Development (Cambridge, England)

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0950-1991128212001NovDevelopment (Cambridge, England)Developmentspiel ohne grenzen/pou2 is required during establishment of the zebrafish midbrain-hindbrain boundary organizer.416541764165-76The vertebrate midbrain-hindbrain boundary (MHB) organizes patterning and neuronal differentiation in the midbrain and anterior hindbrain. Formation of this organizing center involves multiple steps, including positioning of the MHB within the neural plate, establishment of the organizer and maintenance of its regional identity and signaling activities. Juxtaposition of the Otx2 and Gbx2 expression domains positions the MHB. How the positional information is translated into activation of Pax2, Wnt1 and Fgf8 expression during MHB establishment remains unclear. In zebrafish spiel ohne grenzen (spg) mutants, the MHB is not established, neither isthmus nor cerebellum form, the midbrain is reduced in size and patterning abnormalities develop within the hindbrain. In spg mutants, despite apparently normal expression of otx2, gbx1 and fgf8 during late gastrula stages, the initial expression of pax2.1, wnt1 and eng2, as well as later expression of fgf8 in the MHB primordium are reduced. We show that spg mutants have lesions in pou2, which encodes a POU-domain transcription factor. Maternal pou2 transcripts are distributed evenly in the blastula, and zygotic expression domains include the midbrain and hindbrain primordia during late gastrulation. Microinjection of pou2 mRNA can rescue pax2.1 and wnt1 expression in the MHB of spg/pou2 mutants without inducing ectopic expression. This indicates an essential but permissive role for pou2 during MHB establishment. pou2 is expressed normally in noi/pax2.1 and ace/fgf8 zebrafish mutants, which also form no MHB. Thus, expression of pou2 does not depend on fgf8 and pax2.1. Our data suggest that pou2 is required for the establishment of the normal expression domains of wnt1 and pax2.1 in the MHB primordium.BeltingH GHGAlbert-Ludwigs-Universität Freiburg, Institut für Biologie I, Hauptstrasse 1, D-79104 Freiburg, Germany.HauptmannGGMeyerDDAbdelilah-SeyfriedSSChitnisAAEschbachCCSöllIIThisseCCThisseBBArtingerK BKBLundeKKDrieverWWengF32 HD008209HDNICHD NIH HHSUnited StatesJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

EnglandDevelopment87017440950-19910DNA-Binding Proteins0Homeodomain Proteins0Nerve Tissue Proteins0Nuclear Proteins0Octamer Transcription Factor-30Otx Transcription Factors0PAX2 Transcription Factor0PAX5 Transcription Factor0PAX8 Transcription Factor0Paired Box Transcription Factors0Pax8 protein, zebrafish0Pou5f3 protein, zebrafish0Proteins0Proto-Oncogene Proteins0Trans-Activators0Transcription Factors0Wnt Proteins0Wnt1 Protein0Zebrafish Proteins0gbx1 protein, zebrafish0otx2b protein, zebrafish0pax2a protein, zebrafish0pax5 protein, zebrafish0wnt8b protein, zebrafish148997-75-5Fibroblast Growth Factor 862031-54-3Fibroblast Growth FactorsIMAnimalsDNA-Binding ProteinsgeneticsEmbryo, NonmammalianFemaleFibroblast Growth Factor 8Fibroblast Growth FactorsgeneticsGastrulaGene Expression Regulation, DevelopmentalHomeodomain ProteinsgeneticsMesencephalonembryologyMutationNerve Tissue ProteinsgeneticsNuclear ProteinsOctamer Transcription Factor-3Organizers, EmbryonicOtx Transcription FactorsPAX2 Transcription FactorPAX5 Transcription FactorPAX8 Transcription FactorPaired Box Transcription FactorsProteinsProto-Oncogene ProteinsgeneticsRhombencephalonembryologyTrans-ActivatorsgeneticsTranscription FactorsgeneticsmetabolismWnt ProteinsWnt1 ProteinZebrafishembryologygeneticsZebrafish Proteins20011031100200215101200110311002014520ppublish11684654NIHMS245363PMC402796010.1242/dev.128.21.4165Acampora D, Avantaggiato V, Tuorto F, Simeone A. Genetic control of brain morphogenesis through Otx gene dosage requirement. Development. 1997;124:3639–3650.9342056Allende ML, Weinberg ES. The expression pattern of two zebrafish achaete-scute homolog (ash) genes is altered in the embryonic brain of the cyclops mutant. Dev. Biol. 1994;166:509–530.7813774Ang SL, Rossant J. Anterior mesendoderm induces mouse engrailed genes in explant cultures. Development. 1993;118:139–149.8375331Araki I, Nakamura H. Engrailed defines the position of dorsal di-mesencephalic boundary by repressing diencephalic fate. Development. 1999;126:5127–5135.10529429Artinger KB, Chitnis AB, Mercola M, Driever W. Zebrafish narrowminded suggests a genetic link between formation of neural crest and primary sensory neurons. Development. 1999;126:3969–3979.PMC405900810457007Blake JA, Eppig JT, Richardson JE, Davisson MT. The Mouse Genome Database (MGD): expanding genetic and genomic resources for the laboratory mouse. Nucleic Acids Res. 2000;28:108–111.PMC10244910592195Brand M, Heisenberg C-P, Jiang Y-J, Beuchle D, Lun K, Furutani-Seiki M, Granato M, Haffter P, Hammerschmidt M, Kane DA, et al. Mutations in zebrafish genes affecting the formation of the boundary between midbrain and hindbrain. Development. 1996;123:179–190.9007239Broccoli V, Boncinelli E, Wurst W. The caudal limit of Otx2 expression positions the isthmic organizer. Nature. 1999;401:164–168.10490025Bulfone A, Puelles L, Proteus MH, Frohman MA, Martin GR, Rubenstein JLR. Spatially restricted expression of Dlx-1, Dlx-2 (Tes-1), Gbx-2, and Wnt-3 in the embryonic day 12.5 mouse forebrain defines potential transverse and longitudinal segmental boundaries. J. Neurosci. 1993;13:3155–3172.PMC65766887687285Crossley PH, Martinez S, Martin GR. Midbrain development induced by FGF8 in the chick embryo. Nature. 1996;380:66–68.8598907Darnell DK, Schoenwolf GC. Vertical induction of Engrailed-2 and other region-specific markers in the early chick embryo. Dev. Dyn. 1997;209:45–58.9142495Driever W, Solnica-Krezel L, Abdelilah S, Meyer D, Stemple D. Genetic analysis of pattern formation in the zebrafish neural plate. Cold Spring Harb. Symp. Quant. Biol. 1997;62:523–534.9598386Funahashi J, Okafuji T, Ohuchi H, Noji S, Tanaka H, Nakamura H. Role of Pax-5 in the regulation of a mid-hindbrain organizer’s activity. Dev. Growth Diff. 1999;41:59–72.10445503Fürthauer M, Thisse C, Thisse B. A role for FGF-8 in the dorsoventral patterning of the zebrafish gastrula. Development. 1997;124:4253–4264.9334274Hauptmann G, Gerster T. Pou-2 – a zebrafish gene active during cleavage stages and in the early hindbrain. Mech. Dev. 1995;51:127–138.7669688Hauptmann G, Gerster T. Complex expression of the zp-50 pou gene in the embryonic zebrafish brain is altered by overexpression of sonic hedgehog. Development. 1996;122:1769–1780.8674416Hauptmann G. Two-color detection of mRNA transcript localizations in fish and fly embryos using alkaline phosphatase and β-galactosidase conjugated antibodies. Dev. Genes Evol. 1999;209:317–321.11252185Heisenberg C-P, Brennan C, Wilson SW. Zebrafish aussicht mutant embryos exhibit widespread overexpression of ace (fgf8) and coincident defects in CNS development. Development. 1999;126:2129–2140.10207138Hemmati-Brivanlou A, Stewart RM, Harland RM. Region-specific neural induction of an engrailed protein by anterior notochord in Xenopus. Science. 1990;250:800–802.1978411Irving C, Mason I. Regeneration of isthmic tissue is the result of a specific and direct interaction between rhombomere 1 and midbrain. Development. 1999;126:3981–3989.10457008Joyner AL, Liu A, Millet S. Otx2, gbx2 and fgf8 interact to position and maintain a mid-hindbrain organizer. Curr. Opin. Cell Biol. 2000;12:736–741.11063941Kelly PD, Chu F, Woods IG, Ngo-Hazelett P, Cardozo T, Huang H, Kimm F, Liao L, Yan YL, Zhou Y, et al. Genetic linkage mapping of zebrafish genes and ESTs. Genome Res. 2000;10:558–567.PMC31085910779498Knapik E, Goodman A, Ekker M, Chevrette M, Delgado J, Neuhauss S, Shimoda N, Driever W, Fishman MC, Jacob HJ. A microsatellite genetic linkage map for zebrafish (Danio rerio) Nat. Genet. 1998;18:338–343.9537415Krauss S, Johansen T, Korzh V, Fjose A. Expression of the zebrafish paired box gene pax[zf-b] during early neurogenesis. Development. 1991;113:1193–1206.1811936Li Y, Allende ML, Finkelstein R, Weinberg ES. Expression of two zebrafish orthodenticle-related genes in the embryonic brain. Mech. Dev. 1994;48:229–244.7893604Liu A, Losos K, Joyner AL. FGF8 can activate Gbx2 and transform regions of the rostral mouse brain into a hindbrain fate. Development. 1999;126:4827–4838.10518499Liu A, Joyner AL. EN and GBX2 play essential roles downstream of FGF8 in patterning the mouse mid/hindbrain region. Development. 2001;128:181–191.11124114Lun K, Brand M. A series of no isthmus (noi) alleles of the zebrafish pax2.1 gene reveals multiple signaling events in development of the midbrain- hindbrain boundary. Development. 1998;125:3049–3062.9671579Marin F, Puelles L. Patterning the embryonic avian midbrain after experimental inversions: a polarizing activity from the isthmus. Dev. Biol. 1994;163:19–37.8174775Marlow F, Zwartkruis F, Malicki J, Neuhauss SCF, Abbas L, Weaver M, Driever W, Solnica-Krezel L. Functional interactions of genes mediating convergent extension, knypek and trilobite during the partitioning of the eye primordium in zebrafish. Dev. Biol. 1998;203:382–399.9808788Martinez S, Wassef M, Alvarado-Mallart R-M. Induction of a mesencephalic phenotype in the 2-day-old chick prosencephalon is preceded by the early expression of the homeobox gene en. Neuron. 1991;6:971–981.1675863Martinez S, Crossley PH, Cobos I, Rubenstein JLR, Martin GR. FGF8 induces formation of an ectopic isthmic organizer and isthmocerebellar development via a repressive effect on Otx2 expression. Development. 1999;126:1189–1200.10021338McMahon AP, Bradley A. The Wnt-1 (int-1) proto-oncogene is required for development of a large region of the mouse brain. Cell. 1990;62:1073–1085.2205396McMahon AP, Joyner AL, Bradley A, McMahon JA. The midbrain-hindbrain phenotype of Wnt-1- / Wnt-1- mice results from stepwise deletion of engrailed-expression cells by 9.5 days post coitum. Cell. 1992;69:581–595.1534034Meyers EN, Lewandoski M, Martin GR. An Fgf8 mutant allelic series generated by Cre- and Flp-mediated recombination. Nat. Genet. 1998;18:136–141.9462741Millet S, Campbell K, Epstein DJ, Losos K, Harris E, Joyner AL. A role for Gbx2 in repression of Otx2 and positioning the mid/hindbrain organizer. Nature. 1999;401:161–164.10490024Molven A, Njolstad PR, Fjose A. Genomic structure and restricted neural expression of the zebrafish wnt-1 (int-1) gene. EMBO J. 1991;10:799–807.PMC4527192009859Nasevicius A, Ekker SC. Effective targeted gene ‘knockdown’ in zebrafish. Nat. Genet. 2000;26:216–220.11017081Okafuji T, Funahashi J, Nakamura H. Roles of Pax-2 in initiation of the chick tectal development. Dev. Brain Res. 1999;116:41–49.10446345Patarnello T, Bargelloni L, Boncinelli E, Spada F, Pannese M, Broccoli V. Evolution of Emx genes and brain development in vertebrates. Proc. R. Soc. London B Biol. Sci. 1997;264:1763–1766.PMC16887499447733Pesce M, Gross MK, Schöler HR. In line with our ancestors: Oct-4 and the mammalian germ. BioEssays. 1998;20:722–732.9819561Pfeffer PL, Gerster T, Lun K, Brand M, Busslinger M. Characterization of three novel members of the zebrafis Pax2/5/8 family: dependency of Pax5 and Pax8 expression on the Pax2.1 (noi) function. Development. 1998;125:3063–3074.9671580Pfeffer PL, Bouchard M, Busslinger M. Pax2 and homeodomain proteins cooperatively regulate a 435 bp enhancer of the mouse Pax5 gene at the midbrain-hindbrain boundary. Development. 2000;127:1017–1028.10662641Postlethwait JH, Yan Y-L, Gates MA, Horne S, Amores A, Brownlie A, Donovan A, Egan ES, Force A, Gong Z, et al. Vertebrate genome evolution and the zebrafish gene map. Nat. Genet. 1998;18:345–349.9537416Qian YQ, Billeter M, Otting G, Müller M, Gehring WJ, Wüthrich K. The structure of the antennapedia homeodomain determined by NMR spectroscopy in solution: comparison with prokaryotic repressors. Cell. 1989;59:573–580.2572329Reifers F, Böhli H, Walsh EC, Crossley PH, Stainier DY, Brand M. Fgf8 is mutated in zebrafish acerebellar (ace) mutants and is required for maintenance of midbrain-hindbrain boundary development and somitogenesis. Development. 1998;125:2381–2395.9609821Rhinn M, Brand M. The midbrain-hindbrain boundary organizer. Curr. Opin. Neurobiol. 2001;11:34–42.11179870Ristoratore F, Carl M, Deschet K, Richard-Parpaillon L, Boujard D, Wittbrodt J, Chourrout D, Bourrat F, Joly J-S. The midbrain-hindbrain boundary genetic cascade is activated ectopically in the diencephalon in response to the widespread expression of one of its components, the medaka gene Ol-eng2. Development. 1999;126:3769–3779.10433907Rowitch DH, McMahon AP. Pax-2 expression in the murine neural plate precedes and encompasses the expression domains of Wnt-1 and En-1. Mech. Dev. 1995;52:3–8.7577673Ryan AK, Rosenfeld MG. POU domain family values: flexibility, partnerships, and developmental codes. Genes Dev. 1997;11:1207–1225.9171367Schier AF, Neuhauss SCF, Harvey M, Malicki J, Solnica-Krezel L, Stainier DYR, Zwartkruis F, Abdelilah S, Stemple DL, Rangini Z, et al. Mutations affecting the development of the embryonic zebrafish brain. Development. 1996;123:165–178.9007238Schöler HR, Hatzopoulos AK, Balling R, Suzuki N, Gruss P. A family of octamer-specific proteins present during mouse embryogenesis: evidence for germline-specific expression of an Oct factor. EMBO J. 1989;8:2543–2550.PMC4012522573523Schwarz M, Alvarez-Bolado G, Urbánek P, Busslinger M, Gruss P. Conserved biological function between Pax-2 and Pax-5 in midbrain and cerebellum development: Evidence in targeted mutations. Proc. Natl. Acad. Sci. USA. 1997;94:14518–14523.PMC250409405645Scott MP, Tamkun JW, Hartzell GW. The structure and function of the homeodomain. Biochim. Biophys. Acta. 1989;989:25–48.2568852Shamim H, Mahmood R, Logan C, Doherty P, Lumsden A, Mason I. Sequential roles for Fgf4, En1 and Fgf8 in specification and regionalisation of the midbrain. Development. 1999;126:945–959.9927596Shimoda N, Knapik EW, Ziniti J, Sim C, Yamada E, Kaplan S, Jackson D, de Sauvage F, Jacob H, Fishman MC. Zebrafish genetic map with 2000 microsatellite markers. Genomics. 1999;58:219–232.10373319Song DL, Chalepakis G, Gruss P, Joyner AL. Two Pax binding sites are required for early embryonic brain expression of an Engrailed-2 transgene. Development. 1996;122:627–635.8625814Takeda H, Matsuzaki T, Oki T, Miyagawa T, Amanuma H. A novel POU domain gene, zebrafish pou2: expression and roles of two alternatively spliced twin products in early development. Genes Dev. 1994;8:45–59.8288127Urbanek P, Wang ZQ, Fetka I, Wagner EF, Busslinger M. Complete block of early B-cell differentiation and altered patterning of the posterior midbrain in mice lacking Pax5/BSAP. Cell. 1994;79:901–912.8001127Vos P, Hogers R, Bleeker M, Reijans M, van de Lee T, Hornes M, Frijters A, Pot J, Peleman J, Kuiper M, et al. AFLP: a new technique for DNA fingerprinting. Nucleic Acids Res. 1995;23:4407–4414.PMC3073977501463Wassarman KM, Lewandoski M, Campbell K, Joyner AL, Rubenstein JLR, Martinez S, Martin GR. Specification of the anterior hindbrain and establishment of a normal mid/hindbrain organizer is dependent on Gbx2 gene function. Development. 1997;124:2923–2934.9247335Wassef M, Joyner AL. Early mesencephalon/metencephalon patterning and development of the cerebellum. Perspect. Dev. Neurobiol. 1997;5:3–16.9509514Westerfield M. The Zebrafish Book. Eugene, OR: University of Oregon Press; 1994.Woods IG, Kelly PD, Chu F, Ngo-Hazelett P, Yan YL, Huang H, Postlethwait JH, Talbot WS. A comparative map of the zebrafish genome. Genome Res. 2000;10:1903–1914.PMC31307011116086Wurst W, Auerbach AB, Joyner AL. Multiple developmental defects in Engrailed-1 mutant mice: an early mid-hindbrain deletion and patterning defects in forelimbs and sternum. Development. 1994;120:2065–2075.7925010