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1095-564X36712012Jul01Developmental biologyDev BiolMutual repression between Gbx2 and Otx2 in sensory placodes reveals a general mechanism for ectodermal patterning.556555-6510.1016/j.ydbio.2012.04.025In the vertebrate head, central and peripheral components of the sensory nervous system have different embryonic origins, the neural plate and sensory placodes. This raises the question of how they develop in register to form functional sense organs and sensory circuits. Here we show that mutual repression between the homeobox transcription factors Gbx2 and Otx2 patterns the placode territory by influencing regional identity and by segregating inner ear and trigeminal progenitors. Activation of Otx2 targets is necessary for anterior olfactory, lens and trigeminal character, while Gbx2 function is required for the formation of the posterior otic placode. Thus, like in the neural plate antagonistic interaction between Otx2 and Gbx2 establishes positional information thus providing a general mechanism for rostro-caudal patterning of the ectoderm. Our findings support the idea that the Otx/Gbx boundary has an ancient evolutionary origin to which different modules were recruited to specify cells of different fates.Copyright © 2012 Elsevier Inc. All rights reserved.SteventonBenBDepartment of Craniofacial Development, King's College London, Guy's Campus, Tower Wing Floor 27, London SE1 9RT, UK.MayorRobertoRStreitAndreaAeng084247WT_Wellcome TrustUnited KingdomG0801145MRC_Medical Research CouncilUnited KingdomMR/J000655/1MRC_Medical Research CouncilUnited KingdomJournal ArticleResearch Support, Non-U.S. Gov't20120428
United StatesDev Biol03727620012-16060Gbx2 protein, Xenopus0Homeodomain Proteins0Otx Transcription Factors0Otx2 protein, Xenopus0Xenopus ProteinsIMAnimalsChick EmbryoEctodermembryologyHomeodomain ProteinsmetabolismMorphogenesisOtx Transcription FactorsSense OrgansembryologyXenopusembryologyXenopus Proteinsmetabolism2012312201241320124172012596020125960201273160201271ppublish22564795PMC338400110.1016/j.ydbio.2012.04.025S0012-1606(12)00214-XAcampora D., Mazan S., Lallemand Y., Avantaggiato V., Maury M., Simeone A., Brulet P. Forebrain and midbrain regions are deleted in Otx2 −/− mutants due to a defective anterior neuroectoderm specification during gastrulation. Development. 1995;121:3279–3290.7588062Acampora D., Avantaggiato V., Tuorto F., Briata P., Corte G., Simeone A. Visceral endoderm-restricted translation of Otx1 mediates recovery of Otx2 requirements for specification of anterior neural plate and normal gastrulation. Development. 1998;125:5091–5104.9811592Acampora D., Avantaggiato V., Tuorto F., Simeone A. Genetic control of brain morphogenesis through Otx gene dosage requirement. Development. 1997;124:3639–3650.9342056Arendt D., Technau U., Wittbrodt J. Evolution of the bilaterian larval foregut. Nature. 2001;409:81–85.11343117Anderson A.M., Weasner B.M., Weasner B.P., Kumar J.P. Dual transcriptional activities of SIX proteins define their roles in normal and ectopic eye development. Development. 2012;139:991–1000.PMC327436022318629Aybar M.J., Nieto M.A., Mayor R. Snail precedes slug in the genetic cascade required for the specification and migration of the Xenopus neural crest. Development. 2003;130:483–494.12490555Bailey A.P., Bhattacharyya S., Bronner-Fraser M., Streit A. Lens specification is the ground state of all sensory placodes, from which FGF promotes olfactory identity. Dev. Cell. 2006;11:505–517.17011490Baker C.V., Stark M.R., Marcelle C., Bronner-Fraser M. Competence, specification and induction of Pax-3 in the trigeminal placode. Development. 1999;126:147–156.9834194Baker C.V., Bronner-Fraser M. Establishing neuronal identity in vertebrate neurogenic placodes. Development. 2000;127:3045–3056.10862742Baker C.V.H., Bronner-Fraser M. Vertebrate Cranial Placodes I. Embryonic Induction. Dev. Biol. 2001;232:1–61.11254347Bally-Cuif L., Gulisano M., Broccoli V., Bonicelli E. C-otx2 is expressed in two different phases of gastrulation and is sensitive to retinoic acid treatment in chick embryo. Mech. Dev. 1995;49:49–63.7748789Bang A.G., Papalopulu N., Kintner C., Goulding M.D. Expression of Pax-3 is initiated in the early neural plate by posteriorizing signals produced by the organizer and by posterior non-axial mesoderm. Development. 1997;124:2075–2085.9169853Bang A.G., Papalopulu N., Goulding M.D., Kintner C. Expression of Pax-3 in the lateral neural plate is dependent on a Wnt-mediated signal from posterior nonaxial mesoderm. Dev. Biol. 1999;212:366–380.10433827Benito-Gutiérrez È. A gene catalogue of the amphioxus nervous system. Int. J. Biol. Sci. 2006;2:149–160.PMC147415016763675Basch M., Bronner-Fraser M., García-Castro M. Specification of the neural crest occurs during gastrulation and requires Pax7. Nature. 2006;41:218–222.16688176Bastidas F., De Calisto J., Mayor R. Identification of neural crest competence territory: role of Wnt signaling. Dev. Dyn. 2004;229:109–117.14699582Bhattacharyya S., Bailey A.P., Bronner-Fraser M., Streit A. Segregation of lens and olfactory precursors from a common territory: cell sorting and reciprocity of Dlx5 and Pax6 expression. Dev. Biol. 2004;271:403–414.15223343Bhattacharyya S., Bronner-Fraser M. Competence, specification and commitment to an olfactory placode fate. Development. 2008;135:4165–4177.19029046Blitz I.L., Cho K.W. Anterior neurectoderm is progressively induced during gastrulation: the role of the Xenopus homeobox gene orthodenticle. Development. 1995;121:993–1004.7743941Broccoli V., Boncinelli E., Wurst W. The caudal limit of Otx2 expression positions the isthmic organizer. Nature. 1999;401:164–168.10490025Brugmann S.A., Pandur P.D., Kenyon K.L., Pignoni F., Moody S.A. Six1 promotes a placodal fate within the lateral neurogenic ectoderm by functioning as both a transcriptional activator and repressor. Development. 2004;131:5871–5881.15525662Castro L.F.C., Rasmussen S.L.K., Holland P.W.H., Holland N.D., Holland L.Z. A Gbx homeobox gene in amphioxus: Insights into ancestry of the ANTP class and evolution of the midbrain/hindbrain boundary. Dev.Biol. 2006;295:40–51.16687133Chang C., Hemmati-Brivanlou A. Neural crest induction by Xwnt7B in Xenopus. Dev. Biol. 1998;194:129–134.9473337David R., Ahrens K., Wedlich D., Schlosser G. Xenopus Eya1 demarcates all neurogenic placodes as well as migrating hypaxial muscle precursors. Mech. Dev. 2001;103:189–192.11335132Gallagher B.C., Henry J.J., Grainger R.M. Inductive processes leading to inner ear formation during Xenopus development. Dev. Biol. 1996;175:95–107.8608872García-Castro, Marcelle C., Bronner-Fraser M. Ectodermal Wnt functions as a neural crest inducer. Science. 2002;297:848–851.12161657Glavic A., Gómez-Skarmeta J.L., Mayor R. The homeoprotein Xiro1 is required for midbrain-hindbrain boundary formation. Development. 2002;129:1609–1621.11923198Gomez-Skarmeta J.L., Glavic A., de la Calle-Mustienes E., Modolell J., Mayor R. Xiro, a Xenopus homolog of Drosophila Iroquois complex genes, controls development at the neural plate. EMBO J. 1998;17:181–190.PMC11703699427752Grainger R.M., Mannion J.E., Cook T.L., Zygar C.A. Defining intermediate stages in cell determination: acquisition of a lens-forming bias in head ectoderm during lens determination. Dev. Genet. 1997;20:246–257.9216064Groves A.K., Bronner-Fraser M. Competence, specification and commitment in otic placode induction. Development. 2000;127:3489–3499.10903174Hamburger V., Hamilton H.L. A series of normal stages in the development of the chick embryo. J. Morph. 1951;88:49–92.24539719Harland R.M., Weintraub H. Translation of mRNA injected into Xenopus oocytes is specifically inhibited by antisense RNA. Cell Biol. 1985;10:1511–1514.PMC21137352411734Harland R.M. In situ hybridization: An improved whole-mount method for Xenopus embryos. Methods Cell Biol. 1991;36:685–695.1811161Heisenberg C.-P., Houart C., Take-uchi M., Rauch G., Young N., Coutinho P., Masai I., Caneparo L., Concha M.L., Geisler R. A mutation in the Gsk3β-binding domain of zebrafish masterblind/axin1 leads to a fate transformation of telencephalon and eyes to diencephalon. Genes. Dev. 2001;15:1427–1434.PMC31270511390362Heller N., Brändli A.W. Xenopus Pax-2/5/8 orthologues: Novel insights into Pax gene evolution and identification of Pax-8 as the earliest marker for otic and pronephric cell lineages. Dev. Genet. 1999;24:208–219.10322629Henry J.J., Grainger R.M. Inductive interactions in the spatial and temporal restriction of lens-forming potential in embryonic ectoderm of Xenopus laevis. Dev. Biol. 1987;124:200–214.3666306Hirth F., Kammermeier L., Frei E., Walldorf U., Noll M., Reichert H. An urbilaterian origin of the tripartite brain: developmental genetici nsights from Drosophila. Development. 2003;130 2365-237.12702651Hirsch N., Harris W.A. Xenopus Pax-6 and retinal development. J. Neurobiol. 1997;32:45–61.8989662Holland L.Z., Kene M., Williams N.A., Holland N.D. Sequence and embryonic expression of the amphioxus engrailed gene (AmphiEn): the metameric pattern of transcription resembles that of its segment-polarity homolog in Drosophila. Development. 1997;124:1723–1732.9165120Holland L.Z., Holland N.D., Schubert M. Developmental expression of AmphiWnt1, an amphioxus gene in the Wnt1/wingless subfamily. Dev. Genes. Evol. 2000;210:522–524.11180802Holland L.Z., Short S. Gene duplication, co-option and recruitment during the origin of the vertebrate brain from the invertebrate chordate brain. Brain Behav. Evol. 2008;72:91–105.18836256Holland L.Z. Chordate roots of the vertebrate nervous system: expanding the molecular toolkit. Nat. Rev. Neurosci. 2009;10:736–746.19738625Huang X., Hong C.-S., O'Donnell M., Saint-Jeannet J.-P. The doublesex-related gene, XDmrt4, is required for neurogenesis in the olfactory system. Proc. Nat. Acad. Sci. U.S.A. 2005;102:11349–11354.PMC118359416061812Katahira T., Sato T., Sugiyama S., Okafuji T., Araki I., Funahashi J.-I., Nakamura H. Interaction between Otx2 and Gbx2 defines the organizing center for the optic tectum. Mech. Dev. 2000;91:43–52.10704829Kenyon K.L., Moody S.A., Jamrich M. A novel fork head gene mediates early steps during Xenopus lens formation. Development. 1999;126:5107–5116.10529427Kim C.-H., Oda T., Itoh M., Jiang D., Artinger K.B., Chandrasekharappa S.C., Driever W., Chitnis A.B. Repressor activity of Headless/Tcf3 is essential for vertebrate head formation. Nature. 2000;407:913–916.PMC401883311057671Kobayashi M., Osanai H., Kawakami K., Yamamoto M. Expression of three zebrafish Six4 genes in the cranial sensory placodes and the developing somites. Mech. Dev. 2000;98:151–155.11044620Kozlowski D.J., Murakami T., Ho R.K., Weinberg E.S. Regional cell movement and tissue patterning in the zebrafish embryo revealed by fate mapping with caged fluorescein. Biochem. Cell Biol. 1997;75:551–562.9551179Ladher R.K., O'Neill P., Begbie J. From shared lineage to distinct functions: the development of the inner ear and epibranchial placodes. Development. 2010;137:1777–1785.20460364Li J.Y.H., Joyner A.L. Otx2 and Gbx2 are required for refinement and not induction of mid-hindbrain gene expression. Development. 2001;128:4979–4991.11748135Li J.Y.H., Lao Z., Joyner A.L. New regulatory interactions and cellular responses in the isthmic organizer region revealed by altering Gbx2 expression. Development. 2005;132:1971–1981.15790971Li B., Kuriyama S., Moreno M., Mayor R. The posteriorizing gene Gbx2 is a direct target of Wnt signalling and the earliest factor in neural crest induction. Development. 2009;136:3267–3278.PMC280829519736322Lin Z., Cantos R., Patente M., Wu D.K. Gbx2 is required for the morphogenesis of the mouse inner ear: a downstream candidate of hindbrain signaling. Development. 2005;132:2309–2318.15829521McCabe K.L., Bronner-Fraser M. Molecular and tissue interactions governing induction of cranial ectodermal placodes. Dev. Biol. 2009;332:189–195.PMC274748819500565McLarren K.W., Litsiou A., Streit A. DLX5 positions the neural crest and pre-placodal region at the border of the neural plate. Dev. Biol. 2003;259:34–47.12812786Meulemans D., Bronner-Fraser M. Insights from Amphioxus into the evolution of vertebrate cartilage. PLoS ONE. 2007;2:e787.PMC195007717726517Millet S., Campbell K., Epstein D.J., Losos K., Harris E., Joyner A.L. A role for Gbx2 in repression of Otx2 and positioning the mid/hindbrain organizer. Nature. 1999;401:161–164.10490024Nakamura H., Watanabe Y. Isthmus organizer and regionalization of the mesencephalon and metencephalon. Int. J. Dev. Biol. 2005;49:231–235.15906236New D.A.T. A new technique for the cultivation of the chick embryo in vitro. J. Embryol. Exp. Morphol. 1955;3:326–331.Nieuwkoop P.D., Faber J. 2nd edn. Daudin; North Holland, Amsterdam: 1967. Normal table of Xenopus laevis.Northcutt R.G., Gans C. The genesis of neural crest and epidermal placodes: are interpretation of vertebrate origins. Science. 1983;158:1–28.6346380Ogino H., Fisher M., Grainger R.M. Convergence of a head-field selector Otx2 and Notch signaling: a mechanism for lens specification. Development. 2008;135:249–258.PMC391816418057103Park B.-Y., Saint-Jeannet J.-P. Expression analysis of Runx3 and other Runx family members during Xenopus development. Gene Expression Pattern. 2010;10:159–166.PMC289603320433948Patthey C.D., Gunhaga L., Edlund T. Early development of the central and peripheral nervous system is coordinated byWnt and BMP signals. PLoS ONE. 2008;3:e1625.PMC222983818286182Pieper M., Eagleson G.W., Wosniok W., Schlosser G. Origin and segregation of cranial placodes in Xenopus laevis. Dev. Biol. 2011;360:257–275.21989028Raible F., Brand M. Divide et impera - the midbrain-hindbrain boundary and its organizer. Trends Neurosci. 2004;27:727–734.15541513Rhinn M., Dierich A., Shawlot W., Behringer R.R., Le Meur M., Ang S.L. Sequential roles for Otx2 in visceral endoderm and neuroectoderm for forebrain and midbrain induction and specification. Development. 1998;125:845–856.9449667Sato S., Ikeda K., Shioi G., Ochi H., Ogino H., Yajima H., Kawakami K. Conserved expression of mouse Six1 in the pre-placodal region (PPR) and identification of an enhancer for the rostral PPR. Dev. Biol. 2010;344:158–171.20471971Schlosser G. Induction and specification of cranial placodes. Dev. Biol. 2006;294:303–351.16677629Schlosser G. Making Senses: Development of vertebrate cranial placodes. Int. Rev. Cell Mol. Biol. 2010;283:129–234.20801420Shamim H., Mason I. Expression of Gbx-2 during early development of the chick embryo. Mech. Dev. 1998;76:157–159.9767156Simeone A., Acampora D., Gulisano M., Stornaiuolo A., Boncinelli E. Nested expression domains of four homeobox genes in developing rostral brain. Nature. 1992;358:687–690.1353865Simeone A., Acampora D., Mallamaci A., Stornaiuolo A., D'Apice M.R., Nigro V., Boncinelli E. A vertebrate gene related to orthodenticle contains a homeodomain of the bicoid class and demarcates anterior neuroectoderm in the gastrulating mouse embryo. EMBO J. 1993;12:2735–2747.PMC4135248101484Steinmetz P.R.H., Zelada-Gonzales F., Burgtorf C., Wittbrodt J., Arendt D. Polychaete trunk neuroectoderm converges and extends by mediolateral cell intercalation. Proc. Nat. Acad. Sci. 2007;104:2727–2732.PMC181524917301244Steinmetz P.R.H., Kostyuchenko R.P., Fischer A., Arendt D. The segmental pattern of Otx, Gbx, and Hox genes in the annelid Platynereis dumerilii. Evol. Dev. 2011;13:72–79.21210944Stern C.D., Ireland. G.W. An integrated experimental study of endoderm formation in avian embryos. Anat. Embryol. 1981;163:245–263.7340555Steventon B., Araya C., Linker C., Kuriyama S., Mayor R. Differential requirements of BMP and Wnt signalling during gastrulation and neurulation define two steps in neural crest induction. Development. 2009;136:771–779.PMC268594419176585Streit A. Extensive cell movements accompany formation of the otic placode. Dev. Biol. 2002;249:237–254.12221004Streit A. The preplacodal region: an ectodermal domain with multipotential progenitors that contribute to sense organs and cranial sensory ganglia. Int. J. Dev. Biol. 2007;51:447–461.17891708Streit A., Sockanathan S., Perez L., Rex M., Scotting P.J., Sharpe P.T., Lovell-Badge R., Stern C.D. Preventing the loss of competence for neural induction: HGF/SF, L5 and Sox-2. Development. 1997;124:1191–1202.9102306Sunmonu N.A., Li K., Guo Q., Li J.Y.H. Gbx2 and Fgf8 are sequentially required for formation of the midbrain-hindbrain compartment boundary. Development. 2011;138:725–734.PMC302641621266408Tour E., Pillemer G., Gruenbaum Y., Fainsod A. The two Xenopus Gbx2 genes exhibit similar, but not identical expression patterns and can affect head formation. FEBS Lett. 2001;507:205–209.11684099Tour E., Pillemer G., Gruenbaum Y., Fainsod A. Gbx2 interacts with Otx2 and patterns the anterior-posterior axis during gastrulation in Xenopus. Mech. Dev. 2002;112:141–151.11850185Tour E., Pillemer G., Gruenbaum Y., Fainsod A. Otx2 can activate the isthmic organizer genetic network in the Xenopus embryo. Mech. Dev. 2002;110:3–13.11744364Villanueva S., Glavic A., Ruiz P., Mayor R. Posteriorization by FGF, Wnt, and retinoic acid is required for neural crest induction. Dev. Biol. 2002;241:289–301.11784112von Bubnoff A., Schmidt J.E., Kimelman D. The Xenopus laevis homeobox gene Xgbx-2 is an early marker of anteroposterior patterning in the ectoderm. Mech. Dev. 1996;54:149–160.8652408Wada H., Escriva H., Zhang S., Laudet V. Conserved RARE localization in amphioxus Hox clusters and implications for hox code evolution in the vertebrate neural crest. Dev. Dyn. 2006;235:1522–1531.16538655Wakamatsu Y. Mutual repression between Pax3 and Pax6 is involved in the positioning of ophthalmic trigeminal placode in avian embryo. Dev. Growth Differ. 2011;53:994–1003.22111909Wassarman K.M., Lewandoski M., Campbell K., Joyner A.L., Rubenstein J.L., Martinez S., Martin G.R. Specification of the anterior hindbrain and establishment of a normal mid/hindbrain organizer is dependent on Gbx2 gene function. Development. 1997;124:2923–2934.9247335Williams N.A., Holland P.W. Gene and domain duplication in the chordate Otx gene family: insights from amphioxus Otx. Mol. Biol. Evol. 1998;15:600–607.9580990Williams N., Holland P. Old head on young shoulders. Nature. 1996;383:490.Wilson S.W., Houart C. Early steps in the development of the forebrain. Dev. Cell. 2004;6:167–181.PMC278925814960272Xu H., Dude C.M., Baker C.V.H. Fine-grained fate maps for the ophthalmic and maxillomandibular trigeminal placodes in the chick embryo. Dev. Biol. 2008;317:174–186.18367162Zervas M., Millet S., Ahn S., Joyner A.L. Cell behaviors and genetic lineages of the mesencephalon and rhombomere 1. Neuron. 2004;43:345–357.15294143