Abstract
Planarians have a long history of attracting many biologists for the study of regeneration, one of the most intriguing phenomena in postembryonic development. Planarian regeneration absolutely depends on somatic pluripotent stem cells, termed neoblasts, which are distributed throughout the body. Recent progress in applying molecular and genetic approaches, including RNA interference, has provided increasing knowledge about cellular and molecular dynamics in planarian regeneration. Using the freshwater planarian Dugesia japonica as a model, we revealed that interplay between the anterior extracellular signal–regulated kinase (ERK) and posterior ß-catenin signaling pathways can account for the reconstruction of a complete head-to-tail axis via differentiation of neoblasts during regeneration. Notably, our data suggest that these two signals form opposing activity gradients along the anteroposterior axis. Surprisingly, Thomas Hunt Morgan, one of the great early investigators of planarian regeneration, predicted the existence of these two opposing morphogenetic gradients more than a century ago. Thus, our study provides, for the first time, a basic molecular framework for Morgan’s hypothesis in planarian regeneration. Furthermore, our data suggest that the balance between the anterior ERK signaling and posterior ß-catenin signaling varies among planarian species, resulting in drastic differences in the head-regenerative capacity of their tail fragments.
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References
Adell T, Saló E, Boutros M, Bartscherer K (2009) Smed-Evi/Wntless is required for beta-catenin-dependent and -independent processes during planarian regeneration. Development 136:905–910. https://doi.org/10.1242/dev.033761
Adell T, Cebrià F, Saló E (2010) Gradients in planarian regeneration and homeostasis. Cold Spring Harb Perspect Biol 2:a000505. https://doi.org/10.1101/cshperspect.a000505
Agata K, Inoue T (2012) Survey of the differences between regenerative and non-regenerative animals. Dev Growth Differ 54:143–152. https://doi.org/10.1111/j.1440-169X.2011.01323.x
Agata K, Umesono Y (2008) Brain regeneration from pluripotent stem cells in planarian. Philos Trans R Soc Lond Ser B Biol Sci 363:2071–2078. https://doi.org/10.1098/rstb.2008.2260
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 15:433–440. https://doi.org/10.2108/zsj.15.433
Agata K, Tanaka T, Kobayashi C, Kato K, Saitoh Y (2003) Intercalary regeneration in planarians. Dev Dyn 226:308–316. https://doi.org/10.1002/dvdy.10249
Agata K, Saito Y, Nakajima E (2007) Unifying principles of regeneration I: epimorphosis versus morphallaxis. Dev Growth Differ 49:73–78
Almuedo-Castillo M, Sureda-Gómez M, Adell T (2012) Wnt signaling in planarians: new answers to old questions. Int J Dev Biol 56:53–65. https://doi.org/10.1387/ijdb.113451ma
Baguñà J, Saló E, Auladell C (1989) Regeneration and pattern formation in planarians. Evidence that neoblasts are totipotient stem cells and the source of blastema cells. Development 107:77–86
Cebrià F, Kobayashi C, Umesono Y, Nakazawa M, Mineta K, Ikeo K, Gojobori T, Itoh M, Taira M, Sánchez Alvarado A, Agata K (2002a) FGFR-related gene nou-darake restricts brain tissues to the head region of planarians. Nature 419:620–624. https://doi.org/10.1038/nature01042
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 44:135–146. https://doi.org/10.1046/j.1440-169x.2002.00629.x
Eiraku M, Sasai Y (2012) Self-formation of layered neural structures in three-dimensional culture of ES cells. Curr Opin Neurobiol 22:768–777. https://doi.org/10.1016/j.conb.2012.02.005
Evans MJ, Kaufman MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292:154–156. https://doi.org/10.1038/292154a0
Fagotto F (2013) Looking beyond the Wnt pathway for the deep nature of β-catenin. EMBO Rep 14:422–433. https://doi.org/10.1038/embor.2013.45
Gurley KA, Rink JC, Sánchez Alvarado A (2008) ß-catenin defines head versus tail identity during planarian regeneration and homeostasis. Science 319:323–327. https://doi.org/10.1126/science.1150029
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 347:24–39. https://doi.org/10.1016/j.ydbio.2010.08.007
Iglesias M, Gomez-Skarmeta JL, Saló E, Adell T (2008) Silencing of Smed-betacatenin1 generates radial-like hypercephalized planarians. Development 135:1215–1221. https://doi.org/10.1242/dev.020289
Iglesias M, Almuedo-Castillo M, Aboobaker AA, Saló E (2011) Early planarian brain regeneration is independent of blastema polarity mediated by the Wnt/β-catenin pathway. Dev Biol 358:68–78. https://doi.org/10.1016/j.ydbio.2011.07.013
Imajo M, Tsuchiya Y, Nishida E (2006) Regulatory mechanisms and functions of MAP kinase signaling pathways. IUBMB Life 58:312–317. https://doi.org/10.1080/15216540600746393
Inoue T, Kumamoto H, Okamoto K, Umesono Y, Sakai M, Sánchez Alvarado A, Agata K (2004) Morphological and functional recovery of the planarian photosensing system during head regeneration. Zool Sci 21:275–283
Inoue T, Yamashita T, Agata K (2014) Thermosensory signaling by TRPM is processed by brain serotonergic neurons to produce planarian thermotaxis. J Neurosci 34:15701–15714. https://doi.org/10.1523/JNEUROSCI.5379-13.2014
Kobayashi C, Saito Y, Ogawa K, Agata K (2007) Wnt signaling is required for antero-posterior patterning of the planarian brain. Dev Biol 306:714–724. https://doi.org/10.1016/j.ydbio.2007.04.010
Kondoh K, Nishida E (2007) Regulation of MAP kinases by MAP kinase phosphatases. Biochim Biophys Acta 1773:1227–1237
Kunath T, Saba-El-Leil MK, Almousailleakh M, Wray J, Meloche S, Smith A (2007) FGF stimulation of the Erk1/2 signalling cascade triggers transition of pluripotent embryonic stem cells from self-renewal to lineage commitment. Development 134:2895–2902. https://doi.org/10.1242/dev.02880
Lawrence PA (1988) Background to bicoid. Cell 54:1–2
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 500:81–84. https://doi.org/10.1038/nature12414
Martin GR (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci U S A 78:7634–7638
Morgan TH (1904) The control of heteromorphosis in Planaria maculata. Arch Entw Mech Org 17:683–695
Morgan TH (1905) “Polarity” considered as a phenomenon of gradation of materials. J Exp Zool 2:495–506
Newmark PA, Sánchez Alvarado A (2000) Bromodeoxyuridine specifically labels the regenerative stem cells of planarians. Dev Biol 220:142–153
Nishida E, Gotoh Y (1993) The MAP kinase cascade is essential for diverse signal transduction pathways. Trends Biochem Sci 18:128–131
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 67:1059–1078. https://doi.org/10.1002/dneu.20377
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 59:101–106. https://doi.org/10.1016/j.neures.2007.05.014
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 53:184–192. https://doi.org/10.1016/j.neuint.2008.09.006
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 153:1103–1114. https://doi.org/10.1016/j.neuroscience.2008.03.026
Nishimura K, Kitamura Y, Taniguchi T, Agata K (2010) Analysis of motor function modulated by cholinergic neurons in planarian Dugesia japonica. Neuroscience 168:18–30. https://doi.org/10.1016/j.neuroscience.2010.03.038
Nogi T, Watanabe K (2001) Position-specific and non-colinear expression of the planarian posterior (Abdominal-B-like) gene. Dev Growth Differ 43:177–184. https://doi.org/10.1046/j.1440-169X.2001.00564.x
Ogawa K, Kobayashi C, Hayashi T, Orii H, Watanabe K, Agata K (2002) Planarian fibroblast growth factor receptor homologs expressed in stem cells and cephalic ganglions. Dev Growth Differ 44:191–204. https://doi.org/10.1046/j.1440-169X.2002.00634.x
Okamoto K, Takeuchi K, Agata K (2005) Neural projections in planarian brain revealed by fluorescent dye tracing. Zool Sci 22:535–546. https://doi.org/10.2108/zsj.22.535
Orii H, Sakurai T, Watanabe K (2005) Distribution of the stem cells (neoblasts) in the planarian Dugesia japonica. Dev Genes Evol 215:143–157. https://doi.org/10.1007/s00427-004-0460-y
Petersen CP, Reddien PW (2008) Smed-betacatenin-1 is required for anteroposterior blastema polarity in planarian regeneration. Science 319:327–330. https://doi.org/10.1126/science.1149943
Petersen CP, Reddien PW (2009) A wound-induced Wnt expression program controls planarian regeneration polarity. Proc Natl Acad Sci U S A 106:17061–17066. https://doi.org/10.1073/pnas.0906823106
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 310:1327–1330. https://doi.org/10.1126/science.1116110
Rink JC, Gurley KA, Elliott SA, Sánchez Alvarado A (2009) Planarian Hh signaling regulates regeneration polarity and links Hh pathway evolution to cilia. Science 326:1406–1410. https://doi.org/10.1126/science
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. Zool Sci 17:375–381. https://doi.org/10.2108/jsz.17.375
Salvetti A, Rossi L, Deri P, Batistoni R (2000) An MCM2-related gene is expressed in proliferating cells of intact and regenerating planarians. Dev Dyn 218:603–614. https://doi.org/10.1002/1097-0177(2000)9999:9999<::AID-DVDY1016>3.0.CO;2-C
Sánchez Alvarado A, Newmark PA (1999) Double-stranded RNA specifically disrupts gene expression during planarian regeneration. Proc Natl Acad Sci U S A 96:5049–5054. https://doi.org/10.1073/pnas.96.9.5049
Shibata N, Umesono Y, Orii H, Sakurai T, Watanabe K, Agata K (1999) Expression of vasa(vas)-related genes in germline cells and totipotent somatic stem cells of planarians. Dev Biol 206:73–87. https://doi.org/10.1006/dbio.1998.9130
Shibata N, Rouhana L, Agata K (2010) Cellular and molecular dissection of pluripotent adult somatic stem cells in planarians. Dev Growth Differ 52:27–41. https://doi.org/10.1111/j.1440-169X.2009.01155.x
Shibata N, Kashima M, Ishiko T, Nishimura O, Rouhana L, Misaki K, Yonemura S, Saito K, Siomi H, Siomi MC, Agata K (2016) Inheritance of a nuclear PIWI from pluripotent stem cells by somatic descendants ensures differentiation by silencing transposons in planarian. Dev Cell 37:226–237. https://doi.org/10.1016/j.devcel.2016.04.009
Sikes JM, Newmark PA (2013) Restoration of anterior regeneration in a planarian with limited regenerative ability. Nature 500:77–80. https://doi.org/10.1038/nature12403
Stoick-Cooper CL, Moon RT, Weidinger G (2007) Advances in signaling in vertebrate regeneration as a prelude to regenerative medicine. Genes Dev 21:1292–1315. https://doi.org/10.1101/gad.1540507
Stückemann T, Cleland JP, Werner S, Thi-Kim VH, Bayersdorf R, Liu SY, Friedrich B, Jülicher F, Rink JC (2017) Antagonistic self-organizing patterning systems control maintenance and regeneration of the anteroposterior axis in planarians. Dev Cell 40:248–263. https://doi.org/10.1016/j.devcel.2016.12.024
Sureda-Gómez M, Martín-Durán JM, Adell T (2016) Localization of planarian β-CATENIN-1 reveals multiple roles during anterior–posterior regeneration and organogenesis. Development 143:4149–4160. https://doi.org/10.1242/dev.135152
Takano T, Pulvers JN, Inoue T, Tarui H, Sakamoto H, Agata K, Umesono Y (2007) Regeneration-dependent conditional gene knockdown (Readyknock) in planarian: demonstration of requirement for Djsnap-25 expression in the brain for negative phototactic behavior. Dev Growth Differ 49:383–394. https://doi.org/10.1111/j.1440-169X.2007.00936.x
Tasaki J, Shibata N, Nishimura O, Itomi K, Tabata Y, Son F, Suzuki N, Araki R, Abe M, Agata K, Umesono Y (2011a) ERK signaling controls blastema cell differentiation during planarian regeneration. Development 138:2417–2427. https://doi.org/10.1242/dev.060764
Tasaki J, Shibata N, Sakurai T, Agata K, Umesono Y (2011b) Role of c-Jun N-terminal kinase activity in blastema formation during planarian regeneration. Dev Growth Differ 53:389–400. https://doi.org/10.1111/j.1440-169X.2011.01254.x
Tazaki A, Gaudieri S, Ikeo K, Gojobori T, Watanabe K, Agata K (1999) Neural network in planarian revealed by an antibody against planarian synaptotagmin homologue. Biochem Biophys Res Commun 260:426–432
Umesono Y (2014) Determination of stem cell fate in planarian regeneration. In: Kondoh H, Kuroiwa A (eds) New principles in developmental processes. Springer, Heidelberg, pp 71–83
Umesono Y, Agata K (2009) Evolution and regeneration of the planarian central nervous system. Dev Growth Differ 51:185–195. https://doi.org/10.1111/j.1440-169X.2009.01099.x
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 39:723–727. https://doi.org/10.1046/j.1440-169X.1997.t01-5-00008.x
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 209:31–39
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 34:863–869. https://doi.org/10.1111/j.1460-9568.2011.07819.x
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 500:73–76. https://doi.org/10.1038/nature12359
Wagner DE, Wang IE, Reddien PW (2011) Clonogenic neoblasts are pluripotent adult stem cells that underlie planarian regeneration. Science 332:811–816. https://doi.org/10.1126/science.1203983
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 106:22329–22334. https://doi.org/10.1073/pnas.0907464106
Ying QL, Wray J, Nichols J, Batlle-Morera L, Doble B, Woodgett J, Cohen P, Smith A (2008) The ground state of embryonic stem cell self-renewal. Nature 453:519–523. https://doi.org/10.1038/nature06968
Acknowledgements
I thank Dr. Labib Rouhana and Dr. Kazuya Kobayashi for their critical comments and suggestions on the manuscript, and also Dr. Elizabeth Nakajima for her critical reading of the manuscript. This work was supported by a Grant-in-Aid for Scientific Research on Innovative Areas to Y.U. (22124004) and the Naito Foundation.
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Umesono, Y. (2018). Postembryonic Axis Formation in Planarians. In: Kobayashi, K., Kitano, T., Iwao, Y., Kondo, M. (eds) Reproductive and Developmental Strategies. Diversity and Commonality in Animals. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56609-0_33
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