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Regeneration and Development in Animals

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Abstract

Regeneration capabilities are found in most or all animals. Whether regeneration is part of the development of an animal or a distinct phenomenon independent of development is a debatable question. If we consider regeneration as a process belonging to development, similarly to embryogenesis or metamorphosis, the existence of regenerative capabilities in adults can be seen as an argument in favor of the theory that development continues throughout the life of animals. Here I perform a comparative analysis of regeneration versus “classical” developmental processes in animals in order to determine to what extent these processes are inclusive or distinct. I identify the existence of regeneration-specific processes, i.e., processes that occur during the regeneration, but not the initial development, of a given structure. In addition, I find that seemingly similar processes acting during development and regeneration may have differential molecular and cellular bases. I thus conclude that there are significant differences between regeneration processes in adult animals and developmental processes occurring during earlier phases of the life cycle. The existence of regenerative capabilities in adult animals can therefore not be used as an argument in favor of the idea that development spans the whole life.

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References

  • Allan CH, Fleckman P, Fernandes RJ, Hager B, James J, Wisecarver Z, Satterstrom FK, Gutierrez A, Norman A, Pirrone A, Underwood RA, Rubin BP, Zhang M, Ramay HR, Clark JM (2006) Tissue response and Msx1 expression after human fetal digit tip amputation in vitro. Wound Repair Regen 14(4):398–404

    Article  Google Scholar 

  • Bäckhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI (2005) Host-bacterial mutualism in the human intestine. Science 307:1915–1920

    Article  Google Scholar 

  • Beck CW, Izpisúa Belmonte JC, Christen B (2009) Beyond early development: Xenopus as an emerging model for the study of regenerative mechanisms. Dev Dyn 238(6):1226–1248

    Article  Google Scholar 

  • Bely AE, Nyberg KG (2010) Evolution of animal regeneration: re-emergence of a field. Trends Ecol Evol 25(3):161–170

    Article  Google Scholar 

  • Bely AE, Sikes JM (2010) Latent regeneration abilities persist following recent evolutionary loss in asexual annelids. Proc Natl Acad Sci USA 107:1464–1469

    Article  Google Scholar 

  • Birnbaum KD, Sánchez Alvarado A (2008) Slicing across kingdoms: regeneration in plants and animals. Cell 132(4):697–710

    Article  Google Scholar 

  • Brockes JP, Kumar A (2008) Comparative aspects of animal regeneration. Annu Rev Cell Dev Biol 24:525–549

    Article  Google Scholar 

  • Bryant SV, Endo T, Gardiner DM (2002) Vertebrate limb regeneration and the origin of limb stem cells. Int J Dev Biol 46(7):887–896

    Google Scholar 

  • Buckingham M, Montarras D (2008) Skeletal muscle stem cells. Curr Opin Genet Dev 18(4):330–336

    Article  Google Scholar 

  • Burton PM, Finnerty JR (2009) Conserved and novel gene expression between regeneration and asexual fission in Nematostella vectensis. Dev Genes Evol 219(2):79–87

    Article  Google Scholar 

  • Candia Carnevali MD, Bonasoro F (2001) Microscopic overview of crinoid regeneration. Microsc Res Tech 55(6):403–426

    Article  Google Scholar 

  • Carlson MR, Komine Y, Bryant SV, Gardiner DM (2001) Expression of Hoxb13 and Hoxc10 in developing and regenerating Axolotl limbs and tails. Dev Biol 229:396–406

    Article  Google Scholar 

  • Chargé SB, Rudnicki MA (2004) Cellular and molecular regulation of muscle regeneration. Physiol Rev 84(1):209–238

    Article  Google Scholar 

  • Chen JF, Mandel EM, Thomson JM, Wu Q, Callis TE, Hammond SM, Conlon FL, Wang DZ (2006) The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and -differentiation. Nat Genet 38(2):228–233

    Article  Google Scholar 

  • Chera S, Ghila L, Dobretz K, Wenger Y, Bauer C, Buzgariu W, Martinou JC, Galliot B (2009) Apoptotic cells provide an unexpected source of Wnt3 signaling to drive Hydra head regeneration. Dev Cell 17(2):279–289

    Article  Google Scholar 

  • Christen B, Beck CW, Lombardo A, Slack JM (2003) Regeneration-specific expression pattern of three posterior Hox genes. Dev Dyn 226(2):349–355

    Article  Google Scholar 

  • da Silva SM, Gates PB, Brockes JP (2002) The newt ortholog of CD59 is implicated in proximodistal identity during amphibian limb regeneration. Dev Cell 3(4):547–555

    Article  Google Scholar 

  • Daughters RS, Chen Y, Slack JM (2011) Origin of muscle satellite cells in the Xenopus embryo. Development

  • De Angelis L, Berghella L, Coletta M, Lattanzi L, Zanchi M, Cusella-De Angelis MG, Ponzetto C, Cossu G (1999) Skeletal myogenic progenitors originating from embryonic dorsal aorta coexpress endothelial and myogenic markers and contribute to postnatal muscle growth and regeneration. J Cell Biol 147(4):869–878

    Article  Google Scholar 

  • De Mulder K, Pfister D, Kuales G, Egger B, Salvenmoser W, Willems M, Steger J, Fauster K, Micura R, Borgonie G, Ladurner P (2009) Stem cells are differentially regulated during development, regeneration and homeostasis in flatworms. Dev Biol 334:198–212

    Article  Google Scholar 

  • Echeverri K, Tanaka EM (2002) Ectoderm to mesoderm lineage switching during axolotl tail regeneration. Science 298:1993–1996

    Article  Google Scholar 

  • Echeverri K, Clarke JD, Tanaka EM (2001) In vivo imaging indicates muscle fiber dedifferentiation is a major contributor to the regenerating tail blastema. Dev Biol 236:151–164

    Article  Google Scholar 

  • Egar MW (1988) Accessory limb production by nerve-induced cell proliferation. Anat Rec 221(1):550–564

    Article  Google Scholar 

  • Egar M, Singer M (1972) The role of ependyma in spinal cord regeneration in the urodele, Triturus. Exp Neurol 37(2):422–430

    Article  Google Scholar 

  • Endo T, Bryant SV, Gardiner DM (2004) A stepwise model system for limb regeneration. Dev Biol 270:135–145

    Article  Google Scholar 

  • Fraune S, Bosch TC (2010) Why bacteria matter in animal development and evolution. Bioessays 32(7):571–580

    Article  Google Scholar 

  • Fröbius AC, Genikhovich G, Kürn U, Anton-Erxleben F, Bosch TC (2003) Expression of developmental genes during early embryogenesis of Hydra. Dev Genes Evol 213(9):445–455

    Article  Google Scholar 

  • Gabel CV, Antoine F, Chuang CF, Samuel AD, Chang C (2008) Distinct cellular, molecular mechanisms mediate initial axon development, adult-stage axon regeneration in C. elegans. Development 135:1129–1136

    Article  Google Scholar 

  • Galis F, Wagner GP, Jockusch EL (2003) Why is limb regeneration possible in amphibians but not in reptiles, birds, and mammals? Evol Dev 5(2):208–220

    Article  Google Scholar 

  • Galliot B, Miljkovic-Licina M, Chera S (2006) Hydra: a niche for cell and developmental plasticity. Semin Cell Dev Biol 17:492–502

    Article  Google Scholar 

  • Gardiner DM, Blumberg B, Komine Y, Bryant SV (1995) Regulation of HoxA expression in developing and regenerating axolotl limbs. Development 121:1731–1741

    Google Scholar 

  • Garza-Garcia A, Harris R, Esposito D, Gates PB, Driscoll PC (2009) Solution structure and phylogenetics of Prod1, a member of the three-finger protein superfamily implicated in salamander limb regeneration. PLoS One 4(9):e7123

    Article  Google Scholar 

  • Genikhovich G, Kürn U, Hemmrich G, Bosch TC (2006) Discovery of genes expressed in Hydra embryogenesis. Dev Biol 289:466–481

    Article  Google Scholar 

  • Geraudie J, Singer M (1985) Necessity of an adequate nerve supply for regeneration of the amputated pectoral fin in the teleost Fundulus. J Exp Zool 234(3):367–374

    Article  Google Scholar 

  • Gilbert SF (2003) Developmental Biology, 7th edn. Sinauer Associates Inc., Sunderland

    Google Scholar 

  • Gussoni E, Soneoka Y, Strickland CD, Buzney EA, Khan MK, Flint AF, Kunkel LM, Mulligan RC (1999) Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature 401:390–394

    Google Scholar 

  • Janzen FJ, Phillips PC (2006) Exploring the evolution of environmental sex determination, especially in reptiles. J Evol Biol 19:1775–1784

    Article  Google Scholar 

  • Jopling C, Sleep E, Raya M, Martí M, Raya A, Belmonte JC (2010) Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation. Nature 464:606–609

    Article  Google Scholar 

  • Kikuchi K, Holdway JE, Werdich AA, Anderson RM, Fang Y, Egnaczyk GF, Evans T, Macrae CA, Stainier DY, Poss KD (2010) Primary contribution to zebrafish heart regeneration by gata4(+) cardiomyocytes. Nature 464:601–605

    Article  Google Scholar 

  • Kragl M, Knapp D, Nacu E, Khattak S, Maden M, Epperlein HH, Tanaka EM (2009) Cells keep a memory of their tissue origin during axolotl limb regeneration. Nature 460:60–65

    Article  Google Scholar 

  • 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 318:772–777

    Article  Google Scholar 

  • Lepper C, Conway SJ, Fan CM (2009) Adult satellite cells and embryonic muscle progenitors have distinct genetic requirements. Nature 460:627–631

    Article  Google Scholar 

  • Lin G, Chen Y, Slack JM (2007) Regeneration of neural crest derivatives in the Xenopus tadpole tail. BMC Dev Biol 7:56

    Article  Google Scholar 

  • 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 340:145–158

    Article  Google Scholar 

  • Mescher AL (1996) The cellular basis of limb regeneration in urodeles. Int J Dev Biol 40(4):785–795

    Google Scholar 

  • Miljkovic-Licina M, Chera S, Ghila L, Galliot B (2007) Head regeneration in wild-type Hydra requires de novo neurogenesis. Development 134:1191–1201

    Article  Google Scholar 

  • Moore DL, Blackmore MG, Hu Y, Kaestner KH, Bixby JL, Lemmon VP, Goldberg JL (2009) KLF family members regulate intrinsic axon regeneration ability. Science 326:298–301

    Article  Google Scholar 

  • Morgan TH (1898) Experimental studies of the regeneration of Planaria maculata. Archiv fur Entwicklungsmechanik der Organismen 7:364–397

    Article  Google Scholar 

  • Morgan TH (1901) Regeneration. Macmillan, New York

    Google Scholar 

  • Morgan TH (1902) Experimental studies of the internal factors of regeneration in the earthworm. Archiv fur Entwicklungsmechanik der Organismen 14:562–591

    Article  Google Scholar 

  • Muneoka K, Bryant SV (1982) Evidence that patterning mechanisms in developing and regenerating limbs are the same. Nature 298:369–371

    Article  Google Scholar 

  • Muneoka K, Bryant SV (1984) Cellular contribution to supernumerary limbs in the axolotl, Ambystoma mexicanum. Dev Biol 105:166–178

    Article  Google Scholar 

  • Myohara M (2004) Differential tissue development during embryogenesis and regeneration in an Annelid. Dev Dyn 231(2):349–358

    Article  Google Scholar 

  • Myohara M, Yoshida-Noro C, Kobari F, Tochinai S (1999) Fragmenting oligochaete Enchytraeus japonensis: a new material for regeneration study. Dev Growth Differ 41:549–555

    Article  Google Scholar 

  • Newmark PA, Sánchez Alvarado A (2002) Not your father’s planarian: a classic model enters the era of functional genomics. Nat Rev Genet 3(3):210–219

    Article  Google Scholar 

  • Nguyen L, Besson A, Roberts JM, Guillemot F (2006) Coupling cell cycle exit, neuronal differentiation and migration in cortical neurogenesis. Cell Cycle 5:2314–2318

    Article  Google Scholar 

  • Politis PK, Thomaidou D, Matsas R (2008) Coordination of cell cycle exit and differentiation of neuronal progenitors. Cell Cycle 7:691–697

    Article  Google Scholar 

  • Porrello ER, Mahmoud AI, Simpson E, Hill JA, Richardson JA, Olson EN, Sadek HA (2011) Transient regenerative potential of the neonatal mouse heart. Science 331:1078–1080

    Article  Google Scholar 

  • Poss KD (2010) Advances in understanding tissue regenerative capacity and mechanisms in animals. Nat Rev Genet 11(10):710–722

    Article  Google Scholar 

  • Pradeu T (2011) A mixed self: The role of symbiosis in development. Biol Theory. doi:10.1007/s13752-011-0011-5

  • Reginelli AD, Wang YQ, Sassoon D, Muneoka K (1995) Digit tip regeneration correlates with regions of Msx1 (Hox 7) expression in fetal and newborn mice. Development 121:1065–1076

    Google Scholar 

  • Reitzel AM, Burton PM, Krone C, Finnerty JR (2007) Comparison of developmental trajectories in the starlet sea anemone Nematostella vectensis: embryogenesis, regeneration, and two forms of asexual fission. Invertebr Biol 126:99–112

    Article  Google Scholar 

  • Rychel AL, Swalla BJ (2008) Anterior regeneration in the hemichordate Ptychodera flava. Dev Dyn 237:3222–3232

    Article  Google Scholar 

  • Sánchez Alvarado A (2000) Regeneration in the metazoans: why does it happen? Bioessays 22(6):578–590

    Article  Google Scholar 

  • Sánchez Alvarado A (2006) Planarian regeneration: its end is its beginning. Cell 124(2):241–245

    Article  Google Scholar 

  • Sánchez Alvarado A, Tsonis PA (2006) Bridging the regeneration gap: Genetic insights from diverse animal models. Nat Rev Genet 7(11):873–884

    Article  Google Scholar 

  • Seale P, Rudnicki MA (2000) A new look at the origin, function, and “stem-cell” status of muscle satellite cells. Dev Biol 218:115–124

    Article  Google Scholar 

  • Slack JM, Beck CW, Gargioli C, Christen B (2004) Cellular and molecular mechanisms of regeneration in Xenopus. Philos Trans R Soc Lond B 359(1445):745–751

    Article  Google Scholar 

  • Slack JM, Lin G, Chen Y (2008) The Xenopus tadpole: a new model for regeneration research. Cell Mol Life Sci 65(1):54–63

    Article  Google Scholar 

  • Sugimoto K, Gordon SP, Meyerowitz EM (2011) Regeneration in plants and animals: dedifferentiation, transdifferentiation, or just differentiation? Trends Cell Biol 21(4):212–218

    Article  Google Scholar 

  • Sugiura T, Taniguchi Y, Tazaki A, Ueno N, Watanabe K, Mochii M (2004) Differential gene expression between the embryonic tail bud and regenerating larval tail in Xenopus laevis. Dev Growth Differ 46(1):97–105

    Article  Google Scholar 

  • Tajbakhsh S (2009) Skeletal muscle stem cells in developmental versus regenerative myogenesis. J Intern Med 266(4):372–389

    Article  Google Scholar 

  • Tanaka EM (2003) Cell differentiation and cell fate during urodele tail and limb regeneration. Curr Opin Genet Dev 13(5):497–501

    Article  Google Scholar 

  • Théry F (2011) Characterizing animal development with genetic regulatory mechanisms. Biol Theory. doi:10.1007/s13752-011-0004-4

  • Thouveny Y, Tassava RA (1998) Regeneration through phylogenesis. In: Ferretti P, Geraudie J (eds) Cellular, molecular basis of regeneration: from invertebrates to humans. Wiley, New York, pp 9–43

    Google Scholar 

  • Torok MA, Gardiner DM, Shubin NH, Bryant SV (1998) Expression of HoxD genes in developing and regenerating axolotl limbs. Dev Biol 200:225–233

    Article  Google Scholar 

  • Towers M, Tickle C (2009) Growing models of vertebrate limb development. Development 136:179–190

    Article  Google Scholar 

  • Tsonis PA (2007) Regeneration via transdifferentiation: the lens and hair cells. Hear Res 227(1–2):28–31

    Article  Google Scholar 

  • Whitehead GG, Makino S, Lien CL, Keating MT (2005) fgf20 is essential for initiating zebrafish fin regeneration. Science 310:1957–1960

    Article  Google Scholar 

  • Wu Z, Ghosh-Roy A, Yanik MF, Zhang JZ, Jin Y, Chisholm AD (2007) Caenorhabditis elegans neuronal regeneration is influenced by life stage, ephrin signaling, and synaptic branching. Proc Natl Acad Sci USA 104:15132–15137

    Article  Google Scholar 

  • Yanik MF, Cinar H, Cinar HN, Chisholm AD, Jin Y, Ben-Yakar A (2004) Neurosurgery: functional regeneration after laser axotomy. Nature 432:822

    Article  Google Scholar 

  • Yin VP, Poss KD (2008) New regulators of vertebrate appendage regeneration. Curr Opin Genet Dev 18(4):381–386

    Article  Google Scholar 

  • Yin VP, Thomson JM, Thummel R, Hyde DR, Hammond SM, Poss KD (2008) Fgf-dependent depletion of microRNA-133 promotes appendage regeneration in zebrafish. Genes Dev 22(6):728–733

    Article  Google Scholar 

  • Yokoyama H (2008) Initiation of limb regeneration: the critical steps for regenerative capacity. Dev Growth Differ 50(1):13–22

    Article  Google Scholar 

  • Yoshida-Noro C, Tochinai S (2010) Stem cell system in asexual and sexual reproduction of Enchytraeus japonensis (Oligochaeta, Annelida). Dev Growth Differ 52(1):43–55

    Article  Google Scholar 

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Acknowledgments

I am grateful to Pierre Kerner, Lucie Laplane, Michel Morange, Antonine Nicoglou, Thomas Pradeu, and Frédérique Théry for useful discussions and critical reading of this manuscript. My work was supported by the CNRS and the Institut Universitaire de France.

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  1. Institut Jacques Monod, Université Paris Diderot and CNRS, Paris, France

    Michel Vervoort

  2. Institut Universitaire de France, Paris, France

    Michel Vervoort

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Vervoort, M. Regeneration and Development in Animals. Biol Theory 6, 25–35 (2011). https://doi.org/10.1007/s13752-011-0005-3

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