β-catenin/Wnt signaling controls progenitor fate in the developing and regenerating zebrafish retina

Neural Development

Pamela A Raymond²  Annemarie Papandrea¹  Kavon Kaboli¹  Ariel Moses²  Lily Hu²  Jason R Meyers² 

[1] Department of Biology, Colgate University, Hamilton, NY, 13346, USA;Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, 48104, USA

关键词: Ciliary marginal zone;    Zebrafish;    Proliferation;    Regeneration;    Development;    Retina;    XAV939;    1-azakenpaullone;    β-catenin/Wnt;   

Others  :  807195
DOI  :  10.1186/1749-8104-7-30

 received in 2012-05-24, accepted in 2012-08-15,  发布年份 2012

【 摘 要 】

Background

The zebrafish retina maintains two populations of stem cells: first, the germinal zone or ciliary marginal zone (CMZ) contains multipotent retinal progenitors that add cells to the retinal periphery as the fish continue to grow; second, radial glia (Müller cells) occasionally divide asymmetrically to generate committed progenitors that differentiate into rod photoreceptors, which are added interstitially throughout the retina with growth. Retinal injury stimulates Müller glia to dedifferentiate, re-enter the cell cycle, and generate multipotent retinal progenitors similar to those in the CMZ to replace missing neurons. The specific signals that maintain these two distinct populations of endogenous retinal stem cells are not understood.

Results

We used genetic and pharmacological manipulation of the β-catenin/Wnt signaling pathway to show that it is required to maintain proliferation in the CMZ and that hyperstimulation of β-catenin/Wnt signaling inhibits normal retinal differentiation and expands the population of proliferative retinal progenitors. To test whether similar effects occur during regeneration, we developed a method for making rapid, selective photoreceptor ablations in larval zebrafish with intense light. We found that dephosphorylated β-catenin accumulates in Müller glia as they re-enter the cell cycle following injury, but not in Müller glia that remain quiescent. Activation of Wnt signaling is required for regenerative proliferation, and hyperstimulation results in loss of Müller glia from the INL as all proliferative cells move into the ONL.

Conclusions

β-catenin/Wnt signaling is thus required for the maintenance of retinal progenitors during both initial development and lesion-induced regeneration, and is sufficient to prevent differentiation of those progenitors and maintain them in a proliferative state. This suggests that the β-catenin/Wnt cascade is part of the shared molecular circuitry that maintains retinal stem cells for both homeostatic growth and epimorphic regeneration.

【 授权许可】

   
2012 Meyers et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Johns PR: Growth of the adult goldfish eye. III. Source of the new retinal cells. J Comp Neurol 1977, 176:343-357.
• [2]Raymond PA, Barthel LK, Bernardos RL, Perkowski JJ: Molecular characterization of retinal stem cells and their niches in adult zebrafish. BMC Dev Biol 2006, 6:36.
• [3]Hitchcock PF, Raymond PA: The teleost retina as a model for developmental and regeneration biology. Zebrafish 2004, 1:257-271.
• [4]Bernardos RL, Barthel LK, Meyers JR, Raymond PA: Late-stage neuronal progenitors in the retina are radial Müller glia that function as retinal stem cells. J Neurosci 2007, 27:7028-7040.
• [5]Thummel R, Kassen SC, Enright JM, Nelson CM, Montgomery JE, Hyde DR: Characterization of Müller glia and neuronal progenitors during adult zebrafish retinal regeneration. Exp Eye Res 2008, 87:433-444.
• [6]Brockerhoff SE, Fadool JM: Genetics of photoreceptor degeneration and regeneration in zebrafish. Cell Mol Life Sci 2011, 68:651-659.
• [7]Nusse R: Wnt signaling and stem cell control. Cell Res 2008, 18:523-527.
• [8]Wend P, Holland JD, Ziebold U, Birchmeier W: Wnt signaling in stem and cancer stem cells. Semin Cell Dev Biol 2010, 21:855-863.
• [9]Kubo F, Takeichi M, Nakagawa S: Wnt2b controls retinal cell differentiation at the ciliary marginal zone. Development 2003, 130:587-598.
• [10]Yamaguchi M, Tonou-Fujimori N, Komori A, Maeda R, Nojima Y, Li H, Okamoto H, Masai I: Histone deacetylase 1 regulates retinal neurogenesis in zebrafish by suppressing Wnt and Notch signaling pathways. Development 2005, 132:3027-3043.
• [11]Van Raay TJ, Moore KB, Iordanova I, Steele M, Jamrich M, Harris WA, Vetter ML: Frizzled 5 signaling governs the neural potential of progenitors in the developing Xenopus retina. Neuron 2005, 46:23-36.
• [12]Kubo F, Takeichi M, Nakagawa S: Wnt2b inhibits differentiation of retinal progenitor cells in the absence of Notch activity by downregulating the expression of proneural genes. Development 2005, 132:2759-2770.
• [13]Nadauld LD, Chidester S, Shelton DN, Rai K, Broadbent T, Sandoval IT, Peterson PW, Manos EJ, Ireland CM, Yost HJ, Jones DA: Dual roles for adenomatous polyposis coli in regulating retinoic acid biosynthesis and Wnt during ocular development. Proc Natl Acad Sci USA 2006, 103:13409-13414.
• [14]Stephens WZ, Senecal M, Nguyen M, Piotrowski T: Loss of adenomatous polyposis coli (apc) results in an expanded ciliary marginal zone in the zebrafish eye. Dev Dyn 2010, 239:2066-2077.
• [15]Denayer T, Locker M, Borday C, Deroo T, Janssens S, Hecht A, van Roy F, Perron M, Vleminckx K: Canonical Wnt signaling controls proliferation of retinal stem/progenitor cells in postembryonic Xenopus eyes. Stem Cells 2008, 26:2063-2074.
• [16]Agathocleous M, Iordanova I, Willardsen MI, Xue XY, Vetter ML, Harris WA, Moore KB: A directional Wnt/beta-catenin-Sox2-proneural pathway regulates the transition from proliferation to differentiation in the Xenopus retina. Development 2009, 136:3289-3299.
• [17]Osakada F, Ooto S, Akagi T, Mandai M, Akaike A, Takahashi M: Wnt signaling promotes regeneration in the retina of adult mammals. J Neurosci 2007, 27:4210-4219.
• [18]Del Debbio CB, Balasubramanian S, Parameswaran S, Chaudhuri A, Qiu F, Ahmad I: Notch and Wnt signaling mediated rod photoreceptor regeneration by Müller cells in adult mammalian retina. PLoS One 2010, 5:e12425.
• [19]Ramachandran R, Zhao X-F, Goldman D: Ascl1a/Dkk/{beta}-catenin signaling pathway is necessary and glycogen synthase kinase-3{beta} inhibition is sufficient for zebrafish retina regeneration. Proc Natl Acad Sci USA 2011, 108:15858-15863.
• [20]Heisenberg CP, Brand M, Jiang YJ, Warga RM, Beuchle D, van Eeden FJ, Furutani-Seiki M, Granato M, Haffter P, Hammerschmidt M, Kane DA, Kelsh RN, Mullins MC, Odenthal J, Nusslein-Volhard C: Genes involved in forebrain development in the zebrafish, Danio rerio. Development 1996, 123:191-203.
• [21]Heisenberg CP, Houart C, Take-Uchi M, Rauch GJ, Young N, Coutinho P, Masai I, Caneparo L, Concha ML, Geisler R, Dale TC, Wilson SW, Stemple DL: A mutation in the Gsk3-binding domain of zebrafish Masterblind/Axin1 leads to a fate transformation of telencephalon and eyes to diencephalon. Genes Dev 2001, 15:1427-1434.
• [22]van de Water S, van de Wetering M, Joore J, Esseling J, Bink R, Clevers H, Zivkovic D: Ectopic Wnt signal determines the eyeless phenotype of zebrafish masterblind mutant. Development 2001, 128:3877-3888.
• [23]Klein PS, Melton DA: A molecular mechanism for the effect of lithium on development. Proc Natl Acad Sci USA 1996, 93:8455-8459.
• [24]Ryves WJ, Harwood AJ: Lithium inhibits glycogen synthase kinase-3 by competition for magnesium. Biochem Biophys Res Commun 2001, 280:720-725.
• [25]Kunick C, Lauenroth K, Leost M, Meijer L, Lemcke T: 1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3 beta. Bioorg Med Chem Lett 2004, 14:413-416.
• [26]Bernardos RL, Raymond PA: GFAP transgenic zebrafish. Gene Expr Patterns 2006, 6:1007-1013.
• [27]Li Z, Hu M, Ochocinska MJ, Joseph NM, Easter SS: Modulation of cell proliferation in the embryonic retina of zebrafish (Danio rerio). Dev Dyn 2000, 219:391-401.
• [28]Lewis JL, Bonner J, Modrell M, Ragland JW, Moon RT, Dorsky RI, Raible DW: Reiterated Wnt signaling during zebrafish neural crest development. Development 2004, 131:1299-1308.
• [29]Veien ES, Rosenthal JS, Kruse-Bend RC, Chien C-B, Dorsky RI: Canonical Wnt signaling is required for the maintenance of dorsal retinal identity. Development 2008, 135:4101-4111.
• [30]Huang S-MA, Mishina YM, Liu S, Cheung A, Stegmeier F, Michaud GA, Charlat O, Wiellette E, Zhang Y, Wiessner S, Hild M, Shi X, Wilson CJ, Mickanin C, Myer V, Fazal A, Tomlinson R, Serluca F, Shao W, Cheng H, Shultz M, Rau C, Schirle M, Schlegl J, Ghidelli S, Fawell S, Lu C, Curtis D, Kirschner MW, Lengauer C, et al.: Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature 2009, 461:614-620.
• [31]Kassen SC, Thummel R, Burket CT, Campochiaro LA, Harding MJ, Hyde DR: The Tg(ccnb1:EGFP) transgenic zebrafish line labels proliferating cells during retinal development and regeneration. Mol Vis 2008, 14:951-963.
• [32]Staal FJT, Van Noort M, Strous GJ, Clevers HC: Wnt signals are transmitted through N-terminally dephosphorylated beta-catenin. EMBO Rep 2002, 3:63-68.
• [33]Barker N, van de Wetering M, Clevers H: The intestinal stem cell. Genes Dev 2008, 22:1856-1864.
• [34]Darken RS, Wilson PA: Axis induction by wnt signaling: target promoter responsiveness regulates competence. Dev Biol 2001, 234:42-54.
• [35]Stoick-Cooper CL, Weidinger G, Riehle KJ, Hubbert C, Major MB, Fausto N, Moon RT: Distinct Wnt signaling pathways have opposing roles in appendage regeneration. Development 2007, 134:479-489.
• [36]Lin G, Slack JMW: Requirement for Wnt and FGF signaling in Xenopus tadpole tail regeneration. Dev Biol 2008, 316:323-335.
• [37]Qin Z, Barthel LK, Raymond PA: Genetic evidence for shared mechanisms of epimorphic regeneration in zebrafish. Proc Natl Acad Sci USA 2009, 106:9310-9315.
• [38]Ogata K, Kurki P, Celis JE, Nakamura RM, Tan EM: Monoclonal antibodies to a nuclear protein (PCNA/cyclin) associated with DNA replication. Exp Cell Res 1987, 168:475-486.
• [39]Tetsu O, McCormick F: Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature 1999, 398:422-426.
• [40]Wang X, Kopinke D, Lin J, McPherson AD, Duncan RN, Otsuna H, Moro E, Hoshijima K, Grunwald DJ, Argenton F, Chien C-B, Murtaugh LC, Dorsky RI: Wnt signaling regulates post-embryonic hypothalamic progenitor differentiation. Developmental Cell
• [41]Kroehne V, Freudenreich D, Hans S, Kaslin J, Brand M: Regeneration of the adult zebrafish brain from neurogenic radial glia-type progenitors. Development 2011, 138:4831-4841.
• [42]Lee JE, Wu S-F, Goering LM, Dorsky RI: Canonical Wnt signaling through Lef1 is required for hypothalamic neurogenesis. Development 2006, 133:4451-4461.
• [43]Liu H, Mohamed O, Dufort D, Wallace VA: Characterization of Wnt signaling components and activation of the Wnt canonical pathway in the murine retina. Dev Dyn 2003, 227:323-334.
• [44]Tropepe V, Coles BL, Chiasson BJ, Horsford DJ, Elia AJ, McInnes RR, van der Kooy D: Retinal stem cells in the adult mammalian eye. Science 2000, 287:2032-2036.
• [45]Westerfield M: The Zebrafish Book. A Guide for the Laboratory Use of Zebrafish (Danio rerio). 4th edition. Eugene, OR: University of Oregon Press; 2007.
• [46]Barthel LK, Raymond PA: Improved method for obtaining 3-microns cryosections for immunocytochemistry. J Histochem Cytochem 1990, 38:1383-1388.
• [47]Mathers PH, Grinberg A, Mahon KA, Jamrich M: The Rx homeobox gene is essential for vertebrate eye development. Nature 1997, 387:603-607.
• [48]Passini MA, Kurtzman AL, Canger AK, Asch WS, Wray GA, Raymond PA, Schechter N: Cloning of zebrafish vsx1: expression of a paired-like homeobox gene during CNS development. Dev Genet 1998, 23:128-141.
• [49]Thisse B, Pflumio S, Fürthauer M, Loppin B, Heyer V, Degrave A, Woehl R, Lux A, Steffan T, Charbonnier XQ, Thisse C: Expression of the zebrafish genome during embryogenesis. ZFINhttp://zfin.org webcite