• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of transbhomepageaboutsubmitalertseditorial board
Philos Trans R Soc Lond B Biol Sci. May 29, 2004; 359(1445): 759–763.
PMCID: PMC1693366

Regeneration and the need for simpler model organisms.

Abstract

The problem of regeneration is fundamentally a problem of tissue homeostasis involving the replacement of cells lost to normal 'wear and tear' (cell turnover), and/or injury. This attribute is of particular significance to organisms possessing relatively long lifespans, as maintenance of all body parts and their functional integration is essential for their survival. Because tissue replacement is broadly distributed among multicellular life-forms, and the molecules and mechanisms controlling cellular differentiation are considered ancient evolutionary inventions, it should be possible to gain key molecular insights about regenerative processes through the study of simpler animals. We have chosen to study and develop the freshwater planarian Schmidtea mediterranea as a model system because it is one of the simplest metazoans possessing tissue homeostasis and regeneration, and because it has become relatively easy to molecularly manipulate this organism. The developmental plasticity and longevity of S. mediterranea is in marked contrast to its better-characterized invertebrate cohorts: the fruitfly Drosophila melanogaster and the roundworm Caenorhabditis elegans, both of which have short lifespans and are poor at regenerating tissues. Therefore, planarians present us with new, experimentally accessible contexts in which to study the molecular actions guiding cell fate restriction, differentiation and patterning, each of which is crucial not only for regeneration to occur, but also for the survival and perpetuation of all multicellular organisms.

Full Text

The Full Text of this article is available as a PDF (82K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Barolo Scott, Posakony James W. Three habits of highly effective signaling pathways: principles of transcriptional control by developmental cell signaling. Genes Dev. 2002 May 15;16(10):1167–1181. [PubMed]
  • Boilly B, Cavanaugh KP, Thomas D, Hondermarck H, Bryant SV, Bradshaw RA. Acidic fibroblast growth factor is present in regenerating limb blastemas of axolotls and binds specifically to blastema tissues. Dev Biol. 1991 Jun;145(2):302–310. [PubMed]
  • Brennecke Julius, Hipfner David R, Stark Alexander, Russell Robert B, Cohen Stephen M. bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell. 2003 Apr 4;113(1):25–36. [PubMed]
  • Brockes JP, Kumar A, Velloso CP. Regeneration as an evolutionary variable. J Anat. 2001 Jul-Aug;199(Pt 1-2):3–11. [PMC free article] [PubMed]
  • Cebrià Francesc, Kobayashi Chiyoko, Umesono Yoshihiko, Nakazawa Masumi, Mineta Katsuhiko, Ikeo Kazuho, Gojobori Takashi, Itoh Mari, Taira Masanori, Sánchez Alvarado Alejandro, et al. FGFR-related gene nou-darake restricts brain tissues to the head region of planarians. Nature. 2002 Oct 10;419(6907):620–624. [PubMed]
  • Chervitz SA, Aravind L, Sherlock G, Ball CA, Koonin EV, Dwight SS, Harris MA, Dolinski K, Mohr S, Smith T, et al. Comparison of the complete protein sets of worm and yeast: orthology and divergence. Science. 1998 Dec 11;282(5396):2022–2028. [PMC free article] [PubMed]
  • da Silva Sara Morais, Gates Phillip B, Brockes Jeremy P. The newt ortholog of CD59 is implicated in proximodistal identity during amphibian limb regeneration. Dev Cell. 2002 Oct;3(4):547–555. [PubMed]
  • Force A, Lynch M, Pickett FB, Amores A, Yan YL, Postlethwait J. Preservation of duplicate genes by complementary, degenerative mutations. Genetics. 1999 Apr;151(4):1531–1545. [PMC free article] [PubMed]
  • Fukuchi-Shimogori Tomomi, Grove Elizabeth A. Emx2 patterns the neocortex by regulating FGF positional signaling. Nat Neurosci. 2003 Aug;6(8):825–831. [PubMed]
  • Gerhart J. 1998 Warkany lecture: signaling pathways in development. Teratology. 1999 Oct;60(4):226–239. [PubMed]
  • Godwin AR, Capecchi MR. Hoxc13 mutant mice lack external hair. Genes Dev. 1998 Jan 1;12(1):11–20. [PMC free article] [PubMed]
  • Hartwell LH, Hopfield JJ, Leibler S, Murray AW. From molecular to modular cell biology. Nature. 1999 Dec 2;402(6761 Suppl):C47–C52. [PubMed]
  • Holland PW. Gene duplication: past, present and future. Semin Cell Dev Biol. 1999 Oct;10(5):541–547. [PubMed]
  • Hooper Joan E. Smoothened translates Hedgehog levels into distinct responses. Development. 2003 Sep;130(17):3951–3963. [PubMed]
  • Imokawa Yutaka, Brockes Jeremy P. Selective activation of thrombin is a critical determinant for vertebrate lens regeneration. Curr Biol. 2003 May 13;13(10):877–881. [PubMed]
  • Johnston LA, Edgar BA. Wingless and Notch regulate cell-cycle arrest in the developing Drosophila wing. Nature. 1998 Jul 2;394(6688):82–84. [PubMed]
  • King Nicole, Hittinger Christopher T, Carroll Sean B. Evolution of key cell signaling and adhesion protein families predates animal origins. Science. 2003 Jul 18;301(5631):361–363. [PubMed]
  • Lake JA. Origin of the Metazoa. Proc Natl Acad Sci U S A. 1990 Jan;87(2):763–766. [PMC free article] [PubMed]
  • Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W, et al. Initial sequencing and analysis of the human genome. Nature. 2001 Feb 15;409(6822):860–921. [PubMed]
  • Lee Patricia N, Callaerts Patrick, De Couet Heinz G, Martindale Mark Q. Cephalopod Hox genes and the origin of morphological novelties. Nature. 2003 Aug 28;424(6952):1061–1065. [PubMed]
  • Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993 Dec 3;75(5):843–854. [PubMed]
  • Li X, Noll M. Evolution of distinct developmental functions of three Drosophila genes by acquisition of different cis-regulatory regions. Nature. 1994 Jan 6;367(6458):83–87. [PubMed]
  • McGinnis W. A century of homeosis, a decade of homeoboxes. Genetics. 1994 Jul;137(3):607–611. [PMC free article] [PubMed]
  • Mullen LM, Bryant SV, Torok MA, Blumberg B, Gardiner DM. Nerve dependency of regeneration: the role of Distal-less and FGF signaling in amphibian limb regeneration. Development. 1996 Nov;122(11):3487–3497. [PubMed]
  • Neumann CJ, Cohen SM. Distinct mitogenic and cell fate specification functions of wingless in different regions of the wing. Development. 1996 Jun;122(6):1781–1789. [PubMed]
  • Neumann CJ, Cohen SM. Long-range action of Wingless organizes the dorsal-ventral axis of the Drosophila wing. Development. 1997 Feb;124(4):871–880. [PubMed]
  • Newmark PA, Sánchez Alvarado A. Bromodeoxyuridine specifically labels the regenerative stem cells of planarians. Dev Biol. 2000 Apr 15;220(2):142–153. [PubMed]
  • Newmark Philip A, Sánchez Alvarado Alejandro. Not your father's planarian: a classic model enters the era of functional genomics. Nat Rev Genet. 2002 Mar;3(3):210–219. [PubMed]
  • Odelberg SJ, Kollhoff A, Keating MT. Dedifferentiation of mammalian myotubes induced by msx1. Cell. 2000 Dec 22;103(7):1099–1109. [PubMed]
  • Oviedo Néstor J, Newmark Phillip A, Sánchez Alvarado Alejandro. Allometric scaling and proportion regulation in the freshwater planarian Schmidtea mediterranea. Dev Dyn. 2003 Feb;226(2):326–333. [PubMed]
  • Pecorino LT, Entwistle A, Brockes JP. Activation of a single retinoic acid receptor isoform mediates proximodistal respecification. Curr Biol. 1996 May 1;6(5):563–569. [PubMed]
  • Pinto Daniel, Gregorieff Alex, Begthel Harry, Clevers Hans. Canonical Wnt signals are essential for homeostasis of the intestinal epithelium. Genes Dev. 2003 Jul 15;17(14):1709–1713. [PMC free article] [PubMed]
  • Reinhart BJ, Slack FJ, Basson M, Pasquinelli AE, Bettinger JC, Rougvie AE, Horvitz HR, Ruvkun G. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature. 2000 Feb 24;403(6772):901–906. [PubMed]
  • Robb Sofia M, Sánchez Alvarado Alejandro. Identification of immunological reagents for use in the study of freshwater planarians by means of whole-mount immunofluorescence and confocal microscopy. Genesis. 2002 Apr;32(4):293–298. [PubMed]
  • Rubin GM, Yandell MD, Wortman JR, Gabor Miklos GL, Nelson CR, Hariharan IK, Fortini ME, Li PW, Apweiler R, Fleischmann W, et al. Comparative genomics of the eukaryotes. Science. 2000 Mar 24;287(5461):2204–2215. [PMC free article] [PubMed]
  • Ruvkun G, Hobert O. The taxonomy of developmental control in Caenorhabditis elegans. Science. 1998 Dec 11;282(5396):2033–2041. [PubMed]
  • Sánchez Alvarado A. Regeneration in the metazoans: why does it happen? Bioessays. 2000 Jun;22(6):578–590. [PubMed]
  • Sánchez Alvarado Alejandro. The freshwater planarian Schmidtea mediterranea: embryogenesis, stem cells and regeneration. Curr Opin Genet Dev. 2003 Aug;13(4):438–444. [PubMed]
  • Sánchez Alvarado A, Newmark PA. Double-stranded RNA specifically disrupts gene expression during planarian regeneration. Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5049–5054. [PMC free article] [PubMed]
  • Sánchez Alvarado Alejandro, Newmark Phillip A, Robb Sofia M, Juste Réjeanne. The Schmidtea mediterranea database as a molecular resource for studying platyhelminthes, stem cells and regeneration. Development. 2002 Dec;129(24):5659–5665. [PubMed]
  • Schauer Stephen E, Jacobsen Steven E, Meinke David W, Ray Animesh. DICER-LIKE1: blind men and elephants in Arabidopsis development. Trends Plant Sci. 2002 Nov;7(11):487–491. [PubMed]
  • Schopf JW. Collapse of the Late Proterozoic ecosystem. South Afr J Geol. 1991;94(1):33–43. [PubMed]
  • Steiling Heike, Wüstefeld Torsten, Bugnon Philippe, Brauchle Maria, Fässler Reinhard, Teupser Daniel, Thiery Joachim, Gordon Jeffrey I, Trautwein Christian, Werner Sabine. Fibroblast growth factor receptor signalling is crucial for liver homeostasis and regeneration. Oncogene. 2003 Jul 10;22(28):4380–4388. [PubMed]
  • Telford MJ. Evidence for the derivation of the Drosophila fushi tarazu gene from a Hox gene orthologous to lophotrochozoan Lox5. Curr Biol. 2000 Mar 23;10(6):349–352. [PubMed]
  • von Dassow G, Meir E, Munro EM, Odell GM. The segment polarity network is a robust developmental module. Nature. 2000 Jul 13;406(6792):188–192. [PubMed]

Articles from Philosophical Transactions of the Royal Society B: Biological Sciences are provided here courtesy of The Royal Society

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...