Abstract
Co-repressor Groucho/Transducin-Like Enhancer of split (TLE) interacts with transcription factors that are expressed in the central nervous system (CNS), and regulates transcriptional activities. In this study, we examined the contribution of Groucho/TLE to CNS development in Xenopus. The functional inhibition of Groucho/TLE using the WRPW motif as a competitor resulted in the conversion of the ventral cell into the dorsal fate in the prospective diencephalon. We also found that the neural plate was expanded laterally without inhibiting neural crest development. In tailbud, the disturbance of trigeminal ganglion development was observed. These observations allow us to conclude that Groucho/TLE plays important roles in the induction and patterning of distinct CNS territories. We found that Xtcf-3 is involved in some of the patterning in these territories. We generated the variant of Xtcf-3, Xtcf-3BDN-, which is suspected to interfere with the interaction between endogenous Groucho/TLE and Xtcf-3. The transcriptional activation of the Xtcf-3-target genes in response to endogenous Wnt/β-catenin signaling by the overexpression of Xtcf-3BDN- led to a reduction of the ventral diencephalon. This result indicates that transcriptional repression by the Groucho/TLE-Xtcf-3 complex is important for ventral diencephalon patterning. This idea is supported by the finding that the overexpression of the dominant-negative form of Xtcf-3 or axil causes the expansion of the ventral diencephalon. Based on these data, we propose that the localized activation of Wnt/β-catenin signaling, which converts Tcf from a repressor to an activator, is required for the establishment of dorsal-ventral patterning in the prospective diencephalon.
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References
Baker JC, Beddington RS, Harland RM (1999) Wnt signaling in Xenopus embryos inhibits Bmp4 expression and activates neural development. Genes Dev 13:3149–3159
Bang AG, Papalopulu N, Goulding MD, Kintner C (1999) Expression of Pax-3 in the lateral neural plate is dependent on a Wnt-mediated signal from posterior nonaxial mesoderm. Dev Biol 212:366–380
Barbieri AM, Lupo G, Bulfone A, Andreazzoli M, Mariani M, Fougerousse F, Consalez GG, Borsani G, Beckmann JS, Barsacchi G, Ballabio A, Banfi S (1999) A homeobox gene, vax2, controls the patterning of the eye dorsoventral axis. Proc Natl Acad Sci USA 96:10729–10734
Behrens J, von Kries JP, Kühl M, Bruhn L, Wedlich D, Grosschedl R (1996) Functional interaction of β-catenin with the transcription factor LEF-1. Nature 382:742–746
Blitz IL, Cho KWY (1995) Anterior neurectoderm is progressively induced during gastrulation: the role of the Xenopus homeobox gene orthodenticle. Development 121:993–1004
Bourguignon C, Li J, Papalopulu N (1998) XBF-1, a winged helix transcription factor with dual activity, has a role in positioning neurogenesis in Xenopus competent ectoderm. Development 125:4889–4900
Bouwmeester T, Kim S, Sasai Y, Lu B, De Robertis EM (1996) Cerberus is a head-inducing secreted factor expressed in the anterior endoderm of Spemann’s organizer. Nature 382:595–601
Bradley LC, Snape A, Bhatt S, Wilkinson DG (1993) The structure and expression of the Xenopus Krox-20 gene: conserved and divergent patterns of expression in rhombomeres and neural crest. Mech Dev 40:73–84
Bradley L, Sun B, Collins-Racie L, LaVallie E, McCoy J, Sive H (2000) Different activities of the frizzled-related proteins frzb2 and sizzled2 during Xenopus anteroposterior patterning. Dev Biol 227:118–132
Camus A, Davidson BP, Billiards S, Khoo P, Rivera-Pérez JA, Wakamiya M, Behringer RR, Tam PP (2000) The morphogenetic role of midline mesendoderm and ectoderm in the development of the forebrain and the midbrain of the mouse embryo. Development 127:1799–1813
Casarosa S, Andreazzoli M, Simeone A, Barsacchi G (1997) Xrx1, a novel Xenopus homeobox gene expression during eye and pineal gland development. Mech Dev 61:187–198
Cavallo RA, Cox RT, Moline MM, Roose J, Polevoy GA, Clevers H, Peifer M, Bejsovec A (1998) Drosophila Tcf and Groucho interact to repress Wingless signaling activity. Nature 395:604–608
Chang C, Hemmati-Brivanlou A (1998) Neural crest induction by Xwnt7B in Xenopus. Dev Biol 194:129–134
Chitnis A, Henrique D, Lewis J, Ish-Horowicz D, Kintner C (1995) Primary neurogenesis in Xenopus embryos regulated by a homologue of the Drosophila neurogenic gene Delta. Nature 375:761–766
Choi CY, Lee YM, Kim YH, Park T, Jeon BH, Schulz RA, Kim Y (1999) The homeodomain transcription factor NK-4 acts as either a transcriptional activator or repressor and interacts with the p300 coactivator and the Groucho corepressor. J Biol Chem 274:31543–31552
Choudhury BK, Kim J, Kung HF, Li SS (1997) Cloning and developmental expression of Xenopus cDNAs encoding the Enhancer of split groucho and related proteins. Gene 195:41–48
Cox WG, Hemmati-Brivanlou A (1995) Caudalization of neural fate by tissue recombination and bFGF. Development 121:4349–4358
Dorsky RI, Itoh M, Moon RT, Chitnis A (2003) Two tcf3 genes cooperate to pattern the zebrafish brain. Development 130:1937–1947
Eagleson GW, Dempewolf RD (2002) The role of the anterior neural ridge and Fgf-8 in early forebrain patterning and regionalization in Xenopus laevis. Comp Biochem Physiol B Biochem Mol Biol 132:179–189
Eberhard D, Jiménez G, Heavey B, Busslínger M (2000) Transcriptional repression by Pax5 (BSAP) through interaction with corepressors of the Groucho family. EMBO J 19:2292–2303
Echelard Y, Epstein DJ, St-Jacques B, Shen L, Mohler J, McMahon JA, McMahon AP (1993) Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity. Cell 75:1417–1430
Ericson J, Muhr J, Placzek M, Lints T, Jessell TM, Edlund T (1995) Sonic hedgehog induces the differentiation of ventral forebrain neurons: a common signal for ventral patterning within the neural tube. Cell 81:747–756
Fisher AL, Caudy M (1998) Groucho proteins: transcriptional corepressors for specific subsets of DNA-binding transcription factors in vertebrates and invertebrates. Genes Dev 12:1931–1940
Fisher A, Ohsako S, Caudy M (1996) The WRPW motif of the Hairy-related basic helix-loop-helix repressor proteins acts as a 4-amino-acid transcription repression and protein-protein interaction domain. Mol Cell Biol 16:2670–2677
Fredieu JR, Cui Y, Maier D, Danilchik MV, Christian JL (1997) Xwnt-8 and lithium can act upon either dorsal mesodermal or neurectodermal cells to cause a loss of forebrain in Xenopus embryos. Dev Biol 186:100–114
Furuta Y, Piston DW, Hogan BL (1997) Bone morphogenetic proteins (BMPs) as regulators of dorsal forebrain development. Development 124:2203–2212
Gamse J, Sive H (2000) Vertebrate anteroposterior patterning: the Xenopus neuroectoderm as a paradigm. BioEssays 22:976–986
Glinka A, Wu W, Delius H, Monaghan AP, Blumenstock C, Niehrs C (1998) Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction. Nature 391:357–362
Hallonet M, Kaestner KH, Martin-Parras L, Sasaki H, Betz UA, Ang SL (2002) Maintenance of the specification of the anterior definitive endoderm and forebrain depends on the axial mesendoderm: a study using HNF3β/Foxa2 conditional mutants. Dev Biol 243:20–33
Harland RM (1991) In situ hybridization: an improved whole-mount method for Xenopus embryos. Methods Cell Biol 36:685–695
Hartley DA, Preiss A, Artavanis-Tsakonas S (1988) A deduced gene product from the Drosophila neurogenic locus, enhancer of split, shows homology to mammalian G-protein β subunit. Cell 55:785–795
Hawley SH, Wunnenberg-Stapleton K, Hashimoto C, Laurent MN, Watabe T, Blumberg BW, Cho KW (1995) Disruption of BMP signals in embryonic Xenopus ectoderm leads to direct neural induction. Genes Dev 9:2923–2935
Hemmati-Brivanlou A, de la Torre JR, Holt C, Harland RM (1991) Cephalic expression and molecular characterization of Xenopus En-2. Development 111:715–724
Hirsch N, Harris WA (1997) Xenopus Pax-6 and retinal development. J Neurobiology 32:45–61
Huber O, Korn R, McLaughlin J, Ohsugi M, Herrmann BG, Kemler R (1996) Nuclear localization of β-catenin by interaction with transcription factor LEF-1. Mech Dev 59:3–10
Ikeya M, Lee SM, Johnson JE, McMahon AP, Takada S (1997) Wnt signaling required for expansion of neural crest and CNS progenitors. Nature 389:966–970
Jiménez G, Paroush Z, Ish-Horowicz D (1997) Groucho acts as a corepressor for a subset of negative regulators, including Hairy and Engrailed. Genes Dev 11:3072–3082
Jonas E, Sargent TD, Dawid IB (1985) Epidermal keratin gene expressed in embryos of Xenopus laevis. Proc Natl Acad Sci USA 82:5413–5417
Kiecker C, Niehrs C (2001) A morphogen gradient of Wnt/β-catenin signaling regulates anteroposterior neural patterning in Xenopus. Development 128:4189–4201
Kishi M, Mizuseki K, Sasai N, Yamazaki H, Shiota K, Nakanishi S, Sasai Y (2000) Requirement of Sox2-mediated signaling for differentiation of early Xenopus neuroectoderm. Development 127:791–800
Knecht AK, Harland RM (1997) Mechanisms of dorsal-ventral patterning in noggin-induced neural tissue. Development 124:2477–2488
Knecht AK, Good PJ, Dawid IB, Harland RM (1995) Dorsal-ventral patterning and differentiation of noggin-induced neural tissue in the absence of mesoderm. Development 121:1927–1935
Kobayashi M, Nishikawa K, Suzuki T, Yamamoto M (2001) The homeobox protein Six3 interacts with the Groucho corepressor and acts as a transcriptional repressor in eye and forebrain formation. Dev Biol 232:315–326
Kolm PJ, Sive HL (1995) Regulation of the Xenopus labial homeodomain genes, HoxA1 and HoxD1: activation by retinoids and peptide growth factors. Dev Biol 167:34–49
Lagutin OV, Zhu CC, Kobayashi D, Topczewski J, Shimamura K, Puelles L, Russell HRC, Mckinnon PJ, Solnica-Krezel L, Oliver G (2003) Six3 repression of Wnt signaling in the anterior neuroectoderm is essential for vertebrate forebrain development. Genes Dev 17:368–379
Laurent MN, Blitz IL, Hashimoto C, Rothbacher U, Cho KW (1997) The Xenopus homeobox gene twin mediates Wnt induction of goosecoid in establishment of Spemann’s organizer. Development 124:4905–4916
Lee SM, Tole S, Grove E, McMahon AP (2000) A local Wnt-3a signal is required for development of the mammalian hippocampus. Development 127:457–467
Leyns L, Bouwmeester T, Kim SH, Piccolo S, De Robertis EM (1997) Frzb-1 is a secreted antagonist of Wnt signaling expressed in the Spemann organizer. Cell 88:747–756
Liem KF Jr, Tremml G, Roelink H, Jessell TM (1995) Dorsal differentiation of neural plate cells induced by BMP-mediated signals from epidermal ectoderm. Cell 82:969–979
Lumsden A, Krumlauf R (1996) Patterning the vertebrate neuraxis. Science 274:1109–1115
Lupo G, Harris WA, Barsacchi G, Vignali R (2002) Induction and patterning of the telencephalon in Xenopus laevis. Development 129:5421–5436
Ma Q, Kintner C, Anderson DJ (1996) Identification of neurogenin, a vertebrate neuronal determination gene. Cell 87:43–52
Mayor R, Morgan R, Sargent MG (1995) Induction of the prospective neural crest of Xenopus. Development 121:767–777
McGrew LL, Lai CJ, Moon RT (1995) Specification of the anteroposterior neural axis through synergistic interaction of the Wnt signaling cascade with noggin and follistatin. Dev Biol 172:337–342
McGrew LL, Hoppler S, Moon RT (1997) Wnt and FGF pathways cooperatively pattern anteroposterior neural ectoderm in Xenopus. Mech Dev 69:105–114
Michiue T, Fukui A, Yukita A, Sakurai K, Danno H, Kikuchi A, Asashima M (2004) XIdax, an inhibitor of the canonical Wnt pathway, is required for anterior neural structure formation in Xenopus. Dev Dyn 230:79–90
Mizuseki K, Kishi M, Matsui M, Nikanishi S, Sasai Y (1998) Xenopus Zic-related-1 and Sox-2, two factors induced by chordin, have distinct activities in the initiation of neural induction. Development 125:579–587
Molenaar M, van de Wetering M, Oosterwegel M, Peterson-Maduro J, Godsave S, Korinek V, Roose J, Destrée O, Clevers H (1996) Xtcf-3 transcription factor mediates β-catenin-induced axis formation in Xenopus embryos. Cell 86:391–399
Molenaar M, Roose J, Peterson J, Venanzi S, Clevers H, Destree O (1998) Differential expression of the HMG box transcription factors Xtcf-3 and XLef-1 during early Xenopus development. Mech Dev 75:151–154
Molenaar M, Brian E, Roose J, Clevers H, Destrée O (2000) Differential expression of the Groucho-related genes 4 and 5 during early development of Xenopus laevis. Mech Dev 91:311–315
Muroyama Y, Fujihara M, Ikeya M, Kondoh H, Takada S (2002) Wnt signaling plays an essential role in neuronal specification of the dorsal spinal cord. Genes Dev 16:548–553
Niehrs C (1999) Head in the WNT: the molecular nature of Spemann’s head organizer. Trends Genet 15:314–319
Nieuwkoop PD, Faber J (1956) Normal table of Xenopus laevis (Daudin). Biomedical Press, Amsterdam
Nordstrom U, Jessell TM, Edlund T (2002) Progressive induction of caudal neural character by graded Wnt signaling. Nat Neurosci 5:525–532
Ogino H, Yasuda K (2000) Sequential activation of transcriptional factors in lens induction. Dev Growth Differ 42:437–448
Pannese M, Polo C, Andreazzoli M, Vignali R, Kablar B, Barsacchi G, Boncinelli E (1995) The Xenopus homologue of Otx2 is a maternal homeobox gene that demarcates and specifies anterior body regions. Development 121:707–720
Papalopulu N, Kintner C (1996) A posteriorising factor, retinoic acid, reveals that anteroposterior patterning controls the timing of neuronal differentiation in Xenopus neuroectoderm. Development 122:3409–3418
Paroush Z, Finley RL Jr, Kidd T, Wainwright SM, Ingham PW, Brent R, Ish-Horowicz D (1994) Groucho is required for Drosophila neurogenesis, segmentation, and sex determination and interacts directly with Hairy-related bHLH proteins. Cell 79:805–815
Pera EM, De Robertis EM (2000) A direct screen for secreted proteins in Xenopus embryos identifies distinct activities for the Wnt antagonists Crescent and Frzb-1. Mech Dev 96:183–195
Perry WL III, Vasicek TJ, Lee JJ, Rossi JM, Zeng L, Zhang T, Tilghman SM, Costantini F (1995) Phenotypic and molecular analysis of a transgenic insertional allele of the mouse Fused locus. Genetics 141:321–332
Pinson KI, Brennan J, Monkley S, Avery BJ, Skarnes WC (2000) An LDL-receptor-related protein mediates Wnt signaling in mice. Nature 407:535–538
Roose J, Molenaar M, Peterson J, Hurenkamp J, Brantjes H, Moerer P, van de Wetering M, Destree O, Clevers H (1998) The Xenopus Wnt effector XTcf-3 interacts with Groucho-related transcriptional repressors. Nature 395:608–612
Saint-Jeannet JP, He X, Varmus HE, Dawid IB (1997) Regulation of dorsal fate in the neuraxis by Wnt-1 and Wnt-3a. Proc Natl Acad Sci USA 94:13713–13718
Sasai N, Mizuseki K, Sasai Y (2001) Requirement of FoxD3-class signaling for neural crest determination in Xenopus. Development 128:2525–2536
Shimamura K, Rubenstein JLR (1997) Inductive interactions direct early regionalization of the mouse forebrain. Development 124:2709–2718
Small EM, Vokes SA, Garriock RJ, Li D, Krieg PA (2000) Developmental expression of the Xenopus Nkx2-1 and Nkx2-4 genes. Mech Dev 96:259–262
Smith ST, Jaynes JB (1996) A conserved region of Engrailed, shared among all en-, gsc-, Nk1-, Nk2- and msh-class homeoproteins, mediates active transcriptional repression in vivo. Development 122:3141–3150
Takada S, Stark KL, Shea MJ, Vassileva G, McMahon JA, McMahon AP (1994) Wnt-3a regulates somite and tailbud formation in the mouse embryo. Genes Dev 8:174–189
Tsuji S, Cho KWY, Hashimoto C (2003) Expression pattern of a basic helix-loop-helix transcription factor Xhairy2b during Xenopus laevis development. Dev Genes Evol 213:407–411
Yamaguchi TP (2001) Heads or tails: wnts and anterior-posterior patterning. Curr Biol 11:R713–R724
Yao J, Lai E, Stifani S (2001) The winged-helix protein brain factor 1 interacts with Groucho and Hes proteins to repress transcription. Mol Cell Biol 21:1962–1972
Zhu CC, Dyer MA, Uchikawa M, Kondoh H, Lagutin OV, Oliver G (2002) Six3-mediated auto repression and eye development requires its interaction with members of the Groucho-related family of co-repressors. Development 129:2835–2849
Zimmerman K, Shih J, Bars J, Collazo A, Anderson DJ (1993) XASH-3, a novel Xenopus achaete-scute homolog, provides an early marker of planar neural induction and position along the mediolateral axis of the neural plate. Development 119:221–232
Zuber ME, Perron M, Philpott A, Bang A, Harris WA (1999) Giant eyes in Xenopus laevis by overexpression of XOptx2. Cell 98:341–352
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We thank all Hashimoto lab members especially M. Yamaguchi for helpful comments and critical reading of this manuscript.
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Tsuji, S., Hashimoto, C. Choice of either β-catenin or Groucho/TLE as a co-factor for Xtcf-3 determines dorsal-ventral cell fate of diencephalon during Xenopus development. Dev Genes Evol 215, 275–284 (2005). https://doi.org/10.1007/s00427-005-0474-0
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DOI: https://doi.org/10.1007/s00427-005-0474-0