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The Rapid Regenerative Response of a Model Sea Anemone Species Exaiptasia pallida Is Characterised by Tissue Plasticity and Highly Coordinated Cell Communication

Abstract

Regeneration of a limb or tissue can be achieved through multiple different pathways and mechanisms. The sea anemone Exaiptasia pallida has been observed to have excellent regenerative proficiency, but this has not yet been described transcriptionally. In this study, we examined the genetic expression changes during a regenerative timecourse and reported key genes involved in regeneration and wound healing. We found that the major response was an early (within the first 8 h) upregulation of genes involved in cellular movement and cell communication, which likely contribute to a high level of tissue plasticity resulting in the rapid regeneration response observed in this species. We find the immune system was only transcriptionally active in the first 8 h post-amputation and conclude, in accordance with previous literature, that the immune system and regeneration have an inverse relationship. Fifty-nine genes (3.8% of total) differentially expressed during regeneration were identified as having no orthologues in other species, indicating that regeneration in E. pallida may rely on the activation of species-specific novel genes. Additionally, taxonomically restricted novel genes, including species-specific novels, and highly conserved genes were identified throughout the regenerative timecourse, showing that both may work in concert to achieve complete regeneration.

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Data Availability Statement

Raw reads for the Exaiptasia pallida regeneration timecourse are available on the Sequence Read Archive (SRA, NCBI) under BioProject accession number PRJNA507308. Full list of BioSample accession numbers are in Supplementary Table S1. Select gene annotation data is available in the supplementary data, additional gene annotations and read mapping files can be provided upon request. Reads for transcriptomes assembled locally and used in OrthoFinder analysis are on the SRA (accession details are provided in literature as cited) but assembled transcriptome files and annotations can be provided upon request. Raw reads for the three sea anemone transcriptomes generated here (Diadumene lineata, Stichodactyla mertensii and Triactis producta) can be found under BioProject accession number PRJNA507679.

References

  1. Abnave P, Ghigo E (2019) Role of the immune system in regeneration and its dynamic interplay with adult stem cells. Semin Cell Dev Biol 87:160–168

  2. Abrams MJ, Basinger T, Yuan W, Guo CL, Goentoro L (2015) Self-repairing symmetry in jellyfish through mechanically driven reorganization. PNAS 112:E3365–E3373

  3. Albertin CB, Simakov O, Mitros T, Wang ZY, Pungor JR, Edsinger-Gonzales E, Brenner S, Ragsdale CW, Rokhsar DS (2015) The octopus genome and the evolution of cephalopod neural and morphological novelties. Nature 524:220–224

  4. Altincicek B, Vilcinskas A (2008) Comparative analysis of septic injury-inducible genes in phylogenetically distant model organisms of regeneration and stem cell research, the planarian Schmidtea mediterranea and the cnidarian Hydra vulgaris. Front Zool 5:6

  5. Alvarado AS, Tsonis PA (2006) Bridging the regeneration gap: genetic insights from diverse animal models. Nat Rev Genet 7:873–884

  6. Amiel AR, Johnston HT, Nedoncelle K, Warner JF, Ferreira S, Röttinger E (2015) Characterization of morphological and cellular events underlying oral regeneration in the sea anemone, Nematostella vectensis. Int J Mol Sci 16:28449–28471

  7. Ashkenazi A, Fairbrother WJ, Leverson JD, Souers AJ (2017) From basic apoptosis discoveries to advanced selective BCL-2 family inhibitors. Nat Rev Drug Discov 16:273–284

  8. Aufschnaiter R, Zamir EA, Little CD et al (2011) In vivo imaging of basement membrane movement: ECM patterning shapes Hydra polyps. J Cell Sci 124:4027–4038

  9. Babonis LS, Martindale MQ (2017) Phylogenetic evidence for the modular evolution of metazoan signalling pathways. Philos Trans R Soc B 372:20150477

  10. Baumgarten S, Simakov O, Esherick LY, Liew YJ, Lehnert EM, Michell CT, Li Y, Hambleton EA, Guse A, Oates ME, Gough J, Weis VM, Aranda M, Pringle JR, Voolstra CR (2015) The genome of Aiptasia, a sea anemone model for coral symbiosis. PNAS 112:11893–11898

  11. Bhattacharya D, Agrawal S, Aranda M et al (2016) Comparative genomics explains the evolutionary success of reef-forming corals. eLife 5:e13288

  12. Bolger AM, Lohse M, Usadel B (2014) Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30:2114–2120

  13. Bosch TCG (2007) Why polyps regenerate and we don’t: towards a cellular and molecular framework for Hydra regeneration. Dev Biol 303:421–433

  14. Bosch TCG, Augustin R, Anton-Erxleben F, Fraune S, Hemmrich G, Zill H, Rosenstiel P, Jacobs G, Schreiber S, Leippe M, Stanisak M, Grötzinger J, Jung S, Podschun R, Bartels J, Harder J, Schröder JM (2009) Uncovering the evolutionary history of innate immunity: the simple metazoan Hydra uses epithelial cells for host defence. Dev Comp Immunol 33:559–569

  15. Brekhman V, Malik A, Haas B, Sher N, Lotan T (2015) Transcriptome profiling of the dynamic life cycle of the scypohozoan jellyfish Aurelia aurita. BMC Genomics 16:74

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

  17. Brockes JP, Kumar A, Velloso CP (2001) Regeneration as an evolutionary variable. J Anat 199:3–11

  18. Brown T, Rodriguez-Lanetty M (2015) Defending against pathogens—immunological priming and its molecular basis in a sea anemone, cnidarian. Sci Rep 5:17425

  19. Browne EN (1909) The production of new hydranths in Hydra by the insertion of small grafts. J Exp Zool 7:1–23

  20. Bucher M, Wolfowicz I, Voss PA, Hambleton EA, Guse A (2016) Development and symbiosis establishment in the cnidarian endosymbiosis model Aiptasia sp. Sci Rep 6:19867

  21. Buzgariu W, Wenger Y, Tcaciuc N, Catunda-Lemos AP, Galliot B (2018) Impact of cycling cells and cell cycle regulation on Hydra regeneration. Dev Biol 433:240–253

  22. 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 17:279–289

  23. Clayton WS Jr (1985) Pedal laceration by the anemone Aiptasia pallida. Mar Ecol Prog Ser 21:75–80

  24. DuBuc TQ, Traylor-Knowles N, Martindale MQ (2014) Initiating a regenerative response; cellular and molecular features of wound healing in the cnidarian Nematostella vectensis. BMC Biol 12:24

  25. Duffy DJ, Plickert G, Kuenzel T, Tilmann W, Frank U (2010) Wnt signaling promotes oral but suppresses aboral structures in Hydractinia metamorphosis and regeneration. Development 137:3057–3066

  26. Eming SA, Hammerschmidt M, Krieg T, Roers A (2009) Interrelation of immunity and tissue repair or regeneration. Semin Cell Dev Biol 20:517–527

  27. Emms DM, Kelly S (2015) OrthoFinder: solving fundamental biases in whole genome comparisons dramatically improves orthogroup inference accuracy. Genome Biol 16:157

  28. Felsenstein J (1989) PHYLIP—phylogeny inference package (version 3.2). Cladistics 5(2):163–166

  29. Forêt S, Knack B, Houliston E et al (2010) New tricks with old genes: the genetic bases of novel cnidarian traits. Trends Genet 26:154–158

  30. Fowler SJ, Jose S, Zhang X, Deutzmann R, Sarras MP Jr, Boot-Handford RP (2000) Characterization of hydra type IV collagen. Type IV collagen is essential for head regeneration and its expression is up-regulated upon exposure to glucose. J Biol Chem 275:39589–39599

  31. Fukazawa T, Naora Y, Kunieda T, Kubo T (2009) Suppression of the immune response potentiates tadpole tail regeneration during the refractory period. Development 136:2323–2327

  32. Fumagalli MR, Zapperi S, Porta CAML (2018) Regeneration in distantly related species: common strategies and pathways. NPJ Syst Biol Appl 4:5

  33. Garza-Garcia AA, Driscoll PC, Brockes JP (2010) Evidence for the local evolution of mechanisms underlying limb regeneration in salamanders. Integr Comp Biol 50:528–535

  34. Gierer A, Berking S, Bode H, David CN, Flick K, Hansmann G, Schaller H, Trenkner E (1972) Regeneration of Hydra from reaggregated cells. Nat New Biol 239:98–101

  35. Godwin JW, Brockes JP (2006) Regeneration, tissue injury and the immune response. J Anat 209:423–432

  36. Grajales A, Rodríguez E (2016) Elucidating the evolutionary relationships of the Aiptasiidae, a widespread cnidarian–dinoflagellate model system (Cnidaria: Anthozoa: Actiniaria: Metridioidea). Mol Phylogenet Evol 94:252–263

  37. Grawunder D, Hambleton EA, Bucher M, Wolfowicz I, Bechtoldt N, Guse A (2015) Induction of gametogenesis in the cnidarian endosymbiosis model Aiptasia sp. Sci Rep 5:15677

  38. Gurtner GC, Werner S, Barrandon Y, Longaker MT (2008) Wound repair and regeneration. Nature 453:314–321

  39. Haas BJ, Papanicolaou A, Yassour M, Grabherr M, Blood PD, Bowden J, Couger MB, Eccles D, Li B, Lieber M, MacManes M, Ott M, Orvis J, Pochet N, Strozzi F, Weeks N, Westerman R, William T, Dewey CN, Henschel R, LeDuc R, Friedman N, Regev A (2013) De novo transcript sequence reconstruction from RNA-seq using the Trinity platform for reference generation and analysis. Nat Protoc 8:1494–1512

  40. Hobmayer B, Rentzsch F, Kuhn K, Happel CM, von Laue C, Snyder P, Rothbächer U, Holstein TW (2000) WNT signalling molecules act in axis formation in the diploblastic metazoan Hydra. Nature 407:186–189

  41. Holstein TW, Hobmayer E, Technau U (2003) Cnidarians: an evolutionarily conserved model system for regeneration? Dev Dyn 226:257–267

  42. Huang C, Morlighem J-ÉR, Zhou H et al (2016) The transcriptome of the zoanthid Protopalythoa variabilis (Cnidaria, Anthozoa) predicts a basal repertoire of toxin-like and venom-auxiliary polypeptides. Genome Biol Evol 8:3045–3064

  43. Letunic I, Bork P (2018) 20 years of the SMART protein domain annotation resource. Nucleic Acids Res 46:D493–D496

  44. Letunic I, Doerks T, Bork P (2015) SMART: recent updates, new developments and status in 2015. Nucleic Acids Res 43:D257–D260

  45. Liu S-Y, Selck C, Friedrich B et al (2013) Reactivating head regrowth in a regeneration-deficient planarian species. Nature 500:81–84

  46. Manuel M (2009) Early evolution of symmetry and polarity in metazoan body plans. Comptes Rendus Biologies 332:184–209

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

  48. Miller DJ, Ball EE, Technau U (2005) Cnidarians and ancestral genetic complexity in the animal kingdom. Trends Genet 21:536–539

  49. Morgan TH (1901) Regeneration in the egg, embryo, and adult. Am Nat 35:949–973

  50. Oakley CA, Ameismeier MF, Peng L, Weis VM, Grossman AR, Davy SK (2016) Symbiosis induces widespread changes in the proteome of the model cnidarian Aiptasia. Cell Microbiol 18:1009–1023

  51. Passamaneck YJ, Martindale MQ (2012) Cell proliferation is necessary for the regeneration of oral structures in the anthozoan cnidarian Nematostella vectensis. BMC Dev Biol 12:34

  52. Peiris TH, Hoyer KK, Oviedo NJ (2014) Innate immune system and tissue regeneration in planarians: an area ripe for exploration. Semin Immunol 26:295–302

  53. Petersen CP, Reddien PW (2011) Polarized notum activation at wounds inhibits Wnt function to promote planarian head regeneration. Science 332:852–855

  54. Petersen HO, Höger SK, Looso M et al (2015) A comprehensive transcriptomic and proteomic analysis of Hydra head regeneration. Mol Biol Evol 32:1928–1947

  55. Poole AZ, Kitchen SA, Weis VM (2016) The role of complement in cnidarian-dinoflagellate symbiosis and immune challenge in the sea anemone Aiptasia pallida. Front Microbiol 7:519

  56. Poole AZ, Weis VM (2014) TIR-domain-containing protein repertoire of nine anthozoan species reveals coral–specific expansions and uncharacterized proteins. Dev Comp Immunol 46:480–488

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

  58. Putnam NH, Srivastava M, Hellsten U, Dirks B, Chapman J, Salamov A, Terry A, Shapiro H, Lindquist E, Kapitonov VV, Jurka J, Genikhovich G, Grigoriev IV, Lucas SM, Steele RE, Finnerty JR, Technau U, Martindale MQ, Rokhsar DS (2007) Sea anemone genome reveals ancestral eumetazoan gene repertoire and genomic organization. Science 317:86–94

  59. Robinson MD, McCarthy DJ, Smyth GK (2010) edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26:139–140

  60. Rodríguez E, Barbeitos MS, Brugler MR, Crowley LM, Grajales A, Gusmão L, Häussermann V, Reft A, Daly M (2014) Hidden among sea anemones: the first comprehensive phylogenetic reconstruction of the order Actiniaria (Cnidaria, Anthozoa, Hexacorallia) reveals a novel group of hexacorals. PLoS One 9:e96998

  61. Roesel CL, Vollmer SV (2019) Differential gene expression analysis of symbiotic and aposymbiotic Exaiptasia anemones under immune challenge with Vibrio coralliilyticus. Ecol Evol 9:8279–8293

  62. Schaffer AA, Bazarsky M, Levy K, Chalifa-Caspi V, Gat U (2016) A transcriptional time-course analysis of oral vs. aboral whole-body regeneration in the sea anemone Nematostella vectensis. BMC Genomics 17:718

  63. Shick JM (2012) A functional biology of sea anemones. Chapman & Hall, London

  64. Shoguchi E, Shinzato C, Kawashima T, Gyoja F, Mungpakdee S, Koyanagi R, Takeuchi T, Hisata K, Tanaka M, Fujiwara M, Hamada M, Seidi A, Fujie M, Usami T, Goto H, Yamasaki S, Arakaki N, Suzuki Y, Sugano S, Toyoda A, Kuroki Y, Fujiyama A, Medina M, Coffroth MA, Bhattacharya D, Satoh N (2013) Draft assembly of the Symbiodinium minutum nuclear genome reveals dinoflagellate gene structure. Curr Biol 23:1399–1408

  65. Singer II (1974) An electron microscopic and autoradiographic study of mesogleal organization and collagen synthesis in the sea anemone Aiptasia diaphana. Cell Tissue Res 149:537–554

  66. Singer II (1971) Tentacular and oral-disc regeneration in the sea anemone, Aiptasia diaphana III. J Embryol Exp Morphol 26:253–270

  67. Singer II, Palmer JD (1969) Tentacular and oral-disc regeneration in the sea anemone, Aiptasia diaphana II. Naturwissenschaften 56:574–575

  68. Sinigaglia C, Busengdal H, Leclère L, Technau U, Rentzsch F (2013) The bilaterian head patterning gene six3/6 controls aboral domain development in a cnidarian. PLoS Biol 11:e1001488

  69. 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

  70. Srivastava M, Simakov O, Chapman J et al (2010) The Amphimedon queenslandica genome and the evolution of animal complexity. Nature 466:720–726

  71. Stewart ZK, Pavasovic A, Hock DH, Prentis PJ (2017) Transcriptomic investigation of wound healing and regeneration in the cnidarian Calliactis polypus. Sci Rep 7:41458

  72. Surm JM, Smith HL, Madio B, Undheim EAB, King GF, Hamilton BR, van der Burg C, Pavasovic A, Prentis PJ (2019) A process of convergent amplification and tissue-specific expression dominates the evolution of toxin and toxin-like genes in sea anemones. Mol Ecol 28:2272–2289

  73. Tanaka EM, Reddien PW (2011) The cellular basis for animal regeneration. Dev Cell 21:172–185

  74. Tiozzo S, Copley RR (2015) Reconsidering regeneration in metazoans: an evo-devo approach. Front Ecol Evol 3:67

  75. Trembley A (1744) Mémoires pour servir a l’histoire d’un genre de polypes d’eau douce, a bras en forme de cornes. J. and H. Verbeek

  76. van de Water JA, Ainsworth TD, Leggat W et al (2015) The coral immune response facilitates protection against microbes during tissue regeneration. Mol Ecol 24:3390–3404

  77. van der Burg CA, Prentis PJ, Surm JM, Pavasovic A (2016) Insights into the innate immunome of actiniarians using a comparative genomic approach. BMC Genomics 17:850

  78. Wang X, Liew YJ, Li Y, Zoccola D, Tambutte S, Aranda M (2017) Draft genomes of the corallimorpharians Amplexidiscus fenestrafer and Discosoma sp. Mol Ecol Resour 17:e187–e195

  79. Warner JF, Amiel AR, Johnston H, Röttinger E (2019) Regeneration is a partial redeployment of the embryonic gene network. bioRxiv 658930

  80. Young J (1974) The nature of tissue regeneration after wounding in the sea anemone Calliactis parasitica (Couch). J Mar Biol Assoc UK 54:599–617

  81. Yum LK, Baumgarten S, Röthig T, Roder C, Roik A, Michell C, Voolstra CR (2017) Transcriptomes and expression profiling of deep-sea corals from the Red Sea provide insight into the biology of azooxanthellate corals. Sci Rep 7:6442

  82. Zhang G, Fang X, Guo X, Li L, Luo R, Xu F, Yang P, Zhang L, Wang X, Qi H, Xiong Z, Que H, Xie Y, Holland PW, Paps J, Zhu Y, Wu F, Chen Y, Wang J, Peng C, Meng J, Yang L, Liu J, Wen B, Zhang N, Huang Z, Zhu Q, Feng Y, Mount A, Hedgecock D, Xu Z, Liu Y, Domazet-Lošo T, du Y, Sun X, Zhang S, Liu B, Cheng P, Jiang X, Li J, Fan D, Wang W, Fu W, Wang T, Wang B, Zhang J, Peng Z, Li Y, Li N, Wang J, Chen M, He Y, Tan F, Song X, Zheng Q, Huang R, Yang H, du X, Chen L, Yang M, Gaffney PM, Wang S, Luo L, She Z, Ming Y, Huang W, Zhang S, Huang B, Zhang Y, Qu T, Ni P, Miao G, Wang J, Wang Q, Steinberg CE, Wang H, Li N, Qian L, Zhang G, Li Y, Yang H, Liu X, Wang J, Yin Y, Wang J (2012) The oyster genome reveals stress adaptation and complexity of shell formation. Nature 490:49–54

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Acknowledgements

Computational resources used in this work were provided by the HPC (High Performance Computing). Lab space was provided by MGRF (Molecular Genomics Research Facility) and technical support was provided by Vincent Chand and Sahana Manoli at MGRF at Queensland University of Technology, Brisbane, Australia. The authors would like to thank the members of the Prentis lab group, in particular Jessica O’Callaghan, for their insights and support. The authors would also like to thank the marine lab crew at QUT for their continual help with care and maintenance of the marine animals. Special thanks goes to Dr. Libby Liggins (Massey University, New Zealand) for providing the D. lineata sample.

Funding

The authors would like to acknowledge the Institute of Health and Biomedical Innovation (IHBI) for providing funding for the generation of raw reads for this project.

Author information

C.V.D.B., A.P., J.S. and P.P. conceived and designed the research; C.V.D.B., J.S. and H.S. performed the experiments; C.V.D.B and H.S. sequenced and assembled the transcriptomes; C.V.D.B analysed the data; C.V.D.B., A.P., E.G., E.P., J.S., T.W. and P.P. interpreted the results of experiments; C.V.D.B. prepared the figures; C.V.D.B. and P.P. drafted the manuscript; and C.V.D.B., A.P., E.G., E.P., J.S., H.S., T.W. and P.P. edited, revised and approved the final version of the manuscript.

Correspondence to Chloé A. van der Burg.

Ethics declarations

This project did not require animal ethics approval. Sample collection for sea anemones collected in Australia (all sea anemone datasets generated here, except for Diadumene lineata) was authorised under the Fisheries Act 1994 (General Fisheries Permit), permit number: 166312. Sample collection for Diadumene lineata, which was collected in New Zealand, was authorised under the Ministry for Primary Industries Special Permit (632).

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The authors declare that they have no conflict of interest.

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van der Burg, C.A., Pavasovic, A., Gilding, E.K. et al. The Rapid Regenerative Response of a Model Sea Anemone Species Exaiptasia pallida Is Characterised by Tissue Plasticity and Highly Coordinated Cell Communication. Mar Biotechnol (2020). https://doi.org/10.1007/s10126-020-09951-w

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Keywords

  • Cnidaria
  • Transcriptomics
  • Timecourse
  • Immune system
  • Evolution
  • QuantSeq