The product of the split ends gene is required for the maintenance of positional information during Drosophila development

BMC Developmental Biology

Antonio Tugores²  Kimberly Mace¹ 

[1] Department of Biology, 0349. University of California, San Diego. 9500 Gilman Dr., La Jolla, CA 92093, USA;Almirall Prodesfarma SA, Cardener 68, 08024 Barcelona, SPAIN

Others  :  1173662
DOI  :  10.1186/1471-213X-4-15

 received in 2004-07-27, accepted in 2004-12-13,  发布年份 2004

【 摘 要 】

Background

The Drosophila split ends (spen) gene encodes a large nuclear protein containing three RNP-type RNA binding motifs, and a conserved transcriptional co-repressor-interacting domain at the C-terminus. Genetic analyses indicate that spen interacts with pathways that regulate the function of Hox proteins, the response to various signaling cascades and cell cycle control. Although spen mutants affect only a small subset of morphological structures in embryos, it has been difficult to find a common theme in spen mutant structural alterations, or in the interactions of spen with known signaling pathways.

Results

By generating clones of spen mutant cells in wing imaginal discs, we show that spen function is required for the correct formation and positioning of veins and mechanosensory bristles both on the anterior wing margin and on the notum, and for the maintenance of planar polarity. Wing vein phenotypic alterations are enhanced by mutations in the crinkled (ck) gene, encoding a non-conventional myosin, and correlate with an abnormal spatial expression of Delta, an early marker of vein formation in third instar wing imaginal discs. Positioning defects were also evident in the organization of the embryonic peripheral nervous system, accompanied by abnormal E-Cadherin expression in the epidermis.

Conclusions

The data presented indicate that the role of spen is necessary to maintain the correct positioning of cells within a pre-specified domain throughout development. Its requirement for epithelial planar polarity, its interaction with ck, and the abnormal E-Cadherin expression associated with spen mutations suggest that spen exerts its function by interacting with basic cellular mechanisms required to maintain multicellular organization in metazoans. This role for spen may explain why mutations in this gene interact with the outcome of multiple signaling pathways.

【 授权许可】

   
2004 Mace and Tugores; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Kolodziej PA, Jan LY, Jan YN: Mutations that affect the length, fasciculation, or ventral orientation of specific sensory axons in the Drosophila embryo. Neuron 1995, 15:273-286.
• [2]Gellon G, Harding KW, McGinnis N, Martin M, McGinnis W: A genetic screen for modifiers of Deformed homeotic function identifies novel genes required for head development. Development 1997, 124:3321-3331.
• [3]Wiellette EL, Harding KW, Mace KA, Ronshaugen MR, Wang FY, McGinnis W: spen encodes an RNP motif protein that interacts with Hox pathways to repress the development of head-like sclerites in the Drosophila trunk. Development 1999, 126:5373-5385.
• [4]Dickson BJ, Van Der Straten A, Domínguez M, Hafen E: Mutations modulating Raf signaling in Drosophila eye development. Genetics 1996, 142:163-171.
• [5]Therrien M, Morrison DK, Wong AM, Rubin GM: A genetic screen for modifiers of a kinase suppressor of Ras-dependent rough eye phenotype in Drosophila. Genetics 2000, 156:1231-1242.
• [6]Firth L, Manchester J, Lorenzen JA, Baron M, Perkins LA: Identification of genomic regions that interact with a viable allele of the Drosophila protein tyrosine phosphatase corkscrew. Genetics 2000, 156:733-748.
• [7]Rebay I, Chen F, Hsiao F, Kolodziej PA, Kuang BH, Laverty T, Suh C, Voas M, Williams A, Rubin GM: A genetic screen for novel components of the Ras/Mitogen-Activated Protein Kinase signaling pathway that interact with the yan gene of Drosophila identifies split ends, a new RNA recognition motif-containing protein. Genetics 2000, 154:695-712.
• [8]Chen F, Rebay I: split ends, a new component of the Drosophila EGF receptor pathway, regulates development of midline glial cells. Curr Biol 2000, 10:943-946.
• [9]Staehling-Hampton K, Ciampa PJ, Brook A, Dyson N: A genetic screen for modifiers of E2F in Drosophila melanogaster. Genetics 1999, 153:275-287.
• [10]Lane ME, Elend M, Heidman D, Herr A, Marzodko S, Herzig A, Lehner CF: A screen for modifiers of Cyclin E function in Drosophila melanogaster identifies Cdk2 mutations, revealing the insignificance of putative phosphorylation sites in Cdk2. Genetics 2000, 155:233-244.
• [11]Abdelilah-Seyfried S, Chan Y-M, Zeng C, Justice NJ, Younger-Shepherd S, Sharp LE, Barbel S, Meadows SA, Jan LY, Jan YN: A gain-of-function screen for genes that affect the development of the Drosophila adult external sensory organ. Genetics 2000, 155:733-752.
• [12]Kuang B, Wu SC, Shin Y, Luo L, Kolodziej P: split ends encodes large nuclear proteins that regulate neuronal cell fate and axon extension in the Drosophila embryo. Development 2000, 127:1517-1529.
• [13]Lin HV, Doroquez DB, Cho S, Chen F, Rebay I, Cadigan KM: Split ends is a tissue/promoter specific regulator of Wingless signaling. Development 2003, 130:3125-3135.
• [14]Newberry EP, Latifi T, Towler DA: The RRM domain of MINT, a novel Msx2 binding protein, recognizes and regulates the osteocalcin promoter. Biochemistry 1999, 38:10678-10690.
• [15]Shi Y, Downes M, Xie W, Kao H-Y, Ordentlich P, Tsai C-C, Hon M, Evans RM: Sharp, an inducible cofactor that integrates nuclear receptor repression and activation. Genes Dev 2001, 15:1140-1151.
• [16]Ariyoshi M, Schwabbe JW: A conserved structural motif reveals the essential transcriptional repression function of Spen proteins and their role in developmental signaling. Genes Dev 2003, 17:1909-1920.
• [17]Oswald F, Kostezka U, Astrahantseff K, Bourteele S, Dillinger K, Zechner U, Ludwig L, Wilda M, Hameister H, Knöchel W, Liptay S, Schmid RM: SHARP is a novel component of the Notch/RBP-Jκ signaling pathway. EMBO J 2002, 21:5417-5426.
• [18]Kuroda K, Han H, Tani S, Tanigaki K, Tun T, Furukawa T, Taniguchi Y, Kurooka H, Hamada Y, Toyokuni S, Honjo T: Regulation of marginal zone B cell development by MINT, a suppressor of Notch/RBP-J signaling pathway. Immunity 2003, 18:301-312.
• [19]Sturtevant MA, Bier E: Analysis of the genetic hierarchy guiding wing vein development in Drosophila. Development 1995, 121:785-801.
• [20]Neufeld TP, de la Cruz AF, Johnston LA, Edgar BA: Coordination of growth and cell division in the Drosophila wing. Cell 1998, 93:1183-1193.
• [21]Xu T, Rubin GM: Analysis of genetic mosaics in developing and adult Drosophila tissues. Development 1993, 117:1223-1237.
• [22]Capdevila J, Guerrero I: Targeted expression of the signaling molecule decapentaplegic induces pattern duplications and growth alterations in Drosophila wings. EMBO J 1994, 13:4459-4468.
• [23]Duffy JB, Harrison DA, Perrimon N: Identifying loci required for follicular patterning using directed mosaics. Development 1998, 125:2263-2271.
• [24]Jack JW, Dorsett D, DeLotto Y, Liu S: Expression of the cut locus in the Drosophila wing margin is required for cell type specification and is regulated by a distal enhancer. Development 1991, 113:735-747.
• [25]Blochlinger K, Jan LY, Jan YN: Postembryonic patterns of expression of cut, a locus regulating sensory organ identity in Drosophila. Development 1993, 117:441-450.
• [26]Neumann CJ, Cohen SM: A hierarchy of cross-regulation involving Notch, wingless, vestigial and cut organizes de dorsal/ventral axis of the Drosophila wing. Development 1996, 124:1485-1495.
• [27]Micchelli CA, Rulifson EJ, Blair SS: The function and regulation of cut expression on the wing margin of Drosophila: Notch, wingless and a dominant negative role for Delta and Serrate. Development 1997, 124:1485-1495.
• [28]Staehling-Hampton K, Jackson PD, Clark MJ, Brand AH, Hoffmann FM: Specificity of bone morphogenetic protein-related factors: cell fate and gene expression changes in Drosophila embryos induced by decapentaplegic but not 60A. Cell Growth Diffn 1994, 5:585-593.
• [29]Lai EC, Orgogozo V: A hidden program in Drosophila peripheral neurogenesis revealed: fundamental principles underlying sensory organ diversity. Dev Biol 2004, 269:1-17.
• [30]Tepass U, Gruszynski-DeFeo E, Haag TA, Omatyar L, Torok T, Hartenstein V: shotgun encodes Drosophila E-cadherin and is preferentially required during cell rearrangement in the neurectoderm and other morphogenetically active epithelia. Genes Dev 1996, 10:672-685.
• [31]Guichard A, Biehs B, Sturtevant MA, Wickline L, Chako J, Howard K, Bier E: rhomboid and Star interact synergistically to promote EGFR/MAPK signaling during Drosophila wing vein development. Development 1999, 126:2663-2676.
• [32]Freeman M: Reiterative use of the EGF receptor triggers differentiation of all cell types in the Drosophila eye. Cell 1996, 87:651-660.
• [33]Gabay L, Scholz H, Golembo M, Klaes A, Shilo BZ, Klambt C: EGF receptor signaling induces pointed P1 transcription and inactivates Yan protein in the Drosophila embryonic ventral ectoderm. Development 1996, 122:3355-3362.
• [34]Lai EC: Keeping a good pathway down: transcriptional repression of Notch pathway target genes by CSL proteins. EMBO Rep 2002, 3:840-845.
• [35]Cinamon G, Matloubian M, Lesneski MJ, Xu Y, Low C, Lu T, Proia RL, Cyster JG: Sphingosine 1-phosphate receptor 1 promotes B cell localization in the splenic marginal zone. Nat Immunol 2004, 5:713-720.
• [36]Artavanis-Tsakonas S, Rand MD, Lake RJ: Notch signaling: Cell fate control and signal integration in development. Science 1999, 284:770-776.
• [37]Lai EC, Bodner R, Kavaler J, Freschi G, Posakony JW: Antagonism of notch signaling activity by members of a novel protein family encoded by the bearded and enhancer of split gene complexes. Development 2000, 127:291-306.
• [38]Nolo R, Abbott LA, Bellen HJ: Senseless, a Zn finger transcription factor, is necessary and sufficient for sensory organ development in Drosophila. Cell 2000, 102:349-362.
• [39]Dumstrei K, Wang F, Shy D, Tepass U, Hartenstein V: Interaction between EGFR signaling and DE-cadherin during nervous system morphogenesis. Development 2002, 129:3983-3994.
• [40]Adler PN, Charlton J, Liu J: Mutations in the cadherin superfamily member gene daschous cause a tissue polarity phenotype by altering frizzled signaling. Development 1998, 125:959-968.
• [41]Kussel-Andermann P, El-Amraoui A, Safieddine S, Nouaille S, Perfettini I, Lecuit M, Cossart P, Wolfrum U, Petit C: Vezatin, a novel transmembrane protein, bridges myosin VIIA to the cadherin-catenins complex. EMBO J 2000, 19:6020-6029.
• [42]Winter CG, Wang B, Ballew A, Royou A, Karess R, Axelrod JD, Luo L: Drosophila Rho-associated kinase (Drok) links Frizzled-mediated planar cell polarity signaling to the actin cytoskeleton. Cell 2001, 105:81-91.
• [43]Levy G, Levi-Acobas F, Blanchard S, Gerber S, Larget-Piet D, Chenal V, Liu X.-Z, Newton V, Steel KP, Brown SDM., Munnich A, Kaplan J, Petit C, Weil D: Myosin VIIA gene: heterogeneity of the mutations responsible for Usher syndrome type IB. Hum Molec Genet 1997, 6:111-116.
• [44]Gibson F, Walsh J, Mburu P, Varela A, Brown KA, Antonio M, Beisel KW, Steel KP, Brown SDM: A type VII myosin encoded by the mouse deaffness gene shaker-1. Nature 1995, 374:62-64.
• [45]Ernest S, Rauch G-J, Haffter P, Geisler R, Petit C, Nicolson T: Mariner is defective in myosin VIIA: a zebrafish model for human hereditary deaffness. Hum Molec Genet 2000, 9:2189-2196.
• [46]Ensembl Genome Server [http://www.ensembl.org/] webcite
• [47]National Center for Biotechnology Information [http://www.ncbi.nlm.nih.gov/] webcite
• [48]Ma Z, Morris SW, Valentine V, Li M, Herbrick JA, Cui X, Bouman D, Li Y, Mehta PK, Nizetic D, Kaneko Y, Chan GC, Chan LC, Squire J, Scherer SW, Hitzler JK: Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia. Nat Genet 2001, 28:220-221.
• [49]Mercher T, Busson Le-Coniat M, Monni R, Mauchauffé M, Khac FN, Gressin L, Mugneret F, Leblanc T, Dastugue N, Berger R, Bernard OA: Involvement of a human gene related to the Drosophila spen gene in the recurrent t(1;22) translocation of acute megacaryocytic leukemia. Proc Natl Acad Sci USA 2001, 98:5776-5779.
• [50]Chou TB, Perrimon N: The autosomal FLP-DFS technique for generating germline mosaics in Drosophila melanogaster. Genetics 1996, 144:1673-1679.
• [51]Qi H, Rand MD, Wu X, Sestan N, Wang W, Rakic P, Xu T, Artavanis-Tsakonas S: Processing of the Notch ligand Delta by the metalloprotease Kuzbanian. Science 1999, 283:91-94.
• [52]Zipursky SL, Venkatesh TR, Teplow DB, Benzer S: Neuronal development in the Drosophila retina: monoclonal antibodies as molecular probes. Cell 1984, 36:15-26.
• [53]Blochlinger K, Bodmer R, Jan LY, Jan YN: Patterns of expression of Cut, a protein required for externalsensory organ development in wild-type and cut mutant Drosophila embryos. Genes Dev 1990, 4:1322-1331.
• [54]Oda H, Uemura T, Harada Y, Iwai Y, Takeichi M: A Drosophila homolog of cadherin associated with armadillo and essential forembryonic cell-cell adhesion. Dev Biol 1994, 165:716-726.
• [55]Patel N: Imaging neuronal subsets and other cell types in whole-mount Drosophila embryos and larvae using antibody probes. Methods Cell Biol 1994, 44:445-487.
• [56]O'Neill EM, Rebay I, Tjian R, Rubin GM: The activities of two ETS-related transcription factors required for Drosophila eye development are modulated by the Ras/MAPK pathway. Cell 1994, 78:137-147.
• [57]Wieschaus E, Nusslein-Volhard C: Looking at Embryos. In In Drosophila, a practical approach. Edited by Roberts DB. Oxford: IRL Press Limited; 1986:199-227.
• [58]Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ: Basic local alignment search tool. J Mol Biol 1990, 215:403-410.
• [59]Schuler GD, Altschul SF, Lipman DJ: A Workbench for Multiple Alignment Construction and Analysis. Proteins Struct Funct Genet 1991, 9:180-190.
• [60]Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F, Higgins DG: The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 1997, 25:4876-4882.
• [61]Burge C, Karlin S: Prediction of complete gene structures in human genomic DNA. J Mol Biol 1997, 268:78-94.