activin-2 is required for regeneration of polarity on the planarian anterior-posterior axis


Autoři: Jennifer K. Cloutier aff001;  Conor L. McMann aff001;  Isaac M. Oderberg aff001;  Peter W. Reddien aff001
Působiště autorů: Whitehead Institute for Biomedical Research, Cambridge, MA, United States of America aff001;  Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, United States of America aff002;  Howard Hughes Medical Institute, Chevy Chase, MD, United States of America aff003;  Harvard/MIT MD-PhD, Harvard Medical School, Boston, MA, United States of America aff004
Vyšlo v časopise: activin-2 is required for regeneration of polarity on the planarian anterior-posterior axis. PLoS Genet 17(3): e1009466. doi:10.1371/journal.pgen.1009466
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1009466

Souhrn

Planarians are flatworms and can perform whole-body regeneration. This ability involves a mechanism to distinguish between anterior-facing wounds that require head regeneration and posterior-facing wounds that require tail regeneration. How this head-tail regeneration polarity decision is made is studied to identify principles underlying tissue-identity specification in regeneration. We report that inhibition of activin-2, which encodes an Activin-like signaling ligand, resulted in the regeneration of ectopic posterior-facing heads following amputation. During tissue turnover in uninjured planarians, positional information is constitutively expressed in muscle to maintain proper patterning. Positional information includes Wnts expressed in the posterior and Wnt antagonists expressed in the anterior. Upon amputation, several wound-induced genes promote re-establishment of positional information. The head-versus-tail regeneration decision involves preferential wound induction of the Wnt antagonist notum at anterior-facing over posterior-facing wounds. Asymmetric activation of notum represents the earliest known molecular distinction between head and tail regeneration, yet how it occurs is unknown. activin-2 RNAi animals displayed symmetric wound-induced activation of notum at anterior- and posterior-facing wounds, providing a molecular explanation for their ectopic posterior-head phenotype. activin-2 RNAi animals also displayed anterior-posterior (AP) axis splitting, with two heads appearing in anterior blastemas, and various combinations of heads and tails appearing in posterior blastemas. This was associated with ectopic nucleation of anterior poles, which are head-tip muscle cells that facilitate AP and medial-lateral (ML) pattern at posterior-facing wounds. These findings reveal a role for Activin signaling in determining the outcome of AP-axis-patterning events that are specific to regeneration.

Klíčová slova:

Gene expression – Head regeneration – Muscle cells – Planarians – Regeneration – RNA interference – Wnt signaling cascade – Surgical amputation


Zdroje

1. Randolph H. Observations and experiments on regeneration in planarians. Arch Entw Mech Org. 1897;5:352–72.

2. Morgan TH. Experimental studies of the regeneration of Planaria maculata. Arch Entw Mech Org. 1898;7:364–97.

3. Reddien PW. The Cellular and Molecular Basis for Planarian Regeneration. Cell. 2018;175(2):327–45. doi: 10.1016/j.cell.2018.09.021 30290140

4. Witchley JN, Mayer M, Wagner DE, Owen JH, Reddien PW. Muscle cells provide instructions for planarian regeneration. Cell Reports. 2013;4(4):633–41. doi: 10.1016/j.celrep.2013.07.022 23954785

5. Petersen CP, Reddien PW. Smed-betacatenin-1 is required for anteroposterior blastema polarity in planarian regeneration. Science. 2008;319(5861):327–30. doi: 10.1126/science.1149943 18063755

6. Gurley KA, Rink JC, Sánchez Alvarado A. Beta-catenin defines head versus tail identity during planarian regeneration and homeostasis. Science. 2008;319(5861):323–7. doi: 10.1126/science.1150029 18063757

7. Iglesias M, Gomez-Skarmeta JL, Saló E, Adell T. Silencing of Smed-betacatenin1 generates radial-like hypercephalized planarians. Development. 2008;135(7):1215–21. doi: 10.1242/dev.020289 18287199

8. Adell T, Saló E, Boutros M, Bartscherer K. Smed-Evi/Wntless is required for beta-catenin-dependent and -independent processes during planarian regeneration. Development. 2009;136(6):905–10. doi: 10.1242/dev.033761 19211673

9. Petersen CP, Reddien PW. A wound-induced Wnt expression program controls planarian regeneration polarity. Proc Natl Acad Sci U S A. 2009;106(40):17061–6. doi: 10.1073/pnas.0906823106 19805089

10. Gurley KA, Elliott SA, Simakov O, Schmidt HA, Holstein TW, Sánchez Alvarado A. Expression of secreted Wnt pathway components reveals unexpected complexity of the planarian amputation response. Dev Biol. 2010;347(1):24–39. doi: 10.1016/j.ydbio.2010.08.007 20707997

11. Almuedo-Castillo M, Saló E, Adell T. Dishevelled is essential for neural connectivity and planar cell polarity in planarians. Proc Natl Acad Sci U S A. 2011;108(7):2813–8. doi: 10.1073/pnas.1012090108 21282632

12. Petersen CP, Reddien PW. Polarized notum activation at wounds inhibits Wnt function to promote planarian head regeneration. Science. 2011;332(6031):852–5. doi: 10.1126/science.1202143 21566195

13. Reuter H, Marz M, Vogg MC, Eccles D, Grifol-Boldu L, Wehner D, et al. Beta-catenin-dependent control of positional information along the AP body axis in planarians involves a teashirt family member. Cell Rep. 2015;10(2):253–65. doi: 10.1016/j.celrep.2014.12.018 25558068

14. Owen JH, Wagner DE, Chen CC, Petersen CP, Reddien PW. teashirt is required for head-versus-tail regeneration polarity in planarians. Development. 2015;142(6):1062–72. doi: 10.1242/dev.119685 25725068

15. Scimone ML, Cote LE, Rogers T, Reddien PW. Two FGFRL-Wnt circuits organize the planarian anteroposterior axis. Elife. 2016;5. doi: 10.7554/eLife.12845 27063937

16. Lander R, Petersen CP. Wnt, Ptk7, and FGFRL expression gradients control trunk positional identity in planarian regeneration. Elife. 2016;5.

17. Sureda-Gomez M, Martin-Duran JM, Adell T. Localization of planarian beta-CATENIN-1 reveals multiple roles during anterior-posterior regeneration and organogenesis. Development. 2016;143(22):4149–60. doi: 10.1242/dev.135152 27737903

18. Stuckemann T, Cleland JP, Werner S, Thi-Kim Vu H, Bayersdorf R, Liu SY, et al. Antagonistic Self-Organizing Patterning Systems Control Maintenance and Regeneration of the Anteroposterior Axis in Planarians. Dev Cell. 2017;40(3):248–63 e4. doi: 10.1016/j.devcel.2016.12.024 28171748

19. Wurtzel O, Cote LE, Poirier A, Satija R, Regev A, Reddien PW. A Generic and Cell-Type-Specific Wound Response Precedes Regeneration in Planarians. Dev Cell. 2015;35(5):632–45. doi: 10.1016/j.devcel.2015.11.004 26651295

20. Wenemoser D, Lapan SW, Wilkinson AW, Bell GW, Reddien PW. A molecular wound response program associated with regeneration initiation in planarians. Genes & Development. 2012;26(9):988–1002. doi: 10.1101/gad.187377.112 22549959

21. Kakugawa S, Langton PF, Zebisch M, Howell S, Chang TH, Liu Y, et al. Notum deacylates Wnt proteins to suppress signalling activity. Nature. 2015;519(7542):187–92. doi: 10.1038/nature14259 25731175

22. Scimone ML, Cote LE, Reddien PW. Orthogonal muscle fibres have different instructive roles in planarian regeneration. Nature. 2017;551(7682):623–8. doi: 10.1038/nature24660 29168507

23. Scimone ML, Lapan SW, Reddien PW. A forkhead transcription factor is wound-induced at the planarian midline and required for anterior pole regeneration. PLoS genetics. 2014;10(1):e1003999. doi: 10.1371/journal.pgen.1003999 24415944

24. Vogg MC, Owlarn S, Perez Rico YA, Xie J, Suzuki Y, Gentile L, et al. Stem cell-dependent formation of a functional anterior regeneration pole in planarians requires Zic and Forkhead transcription factors. Developmental Biology. 2014;390(2):136–48. doi: 10.1016/j.ydbio.2014.03.016 24704339

25. Vasquez-Doorman C, Petersen CP. zic-1 Expression in planarian neoblasts after injury controls anterior pole regeneration. PLoS genetics. 2014;10(7):e1004452. doi: 10.1371/journal.pgen.1004452 24992682

26. Oderberg IM, Li DJ, Scimone ML, Gavino MA, Reddien PW. Landmarks in Existing Tissue at Wounds Are Utilized to Generate Pattern in Regenerating Tissue. Curr Biol. 2017;27(5):733–42. doi: 10.1016/j.cub.2017.01.024 28216315

27. Roberts-Galbraith RH, Newmark PA. Follistatin antagonizes activin signaling and acts with notum to direct planarian head regeneration. Proc Natl Acad Sci U S A. 2013;110(4):1363–8. doi: 10.1073/pnas.1214053110 23297191

28. Gavino MA, Wenemoser D, Wang IE, Reddien PW. Tissue absence initiates regeneration through Follistatin-mediated inhibition of Activin signaling. eLife. 2013;2:e00247. doi: 10.7554/eLife.00247 24040508

29. Gehrke AR, Neverett E, Luo YJ, Brandt A, Ricci L, Hulett RE, et al. Acoel genome reveals the regulatory landscape of whole-body regeneration. Science. 2019;363(6432). doi: 10.1126/science.aau6173 30872491

30. Tewari AG, Stern SR, Oderberg IM, Reddien PW. Cellular and Molecular Responses Unique to Major Injury Are Dispensable for Planarian Regeneration. Cell Rep. 2018;25(9):2577–90 e3. doi: 10.1016/j.celrep.2018.11.004 30485821

31. Nakamura T, Takio K, Eto Y, Shibai H, Titani K, Sugino H. Activin-binding protein from rat ovary is follistatin. Science. 1990;247(4944):836–8. doi: 10.1126/science.2106159 2106159

32. Hemmati-Brivanlou A, Kelly OG, Melton DA. Follistatin, an antagonist of activin, is expressed in the Spemann organizer and displays direct neuralizing activity. Cell. 1994;77(2):283–95. doi: 10.1016/0092-8674(94)90320-4 8168135

33. Hill JJ, Davies MV, Pearson AA, Wang JH, Hewick RM, Wolfman NM, et al. The myostatin propeptide and the follistatin-related gene are inhibitory binding proteins of myostatin in normal serum. J Biol Chem. 2002;277(43):40735–41. doi: 10.1074/jbc.M206379200 12194980

34. Gilson H, Schakman O, Kalista S, Lause P, Tsuchida K, Thissen JP. Follistatin induces muscle hypertrophy through satellite cell proliferation and inhibition of both myostatin and activin. Am J Physiol Endocrinol Metab. 2009;297(1):E157–64. doi: 10.1152/ajpendo.00193.2009 19435857

35. Arnold CP, Benham-Pyle BW, Lange JJ, Wood CJ, Sánchez Alvarado A. Wnt and TGFbeta coordinate growth and patterning to regulate size-dependent behaviour. Nature. 2019;572(7771):655–9. doi: 10.1038/s41586-019-1478-7 31413361

36. Kenny NJ, Namigai EK, Dearden PK, Hui JH, Grande C, Shimeld SM. The Lophotrochozoan TGF-beta signalling cassette—diversification and conservation in a key signalling pathway. Int J Dev Biol. 2014;58(6–8):533–49. doi: 10.1387/ijdb.140080nk 25690968

37. Wankell M, Kaesler S, Zhang YQ, Florence C, Werner S, Duan R. The activin binding proteins follistatin and follistatin-related protein are differentially regulated in vitro and during cutaneous wound repair. J Endocrinol. 2001;171(3):385–95. doi: 10.1677/joe.0.1710385 11739004

38. Jazwinska A, Badakov R, Keating MT. Activin-betaA signaling is required for zebrafish fin regeneration. Curr Biol. 2007;17(16):1390–5. doi: 10.1016/j.cub.2007.07.019 17683938

39. Dogra D, Ahuja S, Kim HT, Rasouli SJ, Stainier DYR, Reischauer S. Opposite effects of Activin type 2 receptor ligands on cardiomyocyte proliferation during development and repair. Nat Commun. 2017;8(1):1902. doi: 10.1038/s41467-017-01950-1 29196619

40. Edgecombe GD, Giribet G, Dunn CW, Henjol A, M. Kristensen RM. Rouse GW, et al. Higher-level metazoan relationships: recent progress and remaining questions. Organisms Diversity & Evol. 2011;11(2):151–72.

41. Lee SJ, Reed LA, Davies MV, Girgenrath S, Goad ME, Tomkinson KN, et al. Regulation of muscle growth by multiple ligands signaling through activin type II receptors. Proc Natl Acad Sci U S A. 2005;102(50):18117–22. doi: 10.1073/pnas.0505996102 16330774

42. Massague J, Blain SW, Lo RS. TGFbeta signaling in growth control, cancer, and heritable disorders. Cell. 2000;103(2):295–309. doi: 10.1016/s0092-8674(00)00121-5 11057902

43. Morvan F, Rondeau JM, Zou C, Minetti G, Scheufler C, Scharenberg M, et al. Blockade of activin type II receptors with a dual anti-ActRIIA/IIB antibody is critical to promote maximal skeletal muscle hypertrophy. Proc Natl Acad Sci U S A. 2017;114(47):12448–53. doi: 10.1073/pnas.1707925114 29109273

44. Newfeld SJ, Wisotzkey RG, Kumar S. Molecular evolution of a developmental pathway: phylogenetic analyses of transforming growth factor-beta family ligands, receptors and Smad signal transducers. Genetics. 1999;152(2):783–95. 10353918

45. Kahlem P, Newfeld SJ. Informatics approaches to understanding TGFbeta pathway regulation. Development. 2009;136(22):3729–40. doi: 10.1242/dev.030320 19855015

46. Munz B, Hubner G, Tretter Y, Alzheimer C, Werner S. A novel role of activin in inflammation and repair. J Endocrinol. 1999;161(2):187–93. doi: 10.1677/joe.0.1610187 10320815

47. Song W, Cheng D, Hong S, Sappe B, Hu Y, Wei N, et al. Midgut-Derived Activin Regulates Glucagon-like Action in the Fat Body and Glycemic Control. Cell Metab. 2017;25(2):386–99. doi: 10.1016/j.cmet.2017.01.002 28178568

48. Song W, Owusu-Ansah E, Hu Y, Cheng D, Ni X, Zirin J, et al. Activin signaling mediates muscle-to-adipose communication in a mitochondria dysfunction-associated obesity model. Proc Natl Acad Sci U S A. 2017;114(32):8596–601. doi: 10.1073/pnas.1708037114 28739899

49. Fincher CT, Wurtzel O, de Hoog T, Kravarik KM, Reddien PW. Cell type transcriptome atlas for the planarian Schmidtea mediterranea. Science. 2018;360(6391). doi: 10.1126/science.aaq1736 29674431

50. Scimone ML, Wurtzel O, Malecek K, Fincher CT, Oderberg IM, Kravarik KM, et al. foxF-1 Controls Specification of Non-body Wall Muscle and Phagocytic Cells in Planarians. Curr Biol. 2018;28(23):3787–801 e6. doi: 10.1016/j.cub.2018.10.030 30471994

51. Baguñà J, Saló E, Auladell C. Regeneration and pattern formation in planarians. III. Evidence that neoblasts are totipotent stem cells and the source of blastema cells. Development. 1989;107:77–86.

52. Newmark P, Sánchez Alvarado A. Bromodeoxyuridine specifically labels the regenerative stem cells of planarians. Dev Biol. 2000;220(2):142–53. doi: 10.1006/dbio.2000.9645 10753506

53. Reddien PW, Oviedo NJ, Jennings JR, Jenkin JC, Sánchez Alvarado A. SMEDWI-2 is a PIWI-like protein that regulates planarian stem cells. Science. 2005;310:1327–30. doi: 10.1126/science.1116110 16311336

54. Eisenhoffer GT, Kang H, Sánchez Alvarado A. Molecular analysis of stem cells and their descendants during cell turnover and regeneration in the planarian Schmidtea mediterranea. Cell Stem Cell. 2008;3(3):327–39. doi: 10.1016/j.stem.2008.07.002 18786419

55. Bardeen CR, Baetjer FH. The inhibitive action of the Roentgen rays on regeneration in planarians. J Exp Zool. 1904;1:191–5.

56. Dubois F. Démostration de la migration des cellules de régénération des planaries par le méthode des greffes et des irradiations combinées. Séance. 1948:1316–8.

57. Hayashi T, Motoishi M, Yazawa S, Itomi K, Tanegashima C, Nishimura O, et al. A LIM-homeobox gene is required for differentiation of Wnt-expressing cells at the posterior end of the planarian body. Development. 2011;138(17):3679–88. doi: 10.1242/dev.060194 21828095

58. Schad EG, Petersen CP. STRIPAK Limits Stem Cell Differentiation of a WNT Signaling Center to Control Planarian Axis Scaling. Curr Biol. 2020;30(2):254–63 e2. doi: 10.1016/j.cub.2019.11.068 31928872

59. Wurtzel O, Oderberg IM, Reddien PW. Planarian Epidermal Stem Cells Respond to Positional Cues to Promote Cell-Type Diversity. Dev Cell. 2017;40(5):491–504 e5. doi: 10.1016/j.devcel.2017.02.008 28292427

60. Rink JC, Gurley KA, Elliott SA, Sánchez Alvarado A. Planarian Hh signaling regulates regeneration polarity and links Hh pathway evolution to cilia. Science. 2009;326(5958):1406–10. doi: 10.1126/science.1178712 19933103

61. Yazawa S, Umesono Y, Hayashi T, Tarui H, Agata K. Planarian Hedgehog/Patched establishes anterior-posterior polarity by regulating Wnt signaling. Proc Natl Acad Sci U S A. 2009;106(52):22329–34. doi: 10.1073/pnas.0907464106 20018728

62. Glazer AM, Wilkinson AW, Backer CB, Lapan SW, Gutzman JH, Cheeseman IM, et al. The Zn finger protein Iguana impacts Hedgehog signaling by promoting ciliogenesis. Dev Biol. 2010;337(1):148–56. doi: 10.1016/j.ydbio.2009.10.025 19852954

63. DeRobertis E, Sasai Y. A common plan for dorsoventral patterning in Bilateria. Nature. 1996;380(6569):37–40. doi: 10.1038/380037a0 8598900

64. Orii H, Watanabe K. Bone morphogenetic protein is required for dorso-ventral patterning in the planarian Dugesia japonica. Dev Growth Differ. 2007;49(4):345–9. doi: 10.1111/j.1440-169X.2007.00931.x 17501910

65. Molina MD, Saló E, Cebria F. The BMP pathway is essential for re-specification and maintenance of the dorsoventral axis in regenerating and intact planarians. Dev Biol. 2007;311(1):79–94. doi: 10.1016/j.ydbio.2007.08.019 17905225

66. Reddien PW, Bermange AL, Kicza AM, Sánchez Alvarado A. BMP signaling regulates the dorsal planarian midline and is needed for asymmetric regeneration. Development. 2007;134(22):4043–51. doi: 10.1242/dev.007138 17942485

67. Erter CE, Solnica-Krezel L, Wright CV. Zebrafish nodal-related 2 encodes an early mesendodermal inducer signaling from the extraembryonic yolk syncytial layer. Dev Biol. 1998;204(2):361–72. doi: 10.1006/dbio.1998.9097 9882476

68. Agius E, Oelgeschlager M, Wessely O, Kemp C, De Robertis EM. Endodermal Nodal-related signals and mesoderm induction in Xenopus. Development. 2000;127(6):1173–83. 10683171

69. Burdine RD, Schier AF. Conserved and divergent mechanisms in left-right axis formation. Genes Dev. 2000;14(7):763–76. 10766733

70. Hamada H, Meno C, Watanabe D, Saijoh Y. Establishment of vertebrate left-right asymmetry. Nat Rev Genet. 2002;3(2):103–13. doi: 10.1038/nrg732 11836504

71. Nonaka S, Shiratori H, Saijoh Y, Hamada H. Determination of left-right patterning of the mouse embryo by artificial nodal flow. Nature. 2002;418(6893):96–9. doi: 10.1038/nature00849 12097914

72. Schier AF. Nodal signaling in vertebrate development. Annu Rev Cell Dev Biol. 2003;19:589–621. doi: 10.1146/annurev.cellbio.19.041603.094522 14570583

73. Peterson AJ, O’Connor MB. Strategies for exploring TGF-beta signaling in Drosophila. Methods. 2014;68(1):183–93. doi: 10.1016/j.ymeth.2014.03.016 24680699

74. Munz B, Smola H, Engelhardt F, Bleuel K, Brauchle M, Lein I, et al. Overexpression of activin A in the skin of transgenic mice reveals new activities of activin in epidermal morphogenesis, dermal fibrosis and wound repair. EMBO J. 1999;18(19):5205–15. doi: 10.1093/emboj/18.19.5205 10508154

75. Wankell M, Munz B, Hubner G, Hans W, Wolf E, Goppelt A, et al. Impaired wound healing in transgenic mice overexpressing the activin antagonist follistatin in the epidermis. EMBO J. 2001;20(19):5361–72. doi: 10.1093/emboj/20.19.5361 11574468

76. Bryant DM, Johnson K, DiTommaso T, Tickle T, Couger MB, Payzin-Dogru D, et al. A Tissue-Mapped Axolotl De Novo Transcriptome Enables Identification of Limb Regeneration Factors. Cell Rep. 2017;18(3):762–76. doi: 10.1016/j.celrep.2016.12.063 28099853

77. Weiss J, Harris PE, Halvorson LM, Crowley WF, Jr., Jameson JL. Dynamic regulation of follicle-stimulating hormone-beta messenger ribonucleic acid levels by activin and gonadotropin-releasing hormone in perifused rat pituitary cells. Endocrinology. 1992;131(3):1403–8. doi: 10.1210/endo.131.3.1505470 1505470

78. Vassalli A, Matzuk MM, Gardner HA, Lee KF, Jaenisch R. Activin/inhibin beta B subunit gene disruption leads to defects in eyelid development and female reproduction. Genes Dev. 1994;8(4):414–27. doi: 10.1101/gad.8.4.414 8125256

79. Xia Y, Schneyer AL. The biology of activin: recent advances in structure, regulation and function. J Endocrinol. 2009;202(1):1–12. doi: 10.1677/JOE-08-0549 19273500

80. Pearson BJ, Eisenhoffer GT, Gurley KA, Rink JC, Miller DE, Sánchez Alvarado A. Formaldehyde-based whole-mount in situ hybridization method for planarians. Dev Dyn. 2009;238(2):443–50. doi: 10.1002/dvdy.21849 19161223


Článek vyšel v časopise

PLOS Genetics


2021 Číslo 3
Nejčtenější tento týden
Nejčtenější v tomto čísle
Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

Důležitost adherence při depresivním onemocnění
nový kurz
Autoři: MUDr. Eliška Bartečková, Ph.D.

Koncepce osteologické péče pro gynekology a praktické lékaře
Autoři: MUDr. František Šenk

Sekvenční léčba schizofrenie
Autoři: MUDr. Jana Hořínková, Ph.D.

Hypertenze a hypercholesterolémie – synergický efekt léčby
Autoři: prof. MUDr. Hana Rosolová, DrSc.

Multidisciplinární zkušenosti u pacientů s diabetem
Autoři: Prof. MUDr. Martin Haluzík, DrSc., prof. MUDr. Vojtěch Melenovský, CSc., prof. MUDr. Vladimír Tesař, DrSc.

Všechny kurzy
Přihlášení
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se