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Wnt gene loss in flatworms

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Abstract

Wnt genes encode secreted glycoproteins that act in cell–cell signalling to regulate a wide array of developmental processes, ranging from cellular differentiation to axial patterning. Discovery that canonical Wnt/β-catenin signalling is responsible for regulating head/tail specification in planarian regeneration has recently highlighted their importance in flatworm (phylum Platyhelminthes) development, but examination of their roles in the complex development of the diverse parasitic groups has yet to be conducted. Here, we characterise Wnt genes in the model tapeworm Hymenolepis microstoma and mine genomic resources of free-living and parasitic species for the presence of Wnts and downstream signalling components. We identify orthologs through a combination of BLAST and phylogenetic analyses, showing that flatworms have a highly reduced and dispersed complement that includes orthologs of only five subfamilies (Wnt1, Wnt2, Wnt4, Wnt5 and Wnt11) and fewer paralogs in parasitic flatworms (5–6) than in planarians (9). All major signalling components are identified, including antagonists and receptors, and key binding domains are intact, indicating that the canonical (Wnt/β-catenin) and non-canonical (planar cell polarity and Wnt/Ca2+) pathways are functional. RNA-Seq data show expression of all Hymenolepis Wnts and most downstream components in adults and larvae with the notable exceptions of wnt1, expressed only in adults, and wnt2 expressed only in larvae. The distribution of Wnt subfamilies in animals corroborates the idea that the last common ancestor of the Cnidaria and Bilateria possessed all contemporary Wnts and highlights the extent of gene loss in flatworms.

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References

  • Adamska M, Degnan SM, Green KM, Adamski M, Craigie A, Larroux C, Degnan BM (2007) Wnt and TGF-β expression in the sponge Amphimedon queenslandica and the origin of metazoan embryonic patterning. PLoS ONE 2:e1031

    Article  PubMed  Google Scholar 

  • Adell T, Salò E, Boutros M, Bartscherer K (2009) Smed-Evi/Wntless is required for B-catenin-dependent and -independent processes during planarian regeneration. Development 136:905–910

    Article  PubMed  CAS  Google Scholar 

  • Baker NE (1987) Molecular cloning of sequences from wingless, a segment polarity gene in Drosophila: the spatial distribution of a transcript in embryos. EMBO J 6:1765–1773

    PubMed  CAS  Google Scholar 

  • Bienz M, Clevers H (2000) Linking colorectal cancer to Wnt signaling. Cell 103:311–320

    Article  PubMed  CAS  Google Scholar 

  • Blair SS (2008) Segmentation in animals. Curr Biol 18:R991–R995

    Article  PubMed  CAS  Google Scholar 

  • Bolognesi R, Farzana L, Fischer TD, Brown SJ (2008) Multiple Wnt genes are required for segmentation in the short-germ embryo of Tribolium castaneum. Curr Biol 18:1624–1629

    Article  PubMed  CAS  Google Scholar 

  • Brooke NM, Garcia-Fernàndez J, Holland PWH (1998) The ParaHox gene cluster is an evolutionary sister of the Hox gene cluster. Nature 392:920–922

    Article  PubMed  CAS  Google Scholar 

  • Broun M (2005) Formation of the head organizer in hydra involves the canonical Wnt pathway. Development 132:2907–2916

    Article  PubMed  CAS  Google Scholar 

  • Cadigan K, Nusse R (1997) Wnt signaling: a common theme in animal development. Gene Dev 11:3286–3305

    Article  PubMed  CAS  Google Scholar 

  • Carver T, Berriman M, Tivey A, Patel C, Bohme U, Barrell BG, Parkhill J, Rajandream M-A (2008) Artemis and ACT: viewing, annotating and comparing sequences stored in a relational database. Bioinformatics 24:2672–2676

    Article  PubMed  CAS  Google Scholar 

  • Chipman AD (2010) Parallel evolution of segmentation by co-option of ancestral gene regulatory networks. BioEssays 32:60–70

    Article  PubMed  CAS  Google Scholar 

  • Cho S-J, Valles Y, Giani VC, Seaver EC, Weisblat DA (2010) Evolutionary dynamics of the Wnt gene family: a lophotrochozoan perspective. Mol Biol Evol 27:1645–1658

    Article  PubMed  CAS  Google Scholar 

  • Coudreuse D, Korswagen HC (2007) The making of Wnt: new insights into Wnt maturation, sorting and secretion. Development 134:3–12

    Article  PubMed  CAS  Google Scholar 

  • Cunningham LJ, Olson PD (2010) Description of Hymenolepis microstoma (Nottingham strain): a classical tapeworm model for research in the genomic era. Parasit Vect 3:123

    Article  Google Scholar 

  • De Robertis EM (2010) Wnt signaling in axial patterning and regeneration: lessons from planaria. Science Signaling 3:pe21

    Article  PubMed  Google Scholar 

  • Dray N, Tessmar-Raible K, Le Gouar M, Vibert L, Christodoulou F, Schipany K, Guillou A, Zantke J, Snyman H, Béhague J, Vervoort M, Arendt D, Balavoine G (2010) Hedgehog signaling reulates segment formation in the annelid Platynereis. Science 329:339–342

    Article  PubMed  CAS  Google Scholar 

  • Drummond AJ, Ashton B, Buxton S, Cheung M, Cooper A, Heled J, Kearse M, Moir R, Stones-Havas S, Sturrock S, Thierer T, Wilson A (2010) Geneious v5.3. Available from http://www.geneious.com.

  • Garriock RJ, Warkman AS, Meadows SM, D'agostino S, Krieg PA (2007) Census of vertebrate Wnt genes: isolation and developmental expression of Xenopus Wnt2, Wnt3, Wnt9a, Wnt9b, Wnt10a, and Wnt16. Dev Dyn 236:1249–1258

    Article  PubMed  CAS  Google Scholar 

  • Gibb S, Zagorska A, Melton K, Tenin G, Vacca I, Trainor P, Maroto M, Dale JK (2009) Interfering with Wnt signalling alters the periodicity of the segmentation clock. Dev Biol 330:21–31

    Article  PubMed  CAS  Google Scholar 

  • Giribet G (2008) Asesmbling the lophotrochozoan (=spiralian) tree of life. Philosophical Trans R Soc Lond B Biol Sci 363:1513–1522

    Article  Google Scholar 

  • Guder C, Philipp I, Lengfield T, Watanabe H, Hobmayer B, Holstein TW (2006) The Wnt code: cnidarians signal the way. Oncogene 25:7450–7460

    Article  PubMed  CAS  Google Scholar 

  • Gurley KA, Rink JC, Alvarado AS (2008) β-catenin defines head versus tail identity during planarian regeneration and homeostasis. Science 319:323–327

    Article  PubMed  CAS  Google Scholar 

  • Gurley KA, Elliott SA, Simakov O, Schmidt HA, Holstein TW, Sanchez Alvarado A (2010) Expression of secreted Wnt pathway components reveals unexpected complexity of the planarian amputation response. Dev Biol 347:24–39

    Article  PubMed  CAS  Google Scholar 

  • Hejnol A, Obst M, Stamatakis A, Ott M, Rouse GW, Edgecomb GD, Martinez P, Baguna J, Bailly X, Jondelius U, Wiens M, Muller WEG, Seaver E, Wheeler WC, Martindale MQ, Giribet G, Dunn CW (2009) Assessing the root of bilaterian animals with scalable phylogenoimc methods. Proc R Soc Biol Sci B 276:4261–4270

    Article  Google Scholar 

  • Iglesias M, Gomez-Skarmeta JL, Salo E, Adell T (2008) Silencing of Smed-betacatenin1 generates radial-like hypercephalized planarians. Development 135:1215–1221

    Article  PubMed  CAS  Google Scholar 

  • Janssen R, Gouar ML, Pechmann M, Poulin F, Bolognesi R, Schwager EE, Hopfen C, Colbourne JK, Budd GE, Brown SJ, Prpic N-M, Kosiol C, Vervoort M, Damen WG, Balavoine G, Mcgregor AP (2010) Conservation, loss, and redeployment of Wnt ligands in protostomes: implications for understanding the evolution of segment formation. BMC Evol Biol 10:374

    Article  PubMed  CAS  Google Scholar 

  • King N, Westbrook M, Young S, Kuo A, Abedin M, Chapman J, Fairclough S, Hellsten U, Isogai Y, Letunic I, Marr M, Pincus D, Putnam N, Rokas A, Wright K, Zuzow R, Dirks W, Good M, Goodstein D, Lemons D, Li W, Lyons J, Morris A, Nichols S, Richter D, Salamov A, Sequencing J, Bork P, Lim W, Manning G, Miller W, McGinnis W, Shapiro H, Tjian R, Grigoriev I, Rokhsar D (2008) The genome of the choanoflagellate Monosiga brevicollis and the origin of metazoans. Nature 451:783–788

    Article  PubMed  CAS  Google Scholar 

  • Koziol U, Lalanne AI, Castillo E (2009) Hox genes in the parasitic Platyhelminthes Mesocestoides corti, Echinococcus multilocularis, and Schistosoma mansoni: evidence for a reduced Hox complement. Biochem Genet 47:100–116

    Article  PubMed  CAS  Google Scholar 

  • Lapébie P, Gazave E, Ereskovsky A, Derelle R, Bézac C, Renard E, Houliston E, Borchiellini C (2009) WNT/β-Catenin signalling and epithelial patterning in the homoscleromorph sponge Oscarella. PLoS ONE 4:e5823

    Article  PubMed  Google Scholar 

  • Lee PN, Pang K, Matus DQ, Martindale MQ (2006) A WNT of things to come: evolution of Wnt signaling and polarity in cnidarians. Semin Cell Dev Biol 17:157–167

    Article  PubMed  Google Scholar 

  • Li H-F, Wang X-B, Jin Y-P, Xia Y-X, Feng X-G, Yang J-M, Qi X-Y, Yuan C-X, Lin J-J (2010) Wnt4, the first member of the Wnt family identified in Schistosoma japonicum, regulates worm development by the canonical pathway. Parasitol Res 107:795–805

    Article  PubMed  Google Scholar 

  • Logan C, Nusse R (2004) The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Bi 20:781–810

    Article  CAS  Google Scholar 

  • Maddison DR, Maddison WP (2005) MacClade 4: analysis of phylogeny and character evolution, 4.08 edn. Sinauer Associates, Sunderland.

  • Martin BL, Kimelman D (2009) Wnt signaling and the evolution of embryonic posterior development. Curr Biol 19:R215–R219

    Article  PubMed  CAS  Google Scholar 

  • Maule AG, Marks NJ (2006) (eds). Parasitic flatworms. Molecular Biology, Biochemistry, Immunology and Physiology. CAB Int., Wallingford

  • McGregor AP, Pechmann M, Schwager EE, Feitosa NM, Kruck S, Aranda M, Damen WGM (2008) Wnt8 is required for growth-zone establishment and development of opisthosomal segments in a spider. Curr Biol 18:1619–1623

    Article  PubMed  CAS  Google Scholar 

  • Miyawaki K, Mito T, Sarashina I, Zhang H, Shinmyo Y, Ohuchi H, Noji S (2004) Involvement of Wingless/Armadillo signaling in the posterior sequential segmentation in the cricket, Gryllus bimaculatus (Orthoptera), as revealed by RNAi analysis. Mech Develop 121:119–130

    Article  CAS  Google Scholar 

  • Mortazavi A, Williams BA, Mccue K, Schaeffer L, Wold B (2008) Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nature Methods 5:621–628

    Article  PubMed  CAS  Google Scholar 

  • Murat S, Hopfen C, McGregor A (2010) The function and evolution of Wnt genes in arthropods. Arth Struct Dev 39:446–452

    Article  CAS  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 32:210–220

    Article  Google Scholar 

  • Nusse R, Varmus H (1992) Wnt Genes. Cell 69:1073–1067

    Article  PubMed  CAS  Google Scholar 

  • Olson P, Zarowiecki M, Kiss F, Brehm K (2011) Cestode genomics—progress and prospects for advancing basic and applied aspects of flatworm biology. Parasit Immunol (in press)

  • Olson PD (2008) Hox genes and the parasitic flatworms: new opportunities, challenges and lessons from the free-living. Parasitol Int 57:8–17

    Article  PubMed  CAS  Google Scholar 

  • Olson PD, Tkach VV (2005) Advances and trends in the molecular systematics of the parasitic Platyhelminthes. Adv Parasitol 60:165–243

    Article  PubMed  Google Scholar 

  • Olson PD, Littlewood DTJ, Bray RA, Mariaux J (2001) Interrelationships and evolution of the tapeworms (Platyhelminthes: Cestoda). Mol Phylogenet Evol 19:443–467

    Article  PubMed  CAS  Google Scholar 

  • Olson PD, Poddubnaya LG, Littlewood DTJ, Scholz T (2008) On the position of Archigetes and its bearing on the early evolution of the tapeworms. J Parasitol 94:898–904

    Article  PubMed  CAS  Google Scholar 

  • Pang K, Ryan JF, Program NCS, Mullikin JC, Baxevanis AD, Martindale MQ (2010) Genomic insights into Wnt signaling in an early diverging metazoan, the ctenophore Mnemiopsis leidyi. EvoDevo 1:10

    Article  PubMed  CAS  Google Scholar 

  • Petersen CP, Reddien PW (2008) Smed2-catenin-1 is required for anteroposterior blastema polarity in planarian regeneration. Science 319:327–330

    Article  PubMed  CAS  Google Scholar 

  • Pires-daSilva A, Sommer RJ (2002) The evoution of signaling pathways in animal development. Nat Rev Genet 4:39–49

    Article  Google Scholar 

  • Polakis P (2000) Wnt signaling and cancer. Genes & Development 14:1837–1851

    CAS  Google Scholar 

  • Prud'homme B, Lartillot N, Balavoine G, Adoutte A, Vervoort M (2002) Phylogenetic analysis of the Wnt gene family. insights from lophotrochozoan members. Curr Biol 12:1395

    Article  PubMed  Google Scholar 

  • Prud'homme B, de Rosa R, Arendt D, Julien J-F, Pajaziti R, Dorresteijn AWC, Adoutte A, Wittbrodt J, Balavoine G (2003) Athropod-like expression patterns of engrailed and wingless in the annelid Platynereis dumerilii suggest a role in segment formation. Curr Biol 13:1876–1881

    Article  PubMed  Google Scholar 

  • Rattner A, Hsieh J, Smallwood P, Gilbert D, Copeland N, Jenkins N, Nathans J (1997) A family of secreted proteins contains homology to the cysteine-rich ligand-binding domain of Frizzled receptors. Proc Natl Acad Sci USA 94:2859–2863

    Article  PubMed  CAS  Google Scholar 

  • Regier J, Shultz J, Zwick A, Hussey A, Ball B, Wetzer R, Martin J, Cunningham C (2010) Arthropod relationships revealed by phylogenomic analysis of nuclear protein-coding sequences. Nature Letters 463:1079–1084

    Article  CAS  Google Scholar 

  • Richards GS, Degnan BM (2009) The dawn of developmental signaling in the Metazoa. Cold Spring Harbor Symposia on Quantitative Biology 74:81–90

    Article  PubMed  CAS  Google Scholar 

  • Ronquist F, Huelsenbeck J (2003) MRBAYES 3: Bayesian phylogenetic inference under mixed models. Bioinformatics 19:1572–1574

    Article  PubMed  CAS  Google Scholar 

  • Rutherford KM, Parkhill J, Crook J, Horsnell T, Rice P, Rajandream M-A, Barrell B (2000) Artemis: seqeunce visualization and annotation. Bioinformatics 16:944–945

    Article  PubMed  CAS  Google Scholar 

  • Ryan JF, Baxevanis AD (2007) Hox, Wnt, and the evolution of the primary body axis: insights from the early-divergent phyla. Biol Direct 2:37

    Article  PubMed  Google Scholar 

  • Salò E (2006) The power of regeneration and the stem-cell kingdom: freshwater planarians (Platyhelminthes). Bioessays 28:546–559

    Article  PubMed  Google Scholar 

  • Salò E, Tauler J, Jimenez E, Bayascas JR, Gonzalez-Linares J, Garcia-Fernàndez J, Baguñà J (2001) Hox and paraHox genes in flatworms: characterization and expression. Am Zool 41:652–663

    Article  Google Scholar 

  • Srivastava M, Begovic E, Chapman J, Putnam NH, Hellsten U, Kawashima T, Kuo A, Mitros T, Salamov A, Carpenter ML, Signorovitch AY, Moreno MA, Kamm K, Grimwood J, Schmutz J, Shapiro H, Grigoriev IV, Buss LW, Schierwater B, Dellaporta SL, Rokhsar DS (2008) The Trichoplax genome and the nature of placozoans. Nature 454:955–960

    Article  PubMed  CAS  Google Scholar 

  • Sullivan JC, Ryan JF, Mullikin JC, Finnerty JR (2007) Conserved and novel Wnt clusters in the basal eumetazoan Nematostella vectensis. Dev Genes Evol 217:235–239

    Article  PubMed  CAS  Google Scholar 

  • Tanaka EM, Weidinger G (2008) Heads or tails: can Wnt tell which one is up? Nature Cell Biol 10:122–124

    Article  PubMed  CAS  Google Scholar 

  • Telford M, Bourlat S, Economou A, Papillon D, Rota-Stabelli O (2008) The evolution of the Ecdysozoa. Phil Trans R Soc B 363:1529–1537

    Article  PubMed  Google Scholar 

  • Umbhauer M, Djiane A, Goisset C, Penzo-Mendez A, Riou J, Boucaut J, Shi D (2000) The C-terminal cytoplasmic Lys-thr-X-X- X-Trp motif in frizzled receptors mediates Wnt/beta- catenin signalling. EMBO 19:4944–4954

    Article  CAS  Google Scholar 

  • van Amerongen R, Nusse R (2009) Towards an integrated view of Wnt signaling in development. Development 136:3205–3214

    Article  PubMed  Google Scholar 

  • Wang Z, Gerstein M, Snyder M (2009) RNA-Seq: a revolutionary tool for transcriptomics. Nature Rev Genet 10:57–63

    Article  PubMed  CAS  Google Scholar 

  • Whelan S, Goldman N (2001) A general emperical model of protein evolution derived from multiple protein families using a maximum-likelihood approach. Mol Biol Evol 18:691–699

    PubMed  CAS  Google Scholar 

  • Wodarz A, Nusse R (1998) Mechanisms of Wnt signaling in development. Ann Rev Cell Dev Biol 14:59–88

    Article  CAS  Google Scholar 

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Acknowledgements

We thank Matt Berriman, Magdalena Zarowiecki and Alejandro Flores-Sanchez for leading the H. microstoma genome initiative at the Wellcome Trust Sanger Institute. Thanks to Natasha Pouchkina-Stantcheva for assistance to NR in the lab, and Lucas Cunningham for help in generating material for WMISH. This work was supported in part by a Biotechnology and Biological Sciences Research Council grant BBG0038151 to PDO.

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  1. Department of Zoology, The Natural History Museum, Cromwell Road, London, SW7 5BD, UK

    Nick Riddiford & Peter D. Olson

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  1. Nick Riddiford
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Correspondence to Peter D. Olson.

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Communicated by D. Weisblat

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Riddiford, N., Olson, P.D. Wnt gene loss in flatworms. Dev Genes Evol 221, 187–197 (2011). https://doi.org/10.1007/s00427-011-0370-8

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