Development Genes and Evolution

, Volume 217, Issue 11–12, pp 733–748 | Cite as

Regenerating the central nervous system: how easy for planarians!

Review

Abstract

The regenerative capabilities of freshwater planarians (Platyhelminthes) are very difficult to match. A fragment as tiny as 1/279th of the planarian body is able to regenerate a whole animal within very few days [Morgan. Arch Entwm 7:364–397 (1898)]. Although the planarian central nervous system (CNS) may appear quite morphologically simple, recent studies have shown it to be more complex at the molecular level, revealing a high degree of molecular compartmentalization in planarian cephalic ganglia. Planarian neural genes include homologues of well-known transcription factors and genes involved in human diseases, neurotransmission, axon guidance, signaling pathways, and RNA metabolism. The availability of hundreds of genes expressed in planarian neurons coupled with the ability to silence them through the use of RNA interference makes it possible to start unraveling the molecular mechanisms underlying CNS regeneration. In this review, I discuss current knowledge on the planarian nervous system and the genes involved in its regeneration, and I discuss some of the important questions that remain to be answered.

Keywords

Planarian Central nervous system Neural genes Regeneration Axon guidance Neurotransmission 

References

  1. Agata K, Watanabe K (1999) Molecular and cellular aspects of planarian regeneration. Semin Cell Dev Biol 10:77–33Google Scholar
  2. 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. Zoolog Sci 15:433–440PubMedGoogle Scholar
  3. Agata K, Tanaka T, Kobayashi C, Kato K, Saitoh Y (2003) Intercalary regeneration in planarians. Dev Dyn 226:308–316PubMedGoogle Scholar
  4. Araújo SJ, Tear G (2003) Axon guidance mechanisms and molecules: lessons from invertebrates. Nat Rev Neurosci 4:10–92Google Scholar
  5. Asada A, Orii H, Watanabe K, Tsubaki M (2005) Planarian peptidylglycine-hydroxylating monooxygenase, a neuropeptide processing enzyme, colocalizes with cytochrome b561 along the central nervous system. FEBS J 272:942–955Google Scholar
  6. Asami M, Nakatsuka T, Hayashi T, Kou K, Kagawa H, Agata K (2002) Cultivation and characterization of planarian neuronal cells isolated by fluorescence activated cell sorting (FACS). Zoolog Sci 19:1257–1265PubMedGoogle Scholar
  7. Baguñà J (1998) Planarians. In: Geraudie J, Ferretti J (eds) Cellular and molecular basis of regeneration: from invertebrates to humans. Wiley, Chichester, pp 135–165Google Scholar
  8. 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 Morph 155:237–252Google Scholar
  9. Baguñà J, Riutort M (2004) The dawn of bilaterian animals: the case of acoelomorph flatworms. Bioessays 26:1046–1057PubMedGoogle Scholar
  10. Baguñà J, Salo E, Romero R (1989) 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
  11. Bautz A, Schilt J (1986) Somatostatin-like peptide and regeneration capacities in planarians. Gen Comp Endocrinol 64:267–272PubMedGoogle Scholar
  12. Bondi C (1959) Osservazioni sui rapporti tra rigenerazione degli occhi e sistema nervoso in Dugesia lugubris. Arch Zool Ital 44:141–150Google Scholar
  13. Brondsted HV (1969) Planarian regeneration. Pergamon, New YorkGoogle Scholar
  14. Bullock TH, Horridge GA (1965) Platyhelminthes. Structure and function in the nervous systems of invertebrates. Freeman, San Francisco, CAGoogle Scholar
  15. Busch SA, Silver J (2007) The role of extracellular matrix in CNS regeneration. Curr Opin Neurobiol 17:120–127PubMedGoogle Scholar
  16. 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
  17. Cebrià F, Newmark PA (2007) Morphogenesis defects are associated with abnormal nervous system regeneration following roboA RNAi in planarians. Development 134:833–837PubMedGoogle Scholar
  18. Cebrià F, Vispo M, Newmark PA, Bueno D, Romero R (1997) Myocyte differentiation and body wall muscle regeneration in the planarian Girardia tigrina. Dev Genes Evol 207:306–316Google Scholar
  19. Cebrià F, Kobayashi C, Umesono Y, Nakazawa M, Mineta K, Ikeo K, Gojobori T, Itoh M, Taira M, Sanchez Alvarado A, Agata K (2002a) FGFR-related gene nou-darake restricts brain tissues to the head region of planarians. Nature 419:620–624PubMedGoogle Scholar
  20. Cebrià F, Kudome T, Nakazawa M, Mineta K, Ikeo K, Gojobori T, Agata K (2002b) The expression of neural-specific genes reveals the structural and molecular complexity of the planarian central nervous system. Mech Dev 116:199–204PubMedGoogle Scholar
  21. Cebrià F, Nakazawa M, Mineta K, Ikeo K, Gojobori T, Agata K (2002c) Dissecting planarian central nervous system regeneration by the expression of neural-specific genes. Dev Growth Differ 44:135–146PubMedGoogle Scholar
  22. Cebrià F, Guo T, Jopek J, Newmark PA (2007) Regeneration and maintenance of the planarian midline is regulated by a slit orthologue. Dev Biol 307:394–406PubMedGoogle Scholar
  23. 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
  24. Child CM (1904b) Studies on regulation. VI. The relation between the central nervous system and regulation in Leptoplana: anterior and lateral regeneration. J Exp Zool 1:513–558Google Scholar
  25. Chilton JK (2006) Molecular mechanisms of axon guidance. Dev Biol 292:13–24PubMedGoogle Scholar
  26. Dalyell JG (1814) Observations on some interesting phenomena in animal physiology, exhibited by several species of planariae. Edinburgh House, London, UKGoogle Scholar
  27. Dickson BJ, Gilestro GF (2006) Regulation of commissural axon pathfinding by slit and its Robo receptors. Annu Rev Cell Dev Biol 22:651–675PubMedGoogle Scholar
  28. Dinsmore CE, Mescher AL (1998) The role of the nervous system in regeneration. In: Ferretti P, Géraudie J (eds) Cellular and molecular basis of regeneration: from invertebrates to humans. Wiley, Chichester, pp 79–108Google Scholar
  29. Eriksson KS, Panula P (1994) Gamma-aminobutyric acid in the nervous system of a planarian. J Comp Neurol 345:528–536PubMedGoogle Scholar
  30. Fernandes MC, Alvares EP, Gama P, Silveira M (2003) Serotonin in the nervous system of the head region of the land planarian Bipalium kewense. Tissue Cell 35:479–486PubMedGoogle Scholar
  31. Franquinet R (1979) The role of serotonin and catecholamines in the regeneration of the Planaria Polycelis tenvis. J Embryol Exp Morphol 51:85–95PubMedGoogle Scholar
  32. Franquinet R, Le Moigne A (1979) Relation entre les variations des taux de sérotonine et d’ AMP cyclique au cors de la régénération d’ une planaire. Biol Cell 34:71–76Google Scholar
  33. 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
  34. Galtrey CM, Fawcett JW (2007) The role of chondroitin sulfate proteoglycans in regeneration and plasticity in the central nervous system. Brain Res Rev 54:1–18PubMedGoogle Scholar
  35. Goldberg JL (2003) How does an axon grow? Genes Dev 17:941–958PubMedGoogle Scholar
  36. Golubev AI (1988) Glia and neuroglia relationships in the central nervous system of the Turbellaria (Electron microscopic data). Fortschr Zool 36:31–37Google Scholar
  37. Guan KL, Rao Y (2003) Signalling mechanisms mediating neuronal responses to guidance cues. Nat Rev Neurosci 4:941–956PubMedGoogle Scholar
  38. Hutson LD, Chien CB (2002) Pathfinding and error correction by retinal axons: the role of astray/robo2. Neuron 33:205–217PubMedGoogle Scholar
  39. Hyman LH (1951) The invertebrates: Platyhelminthes and Rhynchocoela. McGraw-Hill, New YorkGoogle Scholar
  40. Inatani M (2005) Molecular mechanisms of optic axon guidance. Naturwissenschaften 92:549–561PubMedGoogle Scholar
  41. 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. Zoolog Sci 21:275–283PubMedGoogle Scholar
  42. 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
  43. Ishizuka H, Maezawa T, Kawauchi J, Nodono H, Hirao Y, Nishimura O, Nakagawa H, Sekii K, Tasaka K, Tarui H, Agata K, Hoshi M, Kobayashi K, Sakakibara Y, Matsumoto M (2007) The Dugesia ryukyuensis database as a molecular resource for studying switching of the reproductive system. Zoolog Sci 24:31–37PubMedGoogle Scholar
  44. Johnston RN, Shaw C, Halton DW, Verhaert P, Baguñà J (1995) GYIRFamide: a novel FMRFamide-related peptide (FaRP) from the triclad turbellarian, Dugesia tigrina. Biochem Biophys Res Commun 209:689–697PubMedGoogle Scholar
  45. Kishida Y, Kurabuchi S (1978) The role of the nervous system in the planarian regeneration. I. Regeneration of body fragments deprived of ventral nerve cords. Annot Zool Jpn 51:90–99Google Scholar
  46. Kobayashi C, Saito Y, Ogawa K, Agata K (2007) Wnt signaling is required for antero-posterior patterning of the planarian brain. Dev Biol 306:714–724PubMedGoogle Scholar
  47. 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
  48. Koopowitz H, Chien P (1974) Ultrastructure of the nerve plexus in flatworms. I. Peripheral organization. Cell Tissue Res 155:337–351PubMedGoogle Scholar
  49. Koopowitz H, Chien P (1975) Ultrastructure of nerve plexus in flatworms. II. Sites of synaptic interactions. Cell Tissue Res 157:207–216PubMedGoogle Scholar
  50. Lender T (1955) Some properties of the organisine of eye regeneration in the planaria Polycelis nigra. C R Hebd Seances Acad Sci 240:1726–1728PubMedGoogle Scholar
  51. Lender T (1964) Mise en évidence et role de la neurosécrétion chez les planaires d’eau douce (Turbellariés, Triclades). Ann d’Endocrin 25:61–65Google Scholar
  52. Lender T, Gripon P (1962) La régénération des yeux et du cerveaux de Dugesia lugubris en présence de deux troncs nerveaux inégaux. Bull Soc Zool Fr 87:387–395Google Scholar
  53. Lender T, Klein N (1961) Mise en évidence de cellules sécrétices dans le cerveau de la Planaire POlycelis nigra. Variation de leur nombre au cours de la régénération postérieure. CR Acad Sci 253:331–333Google Scholar
  54. Lentz TL (1968) Primitive nervous systems. Yale University Press, New Haven, CTGoogle Scholar
  55. MacRae EK (1967) The fine structure of sensory receptor processes in the auricular epithelium of the planarian Dugesia tigrina. Z Zellforsch 82:479–494PubMedGoogle Scholar
  56. Mannini L, Rossi L, Deri P, Gremigni V, Salvetti A, Saló 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
  57. Marsal M, Pineda D, Salo 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
  58. Maule AG, Halton DW, Johnston CF, Shaw C, Fairweather I (1990) The serotoninergic, cholinergic and peptidergic components of the nervous system in the monogenean parasite, Diclidophora merlangi: a cytochemical study. Parasitology 100:255–273PubMedGoogle Scholar
  59. 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
  60. McVeigh P, Kimber MJ, Novozhilova E, Day TA (2005) Neuropeptide signalling systems in flatworms. Parasitology 131:S41–S55PubMedGoogle Scholar
  61. 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 ESTs. Proc Natl Acad Sci U S A 100:7666–7671PubMedGoogle Scholar
  62. Morgan TH (1898) Experimental studies of the regeneration of Planaria maculata. Arch Entwicklungsmech Org 7:364–397Google Scholar
  63. Morgan TH (1900) Regeneration in planarians. Arch Entwicklungsmech Org 10:58–119Google Scholar
  64. Morgan TH (1905) “Polarity” considered as a phenomenon of gradation of materials. J Exp Zool 2:495–506Google Scholar
  65. Morita M, Best JB (1965) Electron microscopic studies on Planaria. II. Fine structure of the neurosecretory system in the planarian Dugesia dorotocephala. J Ultrastruct Res 13:396–408PubMedGoogle Scholar
  66. Morita M, Best JB (1966) Electron microscopic studies of Planaria. 3. Some observations on the fine structure of planarian nervous tissue. J Exp Zool 161:391–411PubMedGoogle Scholar
  67. Morita M, Hall F, Best JB, Gern W (1987) Photoperiodic modulation of cephalic melatonin in planarians. J Exp Zool 241:383–388PubMedGoogle Scholar
  68. Morita M, Hall FL, Best JB (1988) An optic neurosecretory cell in the planarian. Fortschr Zool 36:207–210Google Scholar
  69. Nakazawa M, Cebrià 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
  70. Newmark PA, Sánchez Alvarado A (2000) Bromodeoxyuridine specifically labels the regenerative stem cells of planarians. Dev Biol 220:142–153PubMedGoogle Scholar
  71. 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
  72. Newmark PA, Reddien PW, Cebrià F, Sánchez Alvarado A (2003) Ingestion of bacterially expressed double-stranded RNA inhibits gene expression in planarians. Proc Natl Acad Sci U S A 100(Suppl 1):11861–11865PubMedGoogle Scholar
  73. Niclou SP, Ehlert EM, Verhaagen J (2006) Chemorepellent axon guidance molecules in spinal cord injury. J Neurotrauma 23:409–421PubMedGoogle Scholar
  74. Nishimura K, Kitamura Y, Inoue T, Umesono Y, Sano S, Yoshimoto K, Inden M, Takata K, Taniguchi T, Shimohama S, Agata K (2007a) Reconstruction of dopaminergic neural network and locomotion function in planarian regenerates. Dev Neurobiol 67:1059–1078PubMedGoogle Scholar
  75. Nishimura K, Kitamura Y, Inoue T, Umesono Y, Yoshimoto K, Takeuchi K, Taniguchi T, Agata K (2007b) Identification and distribution of tryptophan hydroxylase (TPH)-positive neurons in the planarian Dugesia japonica. Neurosci Res 59:101–106PubMedGoogle Scholar
  76. 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
  77. Ogawa K, Ishihara S, Saito Y, Mineta K, Nakazawa M, Ikeo K, Gojobori T, Watanabe K, Agata K (2002a) Induction of a noggin-like gene by ectopic DV interaction during planarian regeneration. Dev Biol 250:59–70PubMedGoogle Scholar
  78. Ogawa K, Kobayashi C, Hayashi T, Orii H, Watanabe K, Agata K (2002b) Planarian fibroblast growth factor receptor homologs expressed in stem cells and cephalic ganglions. Develop Growth Differ 44:191–204Google Scholar
  79. Okamoto K, Takeuchi K, Agata K (2005) Neural projections in planarian brain revealed by fluorescent dye tracing. Zoolog Sci 22:535–546PubMedGoogle Scholar
  80. Omar HH, Humphries JE, Larsen MJ, Kubiak TM, Geary TG, Maule AG, Kimber MJ, Day TA (2007) Identification of a platyhelminth neuropeptide receptor. Int J Parasitol 37:725–733PubMedGoogle Scholar
  81. Oosaki T, Ishii S (1965) Observations on the ultrastructure of nerve cells in the brain of the planarian, Dugesia gonocephala. Z Zellforsch 66:782–793PubMedGoogle Scholar
  82. Pallas PS (1766) Miscellanea zoologica, quibus novae imprimis atque obscurae animalium species Hagae Comitum, apud Pterum van Cleef, HollandGoogle Scholar
  83. Philippe H, Lartillot N, Brinkmann H (2005) Multigene analyses of bilaterian animals corroborate the monophyly of Ecdysozoa, Lophotrochozoa, and Protostomia. Mol Biol Evol 22:1246–1253PubMedGoogle Scholar
  84. Pineda D, Salo E (2002) Planarian Gtsix3, a member of the Six/so gene family, is expressed in brain branches but not in eye cells. Gene Expr Patterns 2:169–173PubMedGoogle Scholar
  85. 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
  86. Ramón y Cajal S (1928) Degeneration and regeneration of the nervous system. Oxford University Press, LondonGoogle Scholar
  87. Randolph H (1897) Observations and experiments on regeneration in planarians. Arch Entwicklungsmech Org 5:352–372Google Scholar
  88. Reddien PW, Sanchez Alvarado A (2004) Fundamentals of planarian regeneration. Annu Rev Cell Dev Biol 20:725–757PubMedGoogle Scholar
  89. Reddien PW, Bermange AL, Murfitt KJ, Jennings JR, Sanchez Alvarado A (2005) Identification of genes needed for regeneration, stem cell function, and tissue homeostasis by systematic gene perturbation in planaria. Dev Cell 8:635–649PubMedGoogle Scholar
  90. Reisinger E (1972) Die Evolution des Orthogons der Spiralier und daB Archicoelomatenproblem. Z Zool Syst Evolutionforsch 10:1–43CrossRefGoogle Scholar
  91. Reuter M, Gustafsson M (1989) “Neuroendocrine cells” in flatworms—progenitors to metazoan neurons? Arch Histol Cytol 52(Suppl):253–263PubMedGoogle Scholar
  92. Reuter M, Gustafsson MK (1995) The flatworm nervous system: pattern and phylogeny. Exs 72:25–59PubMedGoogle Scholar
  93. Reuter M, Gustafsson M (1996) Neuronal signal substances in asexual multiplication and development in flatworms. Cell Mol Neurobiol 16:591–616PubMedGoogle Scholar
  94. Reuter M, Palmberg I (1989) Development and differentiation of neuronal subsets in asexually reproducing Microstomum lineare. Immunocytochemistry of 5-HT, RF-amide and SCPB. Histochemistry 91:123–131PubMedGoogle Scholar
  95. Reuter M, Gustafsson MK, Sahlgren C, Halton DW, Maule AG, Shaw C (1995a) The nervous system of Tricladida. I. Neuroanatomy of Procerodes littoralis (Maricola, Procerodidae): an immunocytochemical study. Invert Neurosci 1:113–122PubMedGoogle Scholar
  96. Reuter M, Gustafsson MK, Sheiman IM, Terenina N, Halton DW, Maule AG, Shaw C (1995b) The nervous system of Tricladida. II. Neuroanatomy of Dugesia tigrina (Paludicola, Dugesiidae): an immunocytochemical study. Invert Neurosci 1:133–143PubMedGoogle Scholar
  97. 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
  98. 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
  99. Ribeiro P, El-Shehabi F, Patocka N (2005) Classical transmitters and their receptors in flatworms. Parasitology 131:S19–S40PubMedGoogle Scholar
  100. Rieger RM, Tyler S, Smith JPS III, Rieger GE (1991) Platyhelminthes: turbellaria. In: Harrison FW, Bogitsh BJ (eds) Microscopic anatomy of invertebrates, vol. 3. Wiley–Liss, New York, pp 7–140Google Scholar
  101. 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
  102. Ruiz-Trillo I, Paps J, Loukota M, Ribera C, Jondelius U, Baguna J, Riutort M (2002) A phylogenetic analysis of myosin heavy chain type II sequences corroborates that Acoela and Nemertodermatida are basal bilaterians. Proc Natl Acad Sci U S A 99:11246–11251PubMedGoogle Scholar
  103. Sakai F, Agata K, Orii H, Watanabe K (2000) Organization and regeneration ability of spontaneous supernumerary eyes in planarians—eye regeneration field and pathway selection by optic nerves. Zoolog Sci 17:375–381PubMedGoogle Scholar
  104. Saló E (2006) The power of regeneration and the stem-cell kingdom: freshwater planarians (Platyhelminthes). Bioessays 28:546–559PubMedGoogle Scholar
  105. Sánchez Alvarado A (2000) Regeneration in the metazoans: why does it happen? BioEssays 22:578–590PubMedGoogle Scholar
  106. Sánchez Alvarado A, Kang H (2005) Multicellularity, stem cells, and the neoblasts of the planarian Schmidtea mediterranea. Exp Cell Res 306:299–308PubMedGoogle Scholar
  107. Sánchez Alvarado A, Newmark PA (1999) Double-stranded RNA specifically disrupts gene expression during planarian regeneration. Proc Natl Acad Sci U S A 96:5049–5054PubMedGoogle Scholar
  108. Sánchez Alvarado A, Newmark PA, Robb SM, Juste R (2002) The Schmidtea mediterranea database as a molecular resource for studying Platyhelminthes, stem cells and regeneration. Development 129:5659–5665PubMedGoogle Scholar
  109. Sauzin-Monnot MJ (1972) Étude ultrastructurale du tissue nerveux et des produits de secretion nerveuse, au cours des premières heures de regeneration de la planaire Polycelis nigra (Turbellarié-Triclade) au niveau de la blessure. Ann Embryol Morphogen 5:257–265Google Scholar
  110. Selzer ME (2003) Promotion of axonal regeneration in the injured CNS. Lancet Neurol 2:157–166PubMedGoogle Scholar
  111. Sheiman IM, Kreshchenko ND, Sedel, nikov ZV, Groznyi AV (2004) Morphogenesis in planarians Dugesia tigrina. Ontogenez 35:285–290PubMedGoogle Scholar
  112. Singer M (1952) The influence of the nerve in regeneration of the amphibian extremity. Q Rev Biol 27:169–200PubMedGoogle Scholar
  113. 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
  114. Stéphan-Dubois F, Lender Th (1956) Corrélation humorales dans le régénération des planaires paludicoles. Ann Sci Nat Zool 11. serGoogle Scholar
  115. Trawicki W, Czubaj A, Moraczewski J (1988) The brain ultrastructure of Dendrocoelum lacteum (O.F. Muller). Fortschr Zool 36:195–200Google Scholar
  116. Umesono Y, Watanabe K, Agata K (1997) A planarian orthopedia homolog is specifically expressed in the branch region of both the mature and regenerating brain. Dev Growth Differ 39:723–727PubMedGoogle Scholar
  117. 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
  118. Venturini G, Carolei A, Palladini G, Margotta V, Lauro MG (1983) Radioimmunological and immunocytochemical demonstration of Met-enkephalin in planaria. Comp Biochem Physiol C 74:23–25PubMedGoogle Scholar
  119. Wikgren MC, Reuter M (1985) Neuropeptides in a microturbellarian whole-mount immunocytochemistry. Peptides 6(Suppl 3):471–475PubMedGoogle Scholar
  120. Wolff E, Lender T (1950a) Sur le déterminisme de la régénération des yeux chez une planaire d’eau douce Polycelis nigra. CR Séance Soc Biol 144:1213Google Scholar
  121. Wolff E, Lender T (1950b) Sur le role organisateur du cerveau dans la régénération des yeux chez une planaire d’eau douce. CR Acad Sci 230:2238–2239Google Scholar
  122. Zayas RM, Hernandez A, Habermann B, Wang Y, Stary JM, Newmark PA (2005) The planarian Schmidtea mediterranea as a model for epigenetic germ cell specification: analysis of ESTs from the hermaphroditic strain. Proc Natl Acad Sci U S A 102:18491–18496PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  1. 1.Departament de Genètica, Facultat de Biologia and Institut de Biomedicina de la Universitat de Barcelona (IBUB)BarcelonaSpain

Personalised recommendations