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Regeneration and Growth as Modes of Adult Development: The Platyhelminthes as a Case Study

  • Francesc Cebrià
  • Emili Saló
  • Teresa Adell

Abstract

Some species of Platyhelminthes have become model systems in which to study whole-body regeneration in adults. Before describing how this capacity is distributed and varies within the phylum, however, it is important to introduce the adult pluripotent stem cells that confer this remarkable ability in flatworms, the so-called neoblasts.

Keywords

Ventral Nerve Cord Hippo Pathway Hippo Signalling Ventral Cord Blastema Formation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

We thank Bernhard Egger and Jim Collins and Phil Newmark for providing the images of Macrostomum lignano and Schistosoma mansoni, respectively, used in Fig. 4.4. We thank Miquel Vila-Farré for providing the specimens of Phagocata ullala and Camerata robusta used for the immunostainings shown in Fig. 4.4. We thank Maria Almuedo-Castillo for providing planarian images in Fig. 4.3. We thank Iain Patten for advice on the English. This work was supported by grant BFU2012-31701 (Ministerio de Economía y Competitividad, Spain) to F.C, grant BFU2008-01544 (Ministerio de Economía y Competitividad, Spain) to ES, grant 2009SGR1018 (Agència de Gestió d’Ajuts Universitaris i de Recerca) to ES and FC, and grant AIB2010DE-00402 (Ministerio de Economia y Competitividad Accion Integrada) to ES.

References

  1. Adell T, Marsal M, Saló E (2008) Planarian GSK3s are involved in neural regeneration. Dev Genes Evol 218:105–106Google Scholar
  2. Adell T, Saló E, Boutros M, Bartscherer K (2009) Smed-Evi/Wntless is required for b-catenin-dependent and -independent processes during planarian regeneration. Development 136:905–910PubMedGoogle Scholar
  3. Adell T, Cebrià F, Saló E (2010) Gradients in planarian regeneration and homeostasis. Cold Spring Harb Perspect Biol 2(1):a000505PubMedCentralPubMedGoogle Scholar
  4. Adell T, Cebrià F, Saló F (2014) Planarian totipotent stem cells. In: Calegari F, Waskow C (eds) Stem cells from basic research to therapy, vol 1, Basic stem cell biology, tissue formation during development, and model organisms. CRC Press, Boca Raton, pp 433–472Google Scholar
  5. Agata K (2003) Regeneration and gene regulation in planarians. Curr Opin Genet Dev 13:492–496PubMedGoogle Scholar
  6. Agata K, Umesono Y (2008) Brain regeneration from pluripotent stem cells in planarian. Philos Trans R Soc Lond B Biol Sci 363:2071–2078PubMedCentralPubMedGoogle Scholar
  7. Agata K, Soejima Y, Kato K, Kobayashi C, Umesono Y, Watanabe K (1998) Structure of the planarian central nervous system (CNS) revealed by neuronal cell markers. Zool Sci 15:433–440PubMedGoogle Scholar
  8. Almuedo-Castillo M, Saló E, Adell T (2011) Dishevelled is essential for neural connectivity and planar cell polarity in planarians. Proc Natl Acad Sci U S A 108:2813–2818PubMedCentralPubMedGoogle Scholar
  9. Almuedo-Castillo M, Sureda-Gómez M, Adell T (2012) Wnt signaling in planarians: new answers to old questions. Int J Dev Biol 56:53–65PubMedGoogle Scholar
  10. Artemenko Y, Devreotes PN (2013) Hippo on the move: tumor suppressor regulates adhesion and migration. Cell Cycle 12:535–536PubMedCentralPubMedGoogle Scholar
  11. Ashe HL, Briscoe J (2006) The interpretation of morphogen gradients. Development 133:385–394PubMedGoogle Scholar
  12. Auladell C, García-Valero J, Baguñà J (1993) Ultrastructural localization of RNA in the chromatoid bodies of undifferentiated cells (neoblasts) in planarians by RNase gold complex technique. J Morphol 216:319–326Google Scholar
  13. Baguñà J (1974) A demonstration of a peripheral and a gastrodermal nervous plexus in planarians. Zool Anz 193:240–244Google Scholar
  14. Baguñà J (1976) Mitosis in the intact and regenerating planarian Dugesia mediterranea n. sp. I. Mitotic studies during growth, feeding and starvation. J Exp Zool 195:65–80Google Scholar
  15. Baguñà J (2012) The planarian neoblast: the rambling history of its origin and some current black boxes. Int J Dev Biol 56:19–37PubMedGoogle Scholar
  16. Baguñà J, Ballester R (1978) The nervous system in planarians: peripheral and gastrodermal plexuses, pharynx innervation, and the relationship between central nervous system structure and the acoelomate organization. J Morphol 155:237–252Google Scholar
  17. Baguñà J, Saló E, Auladell C (1989a) Regeneration and pattern formation in planarians. III. Evidence that neoblasts are totipotent stem-cells and the source of blastema cells. Development 107:77–86Google Scholar
  18. Baguñà J, Saló E, Romero R (1989b) Effects of activators and antagonists of the neuropeptides substance P and substance K on cell proliferation in planarians. Int J Dev Biol 33:261–266PubMedGoogle Scholar
  19. Bailly X, Reichert H, Hartenstein V (2013) The urbilaterian brain revisited: novel insights into old questions from new flatworm clades. Dev Genes Evol 223:149–157PubMedGoogle Scholar
  20. Bautz A, Schilt J (1986) Somatostatin-like peptide and regeneration capacities in planarians. Gen Comp Endocrinol 64:267–272PubMedGoogle Scholar
  21. Bely AE (2010) Evolutionary loss of animal regeneration: pattern and process. Integr Comp Biol 50:515–527PubMedGoogle Scholar
  22. Bely AE, Nyberg KG (2010) Evolution of animal regeneration: re-emergence of a field. Trends Ecol Evol 25:161–170PubMedGoogle Scholar
  23. Birnbaum KD, Sánchez-Alvarado A (2008) Slicing across kingdoms: regeneration in plants and animals. Cell 132:697–710PubMedCentralPubMedGoogle Scholar
  24. Brehm K (2010) Echinococcus multilocularis as an experimental model in stem cell research and molecular host-parasite interaction. Parasitology 137:537–555PubMedGoogle Scholar
  25. Brϕndsted HV (1969) Planarian regeneration. Pergamon Press, OxfordGoogle Scholar
  26. Bueno D, Fernàndez-Rodríguez J, Cardona A, Hernàndez-Hernàndez V, Romero R (2002) A novel invertebrate trophic factor related to invertebrate neurotrophins is involved in planarian body regional survival and asexual reproduction. Dev Biol 252:188–201PubMedGoogle Scholar
  27. Bullock TH, Horridge GA (1965) Structure and function in the nervous systems of invertebrates. Freeman, San FranciscoGoogle Scholar
  28. Callaerts P, Muñoz-Mármol AM, Glardon S, Castillo E, Sun H, Li WH, Gehring WJ, Saló E (1999) Isolation and expression of a Pax-6 gene in the regenerating and intact planarian Dugesia(G) tigrina. Proc Natl Acad Sci U S A 96:558–563PubMedCentralPubMedGoogle Scholar
  29. Cardona A, Hartenstein V, Romero R (2005) The embryonic development of the triclad Schmidtea polychroa. Dev Genes Evol 215:109–131PubMedGoogle Scholar
  30. Carpenter KS, Morita M, Best JB (1974) Ultrastructure of the photoreceptor of the planarian Dugesia dorotocephala. I. Normal eye. Cell Tissue Res 148:143–158PubMedGoogle Scholar
  31. Cebrià F (2007) Regenerating the central nervous system: how easy for planarians! Dev Genes Evol 217:733–748PubMedGoogle Scholar
  32. Cebrià F (2008) Organization of the nervous system in the model planarian Schmidtea mediterranea: an immunocytochemical study. Neurosci Res 61:375–384PubMedGoogle Scholar
  33. Cebrià F, Newmark PA (2005) Planarian homologs of netrin and netrin receptor are required for proper regeneration of the central nervous system and the maintenance of nervous system architecture. Development 132:3691–3703PubMedGoogle Scholar
  34. Cebrià F, Newmark PA (2007) Morphogenesis defects are associated with abnormal nervous system regeneration after roboA RNAi in planarians. Development 134:833–837PubMedGoogle Scholar
  35. Cebrià F, Kudome T, Nakazawa M, Mineta K, Ikeo K, Gojobori T, Agata K (2002a) The expression of neural-specific genes reveals the structural and molecular complexity of the planarian central nervous system. Mech Dev 116:199–204PubMedGoogle Scholar
  36. Cebrià F, Nakazawa M, Mineta K, Ikeo K, Gojobori T, Agata K (2002b) Dissecting planarian central nervous system regeneration by the expression of neural-specific genes. Dev Growth Differ 44:135–146PubMedGoogle Scholar
  37. Cebrià F, Kobayashi C, Umesono Y, Nakazawa M, Mineta K, Ikeo K, Gojobori T, Itoh M, Taira M, Sánchez-Alvarado A, Agata K (2002c) FGFR-related gene nou-darake restricts brain tissues to the head region of planarians. Nature 419:620–624PubMedGoogle Scholar
  38. Cebrià F, Guo T, Jopek J, Newmark PA (2007) Regeneration and maintenance of the planarian midline is regulated by a slit ortholog. Dev Biol 307:394–406PubMedCentralPubMedGoogle Scholar
  39. Cebrià F, Adell T, Saló E (2010) Regenerative medicine: lessons from planarians. In: Singh SR (ed) Stem cell, regenerative medicine and cancer. Nova Science Publisher, Hauppauge, NY, pp 29–68Google Scholar
  40. Chai G, Ma C, Bao K, Zheng L, Wang X, Sun Z, Salò E, Adell T, Wu W (2010) Complete functional segregation of planarian beta-catenin-1 and -2 in mediating Wnt signaling and cell adhesion. J Biol Chem 285(31):24120–24130PubMedCentralPubMedGoogle Scholar
  41. Child CM (1904a) Studies on regulation. V. The relation between the central nervous system and regeneration in Leptoplana: posterior regeneration. J Exp Zool 1:463–512Google Scholar
  42. Child CM (1904b) Studies on regulation. VI. The relation between the central nervous system and regeneration in Leptoplana: anterior and lateral regeneration. J Exp Zool 1:513–558Google Scholar
  43. Child CM (1911) Studies on the dynamics of morphogenesis and inheritance in experimental reproduction. I The axial gradient in Planaria dorotocephala as a limiting factor in regulation. J Exp Zool 10:265–320Google Scholar
  44. Ciani L, Salinas PC (2005) WNTs in the vertebrate nervous system: from patterning to neuronal connectivity. Nat Rev Neurosci 6:351–362PubMedGoogle Scholar
  45. Collins JJ 3rd, Hou X, Romanova EV, Lambrus BG, Miller CM, Saberi A, Sweedler JV, Newmark PA (2010) Genome-wide analyses reveal a role for peptide hormones in planarian germline development. PLoS Biol 8:e1000509PubMedCentralPubMedGoogle Scholar
  46. Collins JJ 3rd, King RS, Cogswell A, Williams DL, Newmark PA (2011) An atlas for Schistosoma mansoni organs and life-cycle stages using cell type-specific markers and confocal microscopy. PLoS Negl Trop Dis 5:e1009PubMedCentralPubMedGoogle Scholar
  47. Collins JJ 3rd, Wang B, Lambrus BG, Tharp ME, Iyer H, Nemwark PA (2013) Adult somatic stem cells in the human parasite Schistosoma mansoni. Nature 494:476–479PubMedCentralPubMedGoogle Scholar
  48. Coultas KA, Zhang SM (2012) In vitro cercariae transformation: comparison of mechanical and nonmechanical methods and observation of morphological changes of detached cercariae tails. J Parasitol 98:1257–1261PubMedCentralPubMedGoogle Scholar
  49. Cowles MW, Brown DD, Nisperos SV, Stanley BN, Pearson BJ, Zayas RM (2013) Genome-wide analysis of the bHLH gene family in planarians identifies factors required for adult neurogenesis and neuronal regeneration. Development 140:4691–4702PubMedGoogle Scholar
  50. Croce JC, McClay DR (2006) The canonical Wnt pathway in embryonic axis polarity. Semin Cell Dev Biol 2:168–174Google Scholar
  51. Currie KW, Pearson BJ (2013) Transcription factors lhx1/5-1 and pitx are required for the maintenance and regeneration of serotonergic neurons in planarians. Development 140:3577–3588PubMedGoogle Scholar
  52. Dalyell JG (1814) Observations on some interesting phenomena in animal physiology exhibited by several species of planariae. Archibald Constable & Co, EdinburghGoogle Scholar
  53. De Robertis EM (2009) Spemann’s organizer and the self-regulation of embryonic fields. Mech Dev 126(11–12):925–941PubMedCentralPubMedGoogle Scholar
  54. De Robertis EM, Kuroda H (2004) Dorsal-ventral patterning and neural induction in Xenopus embryos. Annu Rev Cell Dev Biol 20:285–308PubMedCentralPubMedGoogle Scholar
  55. Demircan T, Berezikov E (2013) The Hippo pathway regulates stem cells during homeostasis and regeneration of the flatworm Macrostomum lignano. Stem Cells Dev 22:2174–2185PubMedGoogle Scholar
  56. Dirks U, Gruber-Vodicka HR, Egger B, Ott JA (2012) Proliferation pattern during rostrum regeneration of the symbiotic flatworm Paracatenula galateia: a pulse-chase-pulse analysis. Cell Tissue Res 349:517–525PubMedCentralPubMedGoogle Scholar
  57. Egger B, Ladurner P, Nimeth K, Gschwentner R, Rieger R (2006) The regeneration capacity of the flatworm Macrostomum lignano—on repeated regeneration, rejuvenization, and the minimal size needed for regeneration. Dev Genes Evol 216:565–577PubMedCentralPubMedGoogle Scholar
  58. Egger B, Gschwentner R, Rieger R (2007) Free-living flatworms under the knife: past and present. Dev Genes Evol 217:89–104PubMedCentralPubMedGoogle Scholar
  59. Egger B, Gschwentner R, Hess MW, Nimeth KT, Adamski Z, Willems M, Rieger R, Salvenmoser W (2009) The caudal regeneration blastema is an accumulation of rapidly proliferating stem cells in the flatworm Macrostomum lignano. BMC Dev Biol 9:41PubMedCentralPubMedGoogle Scholar
  60. Eriksson KS, Panula P (1994) Gamma-aminobutyric acid in the nervous system of a planarian. J Comp Neurol 345:528–536PubMedGoogle Scholar
  61. Extravour CG, Akam M (2003) Mechanisms of germ cell specification across the metazoans: epigenesis and preformation. Development 130:5869–5884Google Scholar
  62. Fairweather I, Halton DW (1991) Neuropeptides in platyhelminths. Parasitology 102:S77–S92PubMedGoogle Scholar
  63. Fernández-Taboada E, Moritz S, Zeuschner D, Stehling M, Schöler HR, Saló E, Gentile L (2010) Smed-SmB, a member of the LSm protein superfamily, is essential for chromatoid body organization and planarian stem cell proliferation. Development 137:1055–1065PubMedGoogle Scholar
  64. Fraguas S, Barberán S, Cebrià F (2011) EGFR signalling regulates cell proliferation, differentiation and morphogenesis during planarian regeneration and homeostasis. Dev Biol 56:143–153Google Scholar
  65. Fraguas S, Barberán S, Ibarra B, Stöger L, Cebrià F (2012) Regeneration of neuronal cell types in Schmidtea mediterranea: an immunohistochemical and expression study. Int J Dev Biol 56:143–153PubMedGoogle Scholar
  66. Fraguas S, Barberán S, Iglesias M, Rodríguez-Esteban G, Cebrià F (2014) egr-4, a target of EGFR signalling is required for the formation of the brain primordia and head regeneration in planarians. Development 141:1835–1847PubMedGoogle Scholar
  67. Franquinet R (1979) The role of serotonin and catecholamines in the regeneration of the planaria Polycelis tenuis. J Embryol Exp Morphol 51:85–95PubMedGoogle Scholar
  68. Franquinet R, Le Moigne A, Hanoune J (1978) The adenylate cyclase system of planarian Polycelis tenuis. Activation by serotonin and guanine nucleotides. Biochim Biophys Acta 539:88–97PubMedGoogle Scholar
  69. Fusaoka E, Inoue T, Mineta K, Agata K, Takeuchi K (2006) Structure and function of primitive immunoglobulin superfamily neural cell adhesion molecules: a lesson from studies on planarian. Genes Cells 11:541–555PubMedGoogle Scholar
  70. Garza-Garcia AA, Driscoll PC, Brockes JP (2010) Evidence for the local evolution of mechanisms underlying limb regeneration in salamanders. Integr Comp Biol 50:528–535PubMedGoogle Scholar
  71. Gaviño MA, Reddien P (2011) A Bmp/Admp regulatory circuit controls maintenance and regeneration of dorsal-ventral polarity in planarians. Curr Biol 21:294–299PubMedCentralPubMedGoogle Scholar
  72. Gehring WJ (2002) The genetic control of eye development and its implications for the evolution of the various eye-types. Int J Dev Biol 46:65–73PubMedGoogle Scholar
  73. Gehring WJ, Ikeo K (1999) Pax 6: mastering eye morphogenesis and eye evolution. Trends Genet 15:371–377PubMedGoogle Scholar
  74. Gentile L, Cebrià F, Bartscherer K (2011) The planarian flatworm: an in vivo model for stem cell biology and nervous system regeneration. Dis Model Mech 4:12–19PubMedCentralPubMedGoogle Scholar
  75. González-Sastre A, Molina MD, Saló E (2012) Inhibitory Smads and bone morphogenetic protein (BMP) modulate anterior photoreceptor cell number during planarian eye regeneration. Int J Dev Biol 56:155–163PubMedGoogle Scholar
  76. Gremigni V, Miceli C, Puccinelli I (1980) On the role of germ cells in planarian regeneration. A karyological investigation. J Embryol Exp Morpholog 55:53–63Google Scholar
  77. Guan KL, Rao Y (2003) Signalling mechanisms mediating neuronal responses to guidance cues. Nat Rev Neurosci 4:941–956PubMedGoogle Scholar
  78. Gumbiner BM, Kim NG (2014) The Hippo-YAP signaling pathway and contact inhibition of growth. J Cell Sci 127:709–717PubMedCentralPubMedGoogle Scholar
  79. Guo T, Peters AH, Newmark PA (2006) A Bruno-like gene is required for stem cell maintenance in planarians. Dev Cell 11:159–169PubMedGoogle Scholar
  80. Gurley KA, Rink JC, Sánchez-Alvarado A (2008) b-catenin defines head versus tail identity during planarian regeneration and homeostasis. Science 319:323–327PubMedCentralPubMedGoogle Scholar
  81. Gurley KA, Elliott SA, Simakov O, Schmidt HA, Holstein TW, Sánchez-Alvarado A (2010) Expression of secreted Wnt pathway components reveals unexpected complexity of the planarian amputation response. Dev Biol 347:24–39PubMedCentralPubMedGoogle Scholar
  82. Gustafsson MKS (1987) Immunocytochemical demonstration of neuropeptides and serotonin in the nervous system of adult Schistosoma mansoni. Parasitol Res 74:168–174PubMedGoogle Scholar
  83. Gustafsson MKS, Nässel D, Kuusisto A (1993) Immunocytochemical evidence for the presence of substance P-like peptide in Diphyllobothrium dendriticum. Parasitology 106:83–89PubMedGoogle Scholar
  84. Gustafsson MKS, Terenina NB, Kreshchenko ND, Reuter M, Maule AG, Halton DW (2001) Comparative study of the spatial relationship between nicotinamide adenine dinucleotide phosphate-diaphorase activity, serotonin immunoreactivity, and GYRFamide immunoreactivity and the musculature of the adult liver fluke, Fasciola hepatica (Digenea, Fasciolidae). J Comp Neurol 429:71–79PubMedGoogle Scholar
  85. Gustafsson MKS, Halton DW, Kreshchencko ND, Movsessian SO, Raikova OI, Reuter M, Terenina NB (2002) Neuropeptides in flatworms. Peptides 23:2053–2061PubMedGoogle Scholar
  86. Handberg-Thorsager M, Saló E (2007) The planarian nanos-like gene Smednos is expressed in germline and eye precursor cells during development and regeneration. Dev Genes Evol 217:403–411PubMedGoogle Scholar
  87. Hartenstein V, Jones M (2003) The embryonic development of the bodywall and nervous system of the cestode flatworm Hymenolepis diminuta. Cell Tissue Res 311:427–435PubMedGoogle Scholar
  88. Hayashi S, Tamura K, Yokoyama H (2014) Yap1, transcription regulator in the Hippo signaling pathway, is required for Xenopus limb bud regeneration. Dev Biol 388:57–67PubMedGoogle Scholar
  89. Hesse R (1897) Untersuchungen über die Organe der Lichtempfindung bei niederen Thieren. II. Die Augen der Plathelminthen. Z Wiss Zool 62:527–582Google Scholar
  90. Higuchi S, Hayashi T, Tarui H, Nishimura O, Nishimura K, Shibata N, Sakamoto H, Agata K (2008) Expression and functional analysis of musashi-like genes in planarian CNS regeneration. Mech Dev 125:631–645PubMedGoogle Scholar
  91. Holland LZ (2002) Heads or tails? Amphioxus and the evolution of anterior-posterior patterning in deuterostomes. Dev Biol 24:209–228Google Scholar
  92. Hori I (1989) Observations on planarian epithelization after wounding. J Submicrosc Cytol Pathol 21:307–315PubMedGoogle Scholar
  93. Hubert A, Henderson JM, Ross KG, Cowles MW, Torres J, Zayas RM (2013) Epigenetic regulation of planarian stem cells by the SET1/MLL family of histone methyltransferases. Epigenetics 8:79–91PubMedCentralPubMedGoogle Scholar
  94. Hyman LH (1951) The invertebrates. II. Platyhelminthes and rhynchocoela. The acoelomate bilateria. McGraw-Hill, New YorkGoogle Scholar
  95. Iglesias M, Gomez-Skarmeta JL, Saló E, Adell T (2008) Silencing of Smed-betacatenin1 generates radial-like hypercephalized planarians. Development 135:1215–1221PubMedGoogle Scholar
  96. Iglesias M, Almuedo-Castillo M, Aboobaker AA, Saló E (2011) Early planarian brain regeneration is independent of blastema polarity mediated by the Wnt/b-catenin pathway. Dev Biol 358:68–78PubMedGoogle Scholar
  97. Inoue T, Kumamoto H, Okamoto K, Umesono Y, Sakai M, Sanchez Alvarado A, Agata K (2004) Morphological and functional recovery of the planarian photosensing system during head regeneration. Zool Sci 21:275–283PubMedGoogle Scholar
  98. Inoue T, Hayashi T, Takechi K, Agata K (2007) Clathrin-mediated endocytic signals are required for the regeneration of, as well as homeostasis, in the planarian CNS. Development 134:1679–1689PubMedGoogle Scholar
  99. Joffe BI, Kotikova EA (1991) Distribution of catecholamines in turbellarians (with discussion of neuronal homologies in the Platyhelminthes). Stud Neurosci 13:77–113Google Scholar
  100. Joffe BI, Reuter M (1993) The nervous system of Bothriomolus balticus (Proseriata) – a contribution to the knowledge of the orthogon in the Plathelminthes. Zoomorphology 113:113–127Google Scholar
  101. Johnson R, Halder G (2014) The two faces of Hippo: targeting the Hippo pathway for regenerative medicine and cancer treatment. Nat Rev Drug Discov 13:63–79PubMedCentralPubMedGoogle Scholar
  102. Karling TG (1968) On the genus gnosonesima teisinger (Turbellaria). Sarsia 33:81–108Google Scholar
  103. Knopf F, Hammond C, Chekuru A, Kurth T, Hans S, Weber CW, Mahatma G, Fisher S, Brand M, Schulte-Merker S, Weidinger G (2011) Bone regenerates via dedifferentiation of osteoblasts in the zebrafish fin. Dev Cell 20:713–724PubMedGoogle Scholar
  104. Kobayashi C, Saito Y, Ogawa K, Agata K (2007) Wnt signalling is required for antero-posterior patterning of the planarian brain. Dev Biol 306:714–724PubMedGoogle Scholar
  105. Koinuma S, Umesono Y, Watanabe K, Agata K (2003) The expression of planarian brain factor homologs DjFoxG and DjFoxD. Gene Expr Patterns 3:21–27PubMedGoogle Scholar
  106. Konsavage WM, Yochum GS (2013) Intersection of Hippo/YAP and Wnt/B-catenin signaling pathways. Acta Biochim Biophys Sin (Shanghai) 45:71–79Google Scholar
  107. Korswagen HC, Herman MA, Clevers HC (2000) Distinct beta-catenins mediate adhesion and signalling functions in C. elegans. Nature 406:527–532PubMedGoogle Scholar
  108. Kotikova EA (1986) Comparative characterization of the nervous system of the Turbellaria. Hydrobiologia 132:89–92Google Scholar
  109. Kotikova EA (1991) The orthogon of the plathelminthes and main trends of its evolution. Proc Zool Inst St Petersburg 241:88–111Google Scholar
  110. Kotikova EA, Raikova OI, Reuter M, Gustafsson MKS (2002) The nervous and muscular systems in the free-living flatworm Castrella truncata (Rhabdocoela): an immunocytochemical and phalloidin fluorescence study. Tissue Cell 34:365–374PubMedGoogle Scholar
  111. Koziol U, Krohne G, Brehm K (2013) Anatomy and development of the larval nervous system in Echinococcus multilocularis. Front Zool 10:24PubMedCentralPubMedGoogle Scholar
  112. Koziol U, Rauschendorfer T, Zanon Rodríguez L, Krhone G, Brehm K (2014) The unique stem cell system of the immortal larva of the human parasite Echinococcus multilocularis. Evodevo 5:10PubMedCentralPubMedGoogle Scholar
  113. Kragl M, Knapp D, Nacu E, Khatta S, Maden M, Epperlein HH, Tanaka EM (2009) Cells keep a memory of their tissue origin during axolotl limb regeneration. Nature 460:60–65PubMedGoogle Scholar
  114. Kreshchenko ND, Reuter M, Sheiman IM, Halton DW, Johnston RN, Shaw C, Gustafsson MKS (1999) Relationship between musculature and nervous system in the regenerating pharynx in Girardia tigrina (Plathelminthes). Invertebr Reprod Dev 35:109–125Google Scholar
  115. Kumar A, Brockes JP (2012) Nerve dependence in tissue, organ, and appendage regeneration. Trends Neurosci 35:691–699PubMedGoogle Scholar
  116. Kumar A, Godwin JW, Gates PB, Garza-Garcia AA, Brockes JP (2007) Molecular basis for the nerve dependence of limb regeneration in an adult vertebrate. Science 318:772–777PubMedCentralPubMedGoogle Scholar
  117. Labbé RM, Irimia M, Currie KW, Lin A, Zhu SJ, Brown DD, Ross EJ, Voisin V, Bader GD, Blencowe BJ, Pearson BJ (2012) A comparative transcriptomic analysis reveals conserved features of stem cell pluripotency in planarians and mammals. Stem Cells 30:1734–1745PubMedCentralPubMedGoogle Scholar
  118. Ladurner P, Mair GR, Reiter D, Salvenmoser W, Rieger RM (1997) Serotonergic nervous system of two macrostomid species: recent or ancient divergence? Invert Biol 116:178–191Google Scholar
  119. Ladurner P, Rieger R, Baguñà J (2000) Spatial distribution and differentiation potential of stem cells in hatchlings and adults in the marine platyhelminth Macrostomum sp: a bromodeoxyuridine analysis. Dev Biol 226:231–241PubMedGoogle Scholar
  120. Lapan SW, Reddien PW (2011) dlx and sp6-9 control optic cup regeneration in a prototypic eye. PLoS Genet 7:e1002226PubMedCentralPubMedGoogle Scholar
  121. Lapan SW, Reddien PW (2012) Transcriptome analysis of the planarian eye identifies ovo as a specific regulator of eye regeneration. Cell Rep 2:294–307PubMedCentralPubMedGoogle Scholar
  122. Laumer CE, Giribet G (2014) Inclusive taxon sampling suggest a single, stepwise origin of ectolecithality in Platyhelminthes. Biol J Linn Soc 111:570–588Google Scholar
  123. Leksomboon R, Chaijaroonkhanarak W, Arunyanart C, Umka J, Jones MK, Sripa B (2012) Organization of the nervous system in Opisthorchis viverrini investigated by histochemical and immunohistochemical study. Parasitol Int 61:107–111PubMedGoogle Scholar
  124. Lender T (1955) Some properties of the organisine of eye regeneration in the planaria Polycelis nigra. C R Heabd Seances Acad Sci 240:1726–1728Google Scholar
  125. Lewis J, Slack JM, Wolpert L (1977) Thresholds in development. J Theor Biol 65:579–590PubMedGoogle Scholar
  126. Li VS, Clevers H (2013) Intestinal regeneration: YAP-tumor suppressor and oncoprotein? Curr Biol 23:R110–R112PubMedGoogle Scholar
  127. Lin AY, Pearson BJ (2014) Planarian yorkie/YAP functions to integrate adult stem cell proliferation, organ homeostasis and maintenance of axial patterning. Development 141:1197–1208PubMedGoogle Scholar
  128. Lindholm AM, Reuter M, Gustafsson MKS (1998) The NADPH-diaphorase staining reaction in relation to the aminergic and peptidergic nervous system and the musculature of adult Diphyllobothrium dendriticum. Parasitology 117:283–292PubMedGoogle Scholar
  129. Liu SY, Selck C, Friedrich B, Lutz R, Vila-Farré M, Dahl A, Brandl H, Lakshmanaperumal N, Henry I, Rink JC (2013) Reactivating head regrowth in a regeneration-deficient planarian species. Nature 500:81–84PubMedGoogle Scholar
  130. Logan CY, Miller JR, Ferkowicz MJ, McClay DR (1999) Nuclear beta-catenin is required to specify vegetal cell fates in the sea urchin embryo. Development 126:345–357PubMedGoogle Scholar
  131. Mackay DR, Hu M, Li B et al (2006) The mouse Ovol2 gene is required for cranial neural tube development. Dev Biol 291:38–52PubMedCentralPubMedGoogle Scholar
  132. MacRae EK (1964) Observations on the fine structure of photoreceptor cells in the planarian Dugesia tigrina. J Ultrastruct Res 10:334–349PubMedGoogle Scholar
  133. Mannini L, Rossi L, Deri P, Gremigni V, Salvetti A, Salo E, Batistoni R (2004) Djeyes absent (Djeya) controls prototypic planarian eye regeneration by cooperating with the transcription factor Djsix-1. Dev Biol 269:346–359PubMedGoogle Scholar
  134. Marsal M, Pineda D, Saló E (2003) Gtwnt-5 a member of the wnt family expressed in a subpopulation of the nervous system of the planarian Girardia tigrina. Gene Expr Patterns 3:489–495PubMedGoogle Scholar
  135. Martín-Durán JM, Romero R (2011) Evolutionary implications of morphogenesis and molecular patterning of the blind gut in the planarian Schmidtea polychroa. Dev Biol 352:164–176PubMedGoogle Scholar
  136. Martín-Durán JM, Amaya E, Romero R (2010) Germ layer specification and axial patterning in the embryonic development of the freshwater planarian Schmidtea polychroa. Dev Biol 340:145–158PubMedGoogle Scholar
  137. Martín-Durán JM, Monjo F, Romero R (2012) Morphological and molecular development of the eyes during embryogenesis of the freshwater planarian Schmidtea polychroa. Dev Genes Evol 222:45–54PubMedGoogle Scholar
  138. März M, Seebeck F, Bartscherer K (2013) A Pitx transcription factor controls the establishment and maintenance of the serotonergic lineage in planarians. Development 140:4499–4509PubMedGoogle Scholar
  139. Maule AG, Shaw C, Halton DW, Brennan GP, Johnston CF, Moore S (1992) Neuropeptide F (Moniezia expansa): localization and characterization using specific antisera. Parasitology 105:505–512PubMedGoogle Scholar
  140. McVeigh P, Mair GR, Novozhilova E, Day A, Zamanian M, Marks NJ, KImber MJ, Day TA, Maule AG (2011) Schistosome I/Lamides—a new family of bioactive helminth neuropeptides. Int J Parasitol 41:905–913PubMedCentralPubMedGoogle Scholar
  141. Meinhardt H (1978) Space-dependent cell determination under the control of morphogen gradient. J Theor Biol 74:307–321PubMedGoogle Scholar
  142. Merchant MT, Corella C, Willms K (1997) Autoradiographic analysis of the germinative tissue in evaginated Taenia solium metacestodes. J Parasitol 83:363–367PubMedGoogle Scholar
  143. Miljkovic-Licina M, Chera S, Ghila L, Galliot B (2007) Head regeneration in wild-type hydra requires de novo neurogenesis. Development 134:1191–1201PubMedGoogle Scholar
  144. Mineta K, Nakazawa M, Cebrià F, Ikeo K, Agata K, Gojobori T (2003) Origin and evolutionary process of the CNS elucidated by comparative genomics analysis of planarian ESZTs. Proc Natl Acad Sci U S A 100:7666–7671PubMedCentralPubMedGoogle Scholar
  145. Molina MD, Saló E, Cebrià F (2007) The BMP pathway is essential for re-specification and maintenance of the dorsoventral axis in regenerating and intact planarians. Dev Biol 311:79–94PubMedGoogle Scholar
  146. Molina MD, Saló E, Cebrià F (2009) Expression pattern of the expanded noggin gene family in the planarian Schmidtea mediterranea. Gene Expr Patterns 9:246–253PubMedGoogle Scholar
  147. Molina MD, Saló M, Cebrià F (2011a) Organizing the DV axis during planarian regeneration. Commun Integr Biol 4:498–500PubMedCentralPubMedGoogle Scholar
  148. Molina MD, Neto A, Maeso I, Gómez-Skarmeta JL, Saló E, Cebrià F (2011b) Noggin and noggin-like genes control dorsoventral axis regeneration in planarians. Curr Biol 21:300–305PubMedGoogle Scholar
  149. Moraczewski J (1977) Asexual reproduction and regeneration of Catenula (Turbellaria, Archoophora). Zoomorphology 88:65–80Google Scholar
  150. Morgan TH (1898) Experimental studies of the regeneration of Planaria maculata. Arch Entwickelungsmech Org 7:364–397Google Scholar
  151. Morgan TH (1900) Regeneration in planarians. Arch Entwicklungsmech Org 10:58–119Google Scholar
  152. Morgan TH (1901) Regeneration. Macmillan, New YorkGoogle Scholar
  153. Morgan TH (1904) Polarity and axial heteromorphosis. Am Nat 38:502–505Google Scholar
  154. Morgan TH (1905) “Polarity” considered as a phenomenon of gradation of materials. J Exp Zool 2:495–506Google Scholar
  155. Morris J, Ladurner P, Rieger R, Pfister D, Del Mar De Miguel-Bonet M, Jacobs D, Hartenstein V (2006) The Macrostomum lignano EST database as a molecular resource for studying platyhelminth development and phylogeny. Dev Genes Evol 216:695–707PubMedGoogle Scholar
  156. Nakazawa M, Cebria F, Mineta K, Ikeo K, Agata K, Gojobori T (2003) Search for the evolutionary origin of a brain: planarian brain characterized by microarray. Mol Biol Evol 20:784–791PubMedGoogle Scholar
  157. Newmark PA, Sánchez-Alvarado A (2000) Bromodeoxyuridine specifically labels the regenerative stem cells of planarians. Dev Biol 220:142–153PubMedGoogle Scholar
  158. Newmark PA, Sánchez-Alvarado A (2002) Not your father’s planarian: a classic model enters the era of functional genomics. Nat Rev Genet 3:210–219PubMedGoogle Scholar
  159. Nimeth KT, Egger B, Rieger R, Salvenmoser W, Peter R, Gschwentner R (2007) Regeneration in Macrostomum lignano (Platyhelminthes): cellular dynamics in the neoblast stem cell system. Cell Tissue Res 327:637–646PubMedGoogle Scholar
  160. Nishimura K, Kitamura Y, Inoue T, Umesono Y, Yoshimoto K, Takeuchi K, Taniguchi T, Agata K (2007a) Identification and distribution of tryptophan hydroxylase (TPH)-positive neurons in the planarian Dugesia japonica. Neurosci Res 59:101–106PubMedGoogle Scholar
  161. Nishimura K, Kitamura Y, Inoue T, Umesono Y, Sano S, Yoshimoto K, Inden M, Takata K, Taniguchi T, Shimohama S, Agata K (2007b) Reconstruction of dopaminergic neural network and locomotion function in planarian regenerates. Dev Neurobiol 67:1059–1078PubMedGoogle Scholar
  162. Nishimura K, Kitamura Y, Inoue T, Umesono Y, Yoshimoto K, Taniguchi T, Agata K (2008a) Characterization of tyramine beta-hydroxylase in planarian Dugesia japonica: cloning and expression. Neurochem Int 53:184–192PubMedGoogle Scholar
  163. Nishimura K, Kitamura Y, Umesono Y, Takeuchi K, Takata K, Taniguchi T, Agata K (2008b) Identification of glutamic acid decarboxylase gene and distribution of GABAergic nervous system in the planarian Dugesia japonica. Neuroscience 153:1103–1114PubMedGoogle Scholar
  164. Nogi T, Levin M (2005) Characterization of innexin gene expression and functional roles of gap-junctional communication in planarian regeneration. Dev Biol 287:314–335PubMedGoogle Scholar
  165. O’Donnell M, Chance RK, Bashwa GJ (2009) Axon growth and guidance: receptor regulation and signal transduction. Ann Rev Neurosci 32:383–412PubMedGoogle Scholar
  166. Ogawa K, Ishihara S, Saito Y, Mineta K, Nakazawa M, Ikeo K, Gojobori T, Watanbe K, Agata K (2002a) Induction of a noggin-like gene by ectopic DV interaction during planarian regeneration. Dev Biol 250:59–70PubMedGoogle Scholar
  167. Ogawa K, Kobayashi C, Hayashi T, Orii H, Watanabe K, Agata K (2002b) Planarian fibroblasts growth factor receptor homologs expressed in stem cells and cephalic ganglions. Dev Growth Differ 44:191–204PubMedGoogle Scholar
  168. Onal P, Grün D, Adamidi C, Rybak A, Solana J, Mastrobuoni G, Wang Y, Rahn HP, Chen W, Kempa S, Ziebold U, Rajewsky N (2012) Gene expression of pluripotency determinants is conserved between mammalian and planarian stem cells. EMBO J 31:2755–2769PubMedCentralPubMedGoogle Scholar
  169. Orii H, Watanabe K (2007) Bone morphogenetic protein is required for dorso-ventral patterning in the planarian Dugesia japonica. Dev Growth Differ 49:345–349PubMedGoogle Scholar
  170. Orii H, Katayama T, Sakurai T, Agata K, Watanabe K (1998) Immunohistochemical detection of opsins in turbellarians. Hydrobiologia 383:183–187Google Scholar
  171. Oviedo NJ, Morokuma J, Walentek P, Kema IP, Gu MB, Ahn JM, Hwang JS, Gojobori T, Levin M (2010) Long-range neural and gap junction protein-mediated cues control polarity during planarian regeneration. Dev Biol 339:188–199PubMedCentralPubMedGoogle Scholar
  172. Pallas PS (1774) Spicilegia zoological quibus novae imprimis et obscurae animaliu. Speciosiconibus atque conamentariis illustrator. Fasc. X, BeroliniGoogle Scholar
  173. Palmberg I (1986) Cell migration and differentiation during wound healing and regeneration in Microstomum lineare (Turbellaria). Hydrobiologia 132:181–188Google Scholar
  174. Pan JZ, Halton DW, Shaw C, Maule AG, Johnston CF (1994) Serotonin and neuropeptide immunoreactivities in the intramolluscan stages of three marine trematode parasites. Parasitol Res 80:388–395PubMedGoogle Scholar
  175. Pedersen KJ (1976) Scanning electron microscopical observations on epidermal wound healing in the planarian Dugesia tigrina. Wilhelm Rouxs Arch Dev Biol 179:251–273Google Scholar
  176. Petersen CP, Reddien PW (2008) Smed-bcatenin-1 is required for anteroposterior blastema polarity in planarian regeneration. Science 319:327–330PubMedGoogle Scholar
  177. Petersen CP, Reddien PW (2009) A wound-induced Wnt expression program controls planarian regeneration polarity. Proc Natl Acad Sci U S A 106:17061–17066PubMedCentralPubMedGoogle Scholar
  178. Petersen CP, Reddien PW (2011) Polarized notum activation at wounds inhibits Wnt function to promote planarian head regeneration. Science 332:852–855PubMedCentralPubMedGoogle Scholar
  179. Peterson KJ, Eernisse DJ (2001) Animal phylogeny and the ancestry of bilaterians: inferences from morphology and 18S rDNA gene sequences. Evol Dev 3:170–205PubMedGoogle Scholar
  180. Peterson KJ, Cotton JA, Gehling JG, Pisani D (2008) The Ediacaran emergence of bilaterians: congruence between the genetic and the geological fossil records. Phil Trans Soc B 363:1435–1443Google Scholar
  181. Philippe H, Brinkmann H, Copley RR, Moroz LL, Nakano H, Poustka AJ, Wallberg A, Peterson KJ, Telford MJ (2011) Acoelomorph flatworms are deuterostomes related to Xenoturbella. Nature 470:255–258PubMedCentralPubMedGoogle Scholar
  182. Pichaud F, Treisman J, Desplan C (2001) Reinventing a common strategy for patterning the eye. Cell 105:9–12PubMedGoogle Scholar
  183. Pineda D, Saló E (2002) Planarian Gtsix3, a member of the Six/so gene family, is expressed in brain branches but not in eye cells. Mech Dev 119(suppl1):S161–S171Google Scholar
  184. Pineda D, Gonzalez J, Callaerts P, Ikeo K, Gehring WJ, Saló E (2000) Searching for the prototypic eye genetic network: Sine oculis is essential for eye regeneration in planarians. Proc Natl Acad Sci U S A 97:4525–4529PubMedCentralPubMedGoogle Scholar
  185. Pineda D, Gonzalez J, Marsal M, Saló E (2001) Evolutionary conservation of the initial eye genetic pathway in planarians. Belg J Zool 131:77–82Google Scholar
  186. Pineda D, Rossi L, Batistoni R, Salvetti A, Marsal M, Gremigni V, Falleni A, Gonzalez-Linares J, Deri P, Saló E (2002) The genetic network of prototypic planarian eye regeneration is Pax6 independent. Development 129:1423–1434PubMedGoogle Scholar
  187. Poss KD (2010) Advances in understanding tissue regenerative capacity and mechanisms in animals. Nat Rev Genet 11:710–722PubMedCentralPubMedGoogle Scholar
  188. Randolph H (1892) The regeneration of the tail in Lumbriculus. J Morphol 7:317–344Google Scholar
  189. Randolph H (1897) Observations and experiments on regeneration in planarians. Arch EntwMech Org 5:352–372Google Scholar
  190. Rawlinson KA (2010) Embryonic and post-embryonic development of the polyclad flatworm Maritigrella crozieri; implications for the evolution of spiralian life history traits. Front Zool 7:12PubMedCentralPubMedGoogle Scholar
  191. Reddien PW (2011) Constitutive gene expression and the specification of tissue identity in adult planarian biology. Trends Genet 27:277–285PubMedCentralPubMedGoogle Scholar
  192. Reddien PW (2013) Specialized progenitors and regeneration. Development 140:951–957PubMedCentralPubMedGoogle Scholar
  193. Reddien PW, Oviedo NJ, Jennings JR, Jenkin JC, Sánchez Alvarado A (2005) SMEDWI-2 is a PIWI-like protein that regulates planarian stem cells. Science 310:1327–1330PubMedGoogle Scholar
  194. Reddien PW, Bermange AL, Kicza AM, Sanchez Alvarado A (2007) BMP signaling regulates the dorsal planarian midline and is needed for asymmetric regeneration. Development 134:4043–4051PubMedGoogle Scholar
  195. Reginensi A, Scott RP, Gregorieff A, Bagherie-Lachidan M, Chung C, Lim DS, Pawson T, Wrana J, McNeill H (2013) Yap- and Cdc42-dependent nephrogenesis and morphogenesis during mouse kidney development. PLoS Genet 9:e1003380PubMedCentralPubMedGoogle Scholar
  196. Reisinger E (1972) Die Evolution des Orthogons der Spiralier und das Archicoelomatenproblem. Z Zool Syst Evolutionforsch 10:1–43Google Scholar
  197. Reiter D, Wikgren M (1991) Immunoreactivity to a specific echinoderm neuropeptide in the nervous system of the flatworm Macrostomum hystricinum marinum (Turbellaria, Macrostomida). Hydrobiologia 227:229Google Scholar
  198. Reuter M (1988) Development and organization of nervous system visualized by immunocytochemistry in three flatworm species. Fortschr Zool 36:181–184Google Scholar
  199. Reuter M (1994) Substance P immunoreactivity in sensory structures and the central and pharyngeal nervous system of Stenostomum leucops (Catenulida) and Microstomum lineare (Macrostomida). Cell Tissue Res 276:173–180Google Scholar
  200. Reuter M, Gustafsson MKS (1995) The flatworm nervous system: pattern and phylogeny. In: Breidbach O, Kutsch W (eds) The nervous systems of invertebrates: an evolutionary and comparative approach. Birkhäuser Verlag, Basel, pp 25–59Google Scholar
  201. Reuter M, Gustafsson MKS (1996) Neuronal signal substances in asexual multiplication and development in flatworms. Cell Mol Neurobiol 16:591–616PubMedGoogle Scholar
  202. Reuter M, Halton DW (2001) Comparative neurobiology of Platyhelminthes. In: Littlewood TJ, Bray RA (eds) The interrelationships of Platyhelminthes. Academic, London, pp 239–259Google Scholar
  203. Reuter M, Kreshchenko N (2004) Flatworm asexual multiplication implicates stem cells and regeneration. Can J Zool 82:334–356Google Scholar
  204. Reuter M, Palmberg I (1989) Development and differentiation of neuronal subsets in asexually reproducing Microstomum lineare. Immunocytochemistry of 5-HT, RF-amide and SCPv. Histochemistry 91:123–131PubMedGoogle Scholar
  205. Reuter M, Wikgren M, Lehtonen M (1986) Immunocytochemical demonstration of 5-HT-like and FMRF-amide-like substances in whole mounts of Microstomum lineare (Turbellaria). Cell Tissue Res 246:7–12Google Scholar
  206. Reuter M, Gustafsson MKS, Sheiman IM, Terenina N, Halton DW, Maule AG, Shaw C (1995a) The nervous system of Tricladida. II. Neuroanatomy of Dugesia tigrina (Paludicola, Dugesiidae): an immunocytochemical study. Invertebr Neurosci 1:133–143Google Scholar
  207. Reuter M, Gustafsson MKS, Sahlgren C, Halton DW, Maule AG, Shaw C (1995b) The nervous system of Tricladida. I. Neuroanatomy of Procerodes littoralis (Maricola, Procerodidae): an immunocytochemical study. Invertebr Neurosci 1:113–122Google Scholar
  208. Reuter M, Maule AG, Halton DW, Gustafsson MS, Shaw C (1995c) The organization of the nervous system in Plathelminthes. The neuropeptide F-immunoreactivity pattern in Catenulida, Macrostomida, Proseriata. Zoomorphology 115:83–97Google Scholar
  209. Reuter M, Gustafsson MKS, Mäntylä K, Grimmelikhuijzen CJP (1996a) The nervous system of Tricladida. III. Neuroanatomy of Dendrocoelum lacteum and Polycelis tenuis (Plathelminthes, Paludicola): an immunocytochemical study. Zoomorphology 116:111–122Google Scholar
  210. Reuter M, Sheiman IM, Gustafsson MKS, Halton DW, Maule AG, Shaw C (1996b) Development of the nervous system in Dugesia tigrina during regeneration after fission and decapitation. Invertebr Reprod Dev 29:199–211Google Scholar
  211. Reuter M, Raikova OI, Gustafsson MKS (2001) Patterns in the nervous and muscle systems in lower flatworms. Belg J Zool 131:47–53Google Scholar
  212. Reversade B, De Robertis EM (2005) Regulation of ADMP and BMP2/4/7 at opposite embryonic poles generates a self-regulating morphogenetic field. Cell 123:1147–1160PubMedCentralPubMedGoogle Scholar
  213. Ribeiro P, El-Shehabi F, Patocka N (2005) Classical transmitters and their receptors in flatworms. Parasitology 131:S19–S40PubMedGoogle Scholar
  214. Rieger R, Tyler S, Smith JPS III, Rieger G (1991) Platyhelminthes: Turbellaria. In: Harrison FW, Bogitsh BJ (eds) Microscopic anatomy of invertebrates, vol 3. Wiley-Liss, New York, pp 7–140Google Scholar
  215. Rink J (2013) Stem cell systems and regeneration in planaria. Dev Genes Evol 223:67–84PubMedCentralPubMedGoogle Scholar
  216. Riutort M, Álvarez-Presas M, Lázaro E, Solà E, Paps J (2012) Evolutionary history of the Tricladida and the Platyhelminthes: an up-to-date phylogenetic and systematic account. Int J Dev Biol 56:5–17PubMedGoogle Scholar
  217. Rock JM, Lim D, Stach L, Ogrodowicz RW, Keck JM, Jones MH, Wong CC, Yates JR 3rd, Winey M, Smerdon SJ, Yaffe MB, Amon A (2013) Activation of the yeast Hippo pathway by phosphorylation-dependent assembly of signaling complexes. Science 340:871–875PubMedGoogle Scholar
  218. Rossi L, Batistoni R, Salvetti A, Deri P, Bernini F, Andreoli I, Falleni A, Gremigni V (2001) Molecular aspects of cell proliferation and neurogenesis in planarians. Belg J Zool 131:83–87Google Scholar
  219. Rossi L, Deri P, Andreoli I, Gremigni V, Salvetti A, Batistoni R (2003) Expression of DjXnp, a novel member of the SNF2-like ATP-dependent chromatin remodelling genes, in intact and regenerating planarians. Int J Dev Biol 47:293–298PubMedGoogle Scholar
  220. Rossi L, Salvetti A, Marincola FM, Lena A, Deri P, Mannini L, Batistoni R, Wang E, Gremigni V (2007) Deciphering the molecular machinery of stem cells: a look at the neoblast gene expression profile. Genome Biol 8:R62PubMedCentralPubMedGoogle Scholar
  221. Rouhana L, Shibata N, Nishimura O, Agata K (2010) Different requirements for conserved post-transcriptional regulators in planarian regeneration and stem cell maintenance. Dev Biol 341:429–443PubMedGoogle Scholar
  222. Ruiz-Trillo I, Riutort M, Littlewood DTJ, Herniou EA, Baguñà J (1999) Acoel flatworms: earliest extant bilaterian metazoans, not members of Platyhelminthes. Science 283:1919–1923PubMedGoogle Scholar
  223. Ruppert EE, Schreiner SP (1980) Ultrastructure and potential significance of cerebral light refracting bodies of Stenostomum virginianum (Turbellaria, Catenulida). Zoomorphology 96:21–31Google Scholar
  224. Saló E (2006) The power of regeneration and the stem-cell kingdom: freshwater planarians (Platyhelminthes). Bioessays 28:546–559PubMedGoogle Scholar
  225. Saló E, Baguñà J (1984) Regeneration and pattern formation in planarians. I. The pattern of mitosis in anterior and posterior regeneration in Dugesia (G) tigrina, and a new proposal for blastema formation. J Embryol Exp Morphol 83:63–80PubMedGoogle Scholar
  226. Saló E, Batistoni R (2008) Planarian eye, a simple and plastic system with great regenerative capacity. In: Tsonis PA (ed) Animal models in eye research. Elsevier, AmsterdamGoogle Scholar
  227. Saló E, Pineda D, Marsal M, González J, Gremigni V, Batistoni R (2002) Genetic network of the eye in Platyhelminthes: expression and functional analysis of some players during planarian regeneration. Gene 287:67–74PubMedGoogle Scholar
  228. Salvini-Plawen LV, Mayr E (1977) On the evolution of photoreceptors and eyes. Evol Biol 10:207–263Google Scholar
  229. Sánchez Alvarado A, Newmark PA (1999) Double-stranded RNA specifically disrupts gene expression during planarian regeneration. Proc Natl Acad Sci U S A 96:5049–5054PubMedCentralPubMedGoogle Scholar
  230. Schneider SQ, Finnerty JR, Martindale MQ (2003) Protein evolution: structure-function relationships of the oncogene beta-catenin in the evolution of multicellular animals. J Exp Zool B Mol Dev Evol 295:25–44PubMedGoogle Scholar
  231. Scimone ML, Srivastava M, Bell GW, Reddien PW (2011) A regulatory program for excretory system regeneration in planarians. Development 38:4387–4398Google Scholar
  232. Sebé-Pedrós A, de Mendoza A, Lang BF, Degnan BM, Ruiz-Trillo I (2011) Unexpected repertoire of metazoan transcription factors in the unicellular holozoan Capsaspora owczarzaki. Mol Biol Evol 28:1241–1254PubMedCentralPubMedGoogle Scholar
  233. Semmler H, Chiodin M, Bailly X, Martinez P, Wanninger A (2010) Steps towards a centralized nervous system in basal bilaterians: insights from neurogenesis of the acoel Symsagittifera roscoffensis. Dev Growth Differ 52:701–713PubMedGoogle Scholar
  234. Senft AW, Weller TH (1956) Growth and regeneration of Schistosoma mansoni in vitro. Proc Soc Exp Biol Med 93:16–19PubMedGoogle Scholar
  235. Sheiman IM, Kreshchenko ND, Sedelnikov ZV, Groznyi AV (2004) Morphogenesis in planarians Dugesia tigrina. Ontogenez 35:285–290PubMedGoogle Scholar
  236. Sickes JM, Newmark PA (2013) Restoration of anterior regeneration in a planarian with limited regenerative ability. Nature 500:77–80Google Scholar
  237. Singer M, Craven L (1948) The growth and morphogenesis of the regenerating forelimb of adult Triturus following denervation at various stages of development. J Exp Zool 108:279–308PubMedGoogle Scholar
  238. Sivickis PB (1930) A quantitative study of regeneration along the main axis of the triclad body. Arch Zool Ital 16:430–449Google Scholar
  239. Solana J (2013) Closing the circle of germline and stem cells: the primordial stem cell hypothesis. Evodevo 4:2PubMedCentralPubMedGoogle Scholar
  240. Sopott-Ehlers B (1982) Ultrastruktur potentiell photorezeptorischer Zellen unterschiedlicher Organisation bei einem Proseriat (Platyhelminthes). Zoomorphology 101:165–176Google Scholar
  241. Sopott-Ehlers B, Ehlers U (2003) Eyes covered by mitochondrial lenses in Petaliella spiracauda and Ptychopera purasjokii (Plathelminthes, Rhabdocoela, Trigonostominae). Ultrastructural features and phylogenetic implications. J Submicrosc Cytol Pathol 35:415–421PubMedGoogle Scholar
  242. Sopott-Ehlers B, Kearn GC, Ehlers U (2001) Evidence for the mitochondrial origin of the eye lenses in embryos of Entobdella soleae (Plathelminthes, Monogenea). Parasitol Res 87:421–427PubMedGoogle Scholar
  243. Sperry PJ, Ansevin KD, Tittel FK (1973) The inductive role of the nerve cord in regeneration of isolated postpharyngeal body sections of Dugesia dorotocephala. J Exp Zool 186:159–174PubMedGoogle Scholar
  244. Spiliotis M, Lechner S, Tappe D, Scheller C, Krohne G, Brehm K (2008) Transient transfection of Echinococcus multilocularis primary cells and complete in vitro regeneration of metacestode vesicles. Int J Parasitol 38:1025–1039PubMedGoogle Scholar
  245. Srivastava M, Mazza-Curll KL, van Wolfswinkel JC, Reddien PW (2014) Whole-body acoel regeneration is controlled by Wnt and Bmp-Admp signalling. Curr Biol 24:1107–1113PubMedGoogle Scholar
  246. Stéphan-Dubois F, Lender Th (1956) Corrélation humorales dans le regeneration des planaires paludicoles. Ann Sci Nat Zool 11 serGoogle Scholar
  247. Tamamaki N (1990) Evidence for the phagocytotic removal of photoreceptive membrane by pigment cells in the eye of the planarian, Dugesia japonica. Zool Sci 7:385–393Google Scholar
  248. Tanaka EM, Reddien PW (2011) The cellular basis for animal regeneration. Dev Cell 21:172–185PubMedCentralPubMedGoogle Scholar
  249. Teshirogi W, Ishida S, Yamazaki H (1977) Regenerative capacities of transverse pieces in the two species of freshwater planarian, Dendrocoelopsis lactea and Polycelis sapporo. Sci Rep Hirosaki Univ 24:55–72Google Scholar
  250. Umesono Y, Watanabe K, Agata K (1999) Distinct structural domains in the planarian brain defined by the expression of evolutionarily conserved homeobox genes. Dev Genes Evol 209:31–39PubMedGoogle Scholar
  251. Umesono Y, Tasaki J, Nishimura K, Inoue T, Agata K (2011) Regeneration in an evolutionarily primitive brain—the planarian Dugesia japonica model. Eur J Neurosci 34:863–869PubMedGoogle Scholar
  252. Umesono Y, Tasaki J, Nishimura Y, Hrouda M, Kawaguchi E, Yazawa S, Nishimura O, Hosoda K, Inoue T, Agata K (2013) The molecular logic for planarian regeneration along the anterior-posterior axis. Nature 500:73–76PubMedGoogle Scholar
  253. Verdoodt F, Bert W, Couvreur M, De Mulder K, Willems M (2012) Proliferative response of the stem cell system during regeneration of the rostrum in Macrostomum lignano (Platyhelminthes). Cell Tissue Res 347:397–406PubMedGoogle Scholar
  254. Vorontsova MA, Liosner LD (1960) Asexual propagation and regeneration. Pergamon Press, LondonGoogle Scholar
  255. Wagner DE, Wang IE, Reddien PW (2011) Clonogenic neoblasts are pluripotent adult stem cells that underlie planarian regeneration. Science 332:811–816PubMedCentralPubMedGoogle Scholar
  256. Wagner DE, Ho JJ, Reddien PW (2012) Genetic regulators of a pluripotent adult stem cell system in planarians identified by RNAi and clonal analysis. Cell Stem Cell 10:299–311PubMedCentralPubMedGoogle Scholar
  257. Wang B, Collins JJ 3rd, Newmark PA (2013) Functional characterization of neoblast-like stem cells in larval Schistosoma mansoni. Elife 2:e00768PubMedCentralPubMedGoogle Scholar
  258. Wenemoser D, Reddien PW (2010) Planarian regeneration involves distinct stem cell responses to wounds and tissue absence. Dev Biol 344:979–991PubMedCentralPubMedGoogle Scholar
  259. Wikramanayake AH, Hong M, Lee PN, Pang K, Byrum CA, Bince JM, Xu R, Martindale MQ (2003) An ancient role for nuclear beta-catenin in the evolution of axial polarity and germ layer segregation. Nature 426:446–450PubMedGoogle Scholar
  260. Wolff E, Lender T (1950) Sur le role organisateur du cerveau dans la regeneration des yeux chez une planaire d’eau douce. C R Acad Sci 230:2238–2239Google Scholar
  261. Xin M, Kim Y, Sutherland LB, Murakami M, Qi X, McAnally J, Porrello ER, Mahmoud AI, Tan W, Shelton JM, Richardson JA, Sadek HA, Bassel-Duby R, Olson EN (2013) Hippo pathway effector Yap promotes cardiac regeneration. Proc Natl Acad Sci U S A 110:13839–13844PubMedCentralPubMedGoogle Scholar
  262. Yazawa S, Umesono Y, Hayashi T, Tarui H, Agata K (2009) Planarian Hedgehog/Patched establishes anterior-posterior polarity by regulating Wnt signaling. Proc Natl Acad Sci U S A 106:22329–22334PubMedCentralPubMedGoogle Scholar
  263. Yoshikawa S, McKinnon RD, Kokel M, Thomas JB (2003) Wnt-mediated axon guidance via the Drosophila Derailed receptor. Nature 422:583–588PubMedGoogle Scholar
  264. Younossi-Hartenstein A, Hartenstein V (2000) The embryonic development of the polyclad flatworm Imogine mcgrathi. Dev Genes Evol 210:383–398PubMedGoogle Scholar
  265. Younossi-Hartenstein A, Ehlers U, Hartenstein V (2000) Embryonic development of the nervous system of the rhabdocoel flatworm Mesostoma lingua (Abilgaard 1789). J Comp Neurol 16:461–474Google Scholar
  266. Ypsilanti AR, Zagar Y, Chédotal A (2010) Moving away from the midline: new developments for Slit and Robo. Development 137:1939–1952PubMedGoogle Scholar

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© Springer-Verlag Wien 2015

Authors and Affiliations

  1. 1.Department of Genetics, Faculty of BiologyInstitute of Biomedicine, University of BarcelonaCatalunya, BarcelonaSpain

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