. 50:289–97 [Google Scholar]
  38. Giraldez AJ, Cohen SM. 38.  2003. Wingless and Notch signaling provide cell survival cues and control cell proliferation during wing development. Development 130:6533–43 [Google Scholar]
  39. Goldberg JL, Barres BA. 39.  2000. The relationship between neuronal survival and regeneration. Annu. Rev. Neurosci. 23:579–612 [Google Scholar]
  40. Hackam AS. 40.  2005. The Wnt signaling pathway in retinal degenerations. IUBMB Life 57:381–88 [Google Scholar]
  41. Hamblet NS, Lijam N, Ruiz-Lozano P, Wang J, Yang Y. 41.  et al. 2002. Dishevelled 2 is essential for cardiac outflow tract development, somite segmentation and neural tube closure. Development 129:5827–38 [Google Scholar]
  42. Han M, Yang X, Farrington JE, Muneoka K. 42.  2003. Digit regeneration is regulated by Msx1 and BMP4 in fetal mice. Development 130:5123–32 [Google Scholar]
  43. Han MJ, An JY, Kim WS. 43.  2001. Expression patterns of Fgf-8 during development and limb regeneration of the axolotl. Dev. Dyn. 220:40–48 [Google Scholar]
  44. Hatzistergos KE, Quevedo H, Oskouei BN, Hu Q, Feigenbaum GS. 44.  et al. 2010. Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation. Circ. Res. 107:913–22 [Google Scholar]
  45. Heallen T, Zhang M, Wang J, Bonilla-Claudio M, Klysik E. 45.  et al. 2011. Hippo pathway inhibits Wnt signaling to restrain cardiomyocyte proliferation and heart size. Science 332:458–61 [Google Scholar]
  46. Hogan C, Dupre-Crochet S, Norman M, Kajita M, Zimmermann C. 46.  et al. 2009. Characterization of the interface between normal and transformed epithelial cells. Nat. Cell Biol. 11:460–67 [Google Scholar]
  47. Hurlin PJ. 47.  2013. Control of vertebrate development by MYC. Cold Spring Harb. Perspect. Med. 3:a014332 [Google Scholar]
  48. Ieda M, Fu JD, Delgado-Olguin P, Vedantham V, Hayashi Y. 48.  et al. 2010. Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell 142:375–86 [Google Scholar]
  49. Infante JR, Matsubayashi H, Sato N, Tonascia J, Klein AP. 49.  et al. 2007. Peritumoral fibroblast SPARC expression and patient outcome with resectable pancreatic adenocarcinoma. J. Clin. Oncol. 25:319–25 [Google Scholar]
  50. Janzen V, Forkert R, Fleming HE, Saito Y, Waring MT. 50.  et al. 2006. Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a. Nature 443:421–26 [Google Scholar]
  51. Jiang H, Patel PH, Kohlmaier A, Grenley MO, McEwen DG, Edgar BA. 51.  2009. Cytokine/Jak/Stat signaling mediates regeneration and homeostasis in the Drosophila midgut. Cell 137:1343–55 [Google Scholar]
  52. Johnston LA, Prober DA, Edgar BA, Eisenman RN, Gallant P. 52.  1999. Drosophila myc regulates cellular growth during development. Cell 98:779–90 [Google Scholar]
  53. Joyce JA, Pollard JW. 53.  2009. Microenvironmental regulation of metastasis. Nat. Rev. Cancer 9:239–52 [Google Scholar]
  54. Kahn M. 54.  2014. Can we safely target the WNT pathway?. Nat. Rev. Drug Discov. 13:513–32 [Google Scholar]
  55. Kajita M, Hogan C, Harris AR, Dupre-Crochet S, Itasaki N. 55.  et al. 2010. Interaction with surrounding normal epithelial cells influences signalling pathways and behaviour of Src-transformed cells. J. Cell Sci. 123:171–80 [Google Scholar]
  56. Karpowicz P, Perez J, Perrimon N. 56.  2010. The Hippo tumor suppressor pathway regulates intestinal stem cell regeneration. Development 137:4135–45 [Google Scholar]
  57. Kato Y, Nagashima Y, Baba Y, Kawano T, Furukawa M. 57.  et al. 2005. Expression of SPARC in tongue carcinoma of stage II is associated with poor prognosis: an immunohistochemical study of 86 cases. Int. J. Mol. Med. 16:263–68 [Google Scholar]
  58. Khan P, Linkhart B, Simon HG. 58.  2002. Different regulation of T-box genes Tbx4 and Tbx5 during limb development and limb regeneration. Dev. Biol. 250:383–92 [Google Scholar]
  59. Kikuchi K, Poss KD. 59.  2012. Cardiac regenerative capacity and mechanisms. Annu. Rev. Cell Dev. Biol. 28:719–41 [Google Scholar]
  60. Kokubu C, Heinzmann U, Kokubu T, Sakai N, Kubota T. 60.  et al. 2004. Skeletal defects in ringelschwanz mutant mice reveal that Lrp6 is required for proper somitogenesis and osteogenesis. Development 131:5469–80 [Google Scholar]
  61. Koukourakis MI, Giatromanolaki A, Brekken RA, Sivridis E, Gatter KC. 61.  et al. 2003. Enhanced expression of SPARC/osteonectin in the tumor-associated stroma of non-small cell lung cancer is correlated with markers of hypoxia/acidity and with poor prognosis of patients. Cancer Res. 63:5376–80 [Google Scholar]
  62. Krishnamurthy J, Ramsey MR, Ligon KL, Torrice C, Koh A. 62.  et al. 2006. p16INK4a induces an age-dependent decline in islet regenerative potential. Nature 443:453–57 [Google Scholar]
  63. Laflamme MA, Murry CE. 63.  2011. Heart regeneration. Nature 473:326–35 [Google Scholar]
  64. Lavie CJ, Gersh BJ. 64.  1990. Mechanical and electrical complications of acute myocardial infarction. Mayo Clin. Proc. 65:709–30 [Google Scholar]
  65. Le Grand F, Jones AE, Seale V, Scime A, Rudnicki MA. 65.  2009. Wnt7a activates the planar cell polarity pathway to drive the symmetric expansion of satellite stem cells. Cell Stem Cell 4:535–47 [Google Scholar]
  66. L'Episcopo F, Serapide MF, Tirolo C, Testa N, Caniglia S. 66.  et al. 2011. A Wnt1 regulated Frizzled-1/β-catenin signaling pathway as a candidate regulatory circuit controlling mesencephalic dopaminergic neuron-astrocyte crosstalk: therapeutical relevance for neuron survival and neuroprotection. Mol. Neurodegener. 6:49 [Google Scholar]
  67. Levayer R, Moreno E. 67.  2013. Mechanisms of cell competition: themes and variations. J. Cell Biol. 200:689–98 [Google Scholar]
  68. Li B, Zhong L, Yang X, Andersson T, Huang M, Tang SJ. 68.  2011. WNT5A signaling contributes to Aβ-induced neuroinflammation and neurotoxicity. PLOS ONE 6:e22920 [Google Scholar]
  69. Li W, Baker NE. 69.  2007. Engulfment is required for cell competition. Cell 129:1215–25 [Google Scholar]
  70. Liang JF, Wang HK, Xiao H, Li N, Cheng CX. 70.  et al. 2010. Relationship and prognostic significance of SPARC and VEGF protein expression in colon cancer. J. Exp. Clin. Cancer Res. 29:71 [Google Scholar]
  71. Liang Q, Molkentin JD. 71.  2003. Redefining the roles of p38 and JNK signaling in cardiac hypertrophy: dichotomy between cultured myocytes and animal models. J. Mol. Cell. Cardiol. 35:1385–94 [Google Scholar]
  72. Liebner S, Plate KH. 72.  2010. Differentiation of the brain vasculature: the answer came blowing by the Wnt. J. Angiogenes Res. 2:1 [Google Scholar]
  73. Liu D, Xu H, Shih C, Wan Z, Ma X. 73.  et al. 2015. T-B-cell entanglement and ICOSL-driven feed-forward regulation of germinal centre reaction. Nature 517:214–18 [Google Scholar]
  74. Liu H, Fergusson MM, Castilho RM, Liu J, Cao L. 74.  et al. 2007. Augmented Wnt signaling in a mammalian model of accelerated aging. Science 317:803–6 [Google Scholar]
  75. Maki N, Suetsugu-Maki R, Tarui H, Agata K, Del Rio-Tsonis K, Tsonis PA. 75.  2009. Expression of stem cell pluripotency factors during regeneration in newts. Dev. Dyn. 238:1613–16 [Google Scholar]
  76. Mantoni TS, Schendel RR, Rodel F, Niedobitek G, Al-Assar O. 76.  et al. 2008. Stromal SPARC expression and patient survival after chemoradiation for non-resectable pancreatic adenocarcinoma. Cancer Biol. Ther. 7:1806–15 [Google Scholar]
  77. Massi D, Franchi A, Borgognoni L, Reali UM, Santucci M. 77.  1999. Osteonectin expression correlates with clinical outcome in thin cutaneous malignant melanomas. Hum. Pathol. 30:339–44 [Google Scholar]
  78. Menendez J, Perez-Garijo A, Calleja M, Morata G. 78.  2010. A tumor-suppressing mechanism in Drosophila involving cell competition and the Hippo pathway. PNAS 107:14651–56 [Google Scholar]
  79. Merino MM, Rhiner C, Lopez-Gay JM, Buechel D, Hauert B, Moreno E. 79.  2015. Elimination of unfit cells maintains tissue health and prolongs lifespan. Cell 160:461–76 [Google Scholar]
  80. Meyer SN, Amoyel M, Bergantinos C, de la Cova C, Schertel C. 80.  et al. 2014. An ancient defense system eliminates unfit cells from developing tissues during cell competition. Science 346:6214 [Google Scholar]
  81. Milan M. 81.  2002. Survival of the fittest. Cell competition in the Drosophila wing. EMBO Rep. 3:724–25 [Google Scholar]
  82. Mirotsou M, Zhang Z, Deb A, Zhang L, Gnecchi M. 82.  et al. 2007. Secreted frizzled related protein 2 (Sfrp2) is the key Akt-mesenchymal stem cell–released paracrine factor mediating myocardial survival and repair. PNAS 104:1643–48 [Google Scholar]
  83. Mok SC, Chan WY, Wong KK, Muto MG, Berkowitz RS. 83.  1996. SPARC, an extracellular matrix protein with tumor-suppressing activity in human ovarian epithelial cells. Oncogene 12:1895–901 [Google Scholar]
  84. Molofsky AV, Slutsky SG, Joseph NM, He S, Pardal R. 84.  et al. 2006. Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing. Nature 443:448–52 [Google Scholar]
  85. Morata G, Ripoll P. 85.  1975. Minutes: mutants of Drosophila autonomously affecting cell division rate. Dev. Biol. 42:211–21 [Google Scholar]
  86. Moreno E. 86.  2008. Is cell competition relevant to cancer?. Nat. Rev. Cancer 8:141–47 [Google Scholar]
  87. Moreno E, Basler K. 87.  2004. dMyc transforms cells into super-competitors. Cell 117:117–29 [Google Scholar]
  88. Moreno E, Basler K, Morata G. 88.  2002. Cells compete for decapentaplegic survival factor to prevent apoptosis in Drosophila wing development. Nature 416:755–59 [Google Scholar]
  89. Mourikis P, Sambasivan R, Castel D, Rocheteau P, Bizzarro V, Tajbakhsh S. 89.  2012. A critical requirement for notch signaling in maintenance of the quiescent skeletal muscle stem cell state. Stem Cells 30:243–52 [Google Scholar]
  90. Mullen LM, Bryant SV, Torok MA, Blumberg B, Gardiner DM. 90.  1996. Nerve dependency of regeneration: the role of Distal-less and FGF signaling in amphibian limb regeneration. Development 122:3487–97 [Google Scholar]
  91. Neto-Silva RM, de Beco S, Johnston LA. 91.  2010. Evidence for a growth-stabilizing regulatory feedback mechanism between Myc and Yorkie, the Drosophila homolog of Yap. Dev. Cell 19:507–20 [Google Scholar]
  92. Norman M, Wisniewska KA, Lawrenson K, Garcia-Miranda P, Tada M. 92.  et al. 2012. Loss of Scribble causes cell competition in mammalian cells. J. Cell Sci. 125:59–66 [Google Scholar]
  93. Oertel M, Menthena A, Dabeva MD, Shafritz DA. 93.  2006. Cell competition leads to a high level of normal liver reconstitution by transplanted fetal liver stem/progenitor cells. Gastroenterology 130:507–20; quiz 90 [Google Scholar]
  94. Ohlstein B, Spradling A. 94.  2006. The adult Drosophila posterior midgut is maintained by pluripotent stem cells. Nature 439:470–74 [Google Scholar]
  95. Ohlstein B, Spradling A. 95.  2007. Multipotent Drosophila intestinal stem cells specify daughter cell fates by differential notch signaling. Science 315:988–92 [Google Scholar]
  96. Oliver ER, Saunders TL, Tarle SA, Glaser T. 96.  2004. Ribosomal protein L24 defect in belly spot and tail (Bst), a mouse Minute. Development 131:3907–20 [Google Scholar]
  97. Pan D. 97.  2010. The hippo signaling pathway in development and cancer. Dev. Cell 19:491–505 [Google Scholar]
  98. Pastor-Pareja JC, Xu T. 98.  2013. Dissecting social cell biology and tumors using Drosophila genetics. Annu. Rev. Genet. 47:51–74 [Google Scholar]
  99. Penzo-Mendez AI, Stanger BZ. 99.  2014. Cell competition in vertebrate organ size regulation. Wiley Interdiscip. Rev. Dev. Biol. 3:419–27 [Google Scholar]
  100. Petrova E, Lopez-Gay JM, Rhiner C, Moreno E. 100.  2012. Flower-deficient mice have reduced susceptibility to skin papilloma formation. Dis. Models Mech. 5:553–61 [Google Scholar]
  101. Petrova E, Soldini D, Moreno E. 101.  2011. The expression of SPARC in human tumors is consistent with its role during cell competition. Commun. Integr. Biol. 4:171–74 [Google Scholar]
  102. Pinson KI, Brennan J, Monkley S, Avery BJ, Skarnes WC. 102.  2000. An LDL-receptor-related protein mediates Wnt signalling in mice. Nature 407:535–38 [Google Scholar]
  103. Portela M, Casas-Tinto S, Rhiner C, Lopez-Gay JM, Dominguez O. 103.  et al. 2010. Drosophila SPARC is a self-protective signal expressed by loser cells during cell competition. Dev. Cell 19:562–73 [Google Scholar]
  104. Poss KD. 104.  2010. Advances in understanding tissue regenerative capacity and mechanisms in animals. Nat. Rev. Genet. 11:710–22 [Google Scholar]
  105. Potts RA, Dreher B, Bennett MR. 105.  1982. The loss of ganglion cells in the developing retina of the rat. Brain Res. 255:481–86 [Google Scholar]
  106. Prober DA, Edgar BA. 106.  2000. Ras1 promotes cellular growth in the Drosophila wing. Cell 100:435–46 [Google Scholar]
  107. Ramos-Cabrer P, Campos F, Sobrino T, Castillo J. 107.  2011. Targeting the ischemic penumbra. Stroke 42:S7–11 [Google Scholar]
  108. Reginelli AD, Wang YQ, Sassoon D, Muneoka K. 108.  1995. Digit tip regeneration correlates with regions of Msx1 (Hox 7) expression in fetal and newborn mice. Development 121:1065–76 [Google Scholar]
  109. Reimer KA, Jennings RB. 109.  1979. The “wavefront phenomenon” of myocardial ischemic cell death. II. Transmural progression of necrosis within the framework of ischemic bed size (myocardium at risk) and collateral flow. Lab. Investig. 40:633–44 [Google Scholar]
  110. Ren F, Wang B, Yue T, Yun EY, Ip YT, Jiang J. 110.  2010. Hippo signaling regulates Drosophila intestine stem cell proliferation through multiple pathways. PNAS 107:21064–69 [Google Scholar]
  111. Rhiner C, Lopez-Gay JM, Soldini D, Casas-Tinto S, Martin FA. 111.  et al. 2010. Flower forms an extracellular code that reveals the fitness of a cell to its neighbors in Drosophila. Dev. Cell 18:985–98 [Google Scholar]
  112. Rich JN, Hans C, Jones B, Iversen ES, McLendon RE. 112.  et al. 2005. Gene expression profiling and genetic markers in glioblastoma survival. Cancer Res. 65:4051–58 [Google Scholar]
  113. Rumyantsev PP. 113.  1977. Interrelations of the proliferation and differentiation processes during cardiact myogenesis and regeneration. Int. Rev. Cytol. 51:186–273 [Google Scholar]
  114. Sancho M, Di-Gregorio A, George N, Pozzi S, Sanchez JM. 114.  et al. 2013. Competitive interactions eliminate unfit embryonic stem cells at the onset of differentiation. Dev. Cell 26:19–30 [Google Scholar]
  115. Satoh A, Graham GM, Bryant SV, Gardiner DM. 115.  2008. Neurotrophic regulation of epidermal dedifferentiation during wound healing and limb regeneration in the axolotl (Ambystoma mexicanum). Dev. Biol. 319:321–35 [Google Scholar]
  116. Shaw RL, Kohlmaier A, Polesello C, Veelken C, Edgar BA, Tapon N. 116.  2010. The Hippo pathway regulates intestinal stem cell proliferation during Drosophila adult midgut regeneration. Development 137:4147–58 [Google Scholar]
  117. Simpson P. 117.  1979. Parameters of cell competition in the compartments of the wing disc of Drosophila. Dev. Biol. 69:182–93 [Google Scholar]
  118. Simpson P, Morata G. 118.  1981. Differential mitotic rates and patterns of growth in compartments in the Drosophila wing. Dev. Biol. 85:299–308 [Google Scholar]
  119. Staley BK, Irvine KD. 119.  2010. Warts and Yorkie mediate intestinal regeneration by influencing stem cell proliferation. Curr. Biol. 20:1580–87 [Google Scholar]
  120. Staley BK, Irvine KD. 120.  2012. Hippo signaling in Drosophila: recent advances and insights. Dev. Dyn. 241:3–15 [Google Scholar]
  121. Stoick-Cooper CL, Moon RT, Weidinger G. 121.  2007. Advances in signaling in vertebrate regeneration as a prelude to regenerative medicine. Genes Dev. 21:1292–315 [Google Scholar]
  122. Tajbakhsh S, Borello U, Vivarelli E, Kelly R, Papkoff J. 122.  et al. 1998. Differential activation of Myf5 and MyoD by different Wnts in explants of mouse paraxial mesoderm and the later activation of myogenesis in the absence of Myf5. Development 125:4155–62 [Google Scholar]
  123. Takahashi K, Yamanaka S. 123.  2006. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–76 [Google Scholar]
  124. Tamori Y, Bialucha CU, Tian AG, Kajita M, Huang YC. 124.  et al. 2010. Involvement of Lgl and Mahjong/VprBP in cell competition. PLOS Biol. 8:e1000422 [Google Scholar]
  125. Tarlinton D, Good-Jacobson K. 125.  2013. Diversity among memory B cells: origin, consequences, and utility. Science 341:1205–11 [Google Scholar]
  126. Tyler DM, Li W, Zhuo N, Pellock B, Baker NE. 126.  2007. Genes affecting cell competition in Drosophila. Genetics 175:643–57 [Google Scholar]
  127. Victora GD, Nussenzweig MC. 127.  2012. Germinal centers. Annu. Rev. Immunol. 30:429–57 [Google Scholar]
  128. Villa del Campo C, Claveria C, Sierra R, Torres M. 128.  2014. Cell competition promotes phenotypically silent cardiomyocyte replacement in the mammalian heart. Cell Rep. 8:1741–51 [Google Scholar]
  129. Vincent JP, Kolahgar G, Gagliardi M, Piddini E. 129.  2011. Steep differences in wingless signaling trigger Myc-independent competitive cell interactions. Dev. Cell 21:366–74 [Google Scholar]
  130. von Gise A, Lin Z, Schlegelmilch K, Honor LB, Pan GM. 130.  et al. 2012. YAP1, the nuclear target of Hippo signaling, stimulates heart growth through cardiomyocyte proliferation but not hypertrophy. PNAS 109:2394–99 [Google Scholar]
  131. Wang YX, Rudnicki MA. 131.  2012. Satellite cells, the engines of muscle repair. Nat. Rev. Mol. Cell Biol. 13:127–33 [Google Scholar]
  132. Witkiewicz AK, Freydin B, Chervoneva I, Potoczek M, Rizzo W. 132.  et al. 2010. Stromal CD10 and SPARC expression in ductal carcinoma in situ (DCIS) patients predicts disease recurrence. Cancer Biol. Ther. 10:391–96 [Google Scholar]
  133. Xin M, Kim Y, Sutherland LB, Murakami M, Qi X. 133.  et al. 2013. Hippo pathway effector Yap promotes cardiac regeneration. PNAS 110:13839–44 [Google Scholar]
  134. Xin M, Olson EN, Bassel-Duby R. 134.  2013. Mending broken hearts: cardiac development as a basis for adult heart regeneration and repair. Nat. Rev. Mol. Cell Biol. 14:529–41 [Google Scholar]
  135. Yamada T, Ohno S, Kitamura N, Sasabe E, Yamamoto T. 135.  2015. SPARC is associated with carcinogenesis of oral squamous epithelium and consistent with cell competition. Med. Mol. Morphol. 48:129–37 [Google Scholar]
  136. Yamanaka M, Kanda K, Li NC, Fukumori T, Oka N. 136.  et al. 2001. Analysis of the gene expression of SPARC and its prognostic value for bladder cancer. J. Urol. 166:2495–99 [Google Scholar]
  137. Yiu GK, Chan WY, Ng SW, Chan PS, Cheung KK. 137.  et al. 2001. SPARC (secreted protein acidic and rich in cysteine) induces apoptosis in ovarian cancer cells. Am. J. Pathol. 159:609–22 [Google Scholar]
  138. Yu J, Zheng Y, Dong J, Klusza S, Deng WM, Pan D. 138.  2010. Kibra functions as a tumor suppressor protein that regulates Hippo signaling in conjunction with Merlin and Expanded. Dev. Cell 18:288–99 [Google Scholar]
  139. Zhao B, Tumaneng K, Guan KL. 139.  2011. The Hippo pathway in organ size control, tissue regeneration and stem cell self-renewal. Nat. Cell Biol. 13:877–83 [Google Scholar]
  140. Zhao B, Ye X, Yu J, Li L, Li W. 140.  et al. 2008. TEAD mediates YAP-dependent gene induction and growth control. Genes Dev. 22:1962–71 [Google Scholar]
  141. Zhao C, Aviles C, Abel RA, Almli CR, McQuillen P, Pleasure SJ. 141.  2005. Hippocampal and visuospatial learning defects in mice with a deletion of frizzled 9, a gene in the Williams syndrome deletion interval. Development 132:2917–27 [Google Scholar]
  142. Ziosi M, Baena-Lopez LA, Grifoni D, Froldi F, Pession A. 142.  et al. 2010. dMyc functions downstream of Yorkie to promote the supercompetitive behavior of hippo pathway mutant cells. PLOS Genet. 6:e1001140 [Google Scholar]

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error