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Odd-Paired: The Drosophila Zic Gene

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Zic family

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1046))

Abstract

Zinc finger in the cerebellum (Zic) proteins are a family of transcription factors with multiple roles during development, particularly in neural tissues. The founding member of the Zic family is the Drosophila odd-paired (opa) gene. The Opa protein has a DNA binding domain containing five Cys2His2-type zinc fingers and has been shown to act as a sequence-specific DNA binding protein. Opa has significant homology to mammalian Zic1, Zic2, and Zic3 within the zinc finger domain and in two other conserved regions outside that domain. opa was initially identified as a pair-rule gene, part of the hierarchy of genes that establish the segmental body plan of the early Drosophila embryo. However, its wide expression pattern during embryogenesis indicates it plays additional roles. Embryos deficient in opa die before hatching with aberrant segmentation but also with defects in larval midgut formation. Post-embryonically, opa plays important roles in adult head development and circadian rhythm. Based on extensive neural expression, opa is predicted to be involved in many aspects of neural development and behavior, like other proteins of the Zic family. Consensus DNA binding sites have been identified for Opa and have been shown to activate transcription in vivo. However, there is evidence Opa may serve as a transcriptional regulator in the absence of direct DNA binding, as has been seen for other Zic proteins.

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References

  • Alexandre C, Jacinto A, Ingham PW (1996) Transcriptional activation of hedgehog target genes in Drosophila is mediated directly by the cubitus interruptus protein, a member of the GLI family of zinc finger DNA-binding proteins. Genes Dev 10(16):2003–2013

    Article  CAS  PubMed  Google Scholar 

  • Aruga J (2004) The role of Zic genes in neural development. Mol Cell Neurosci 26(2):205–221

    Article  CAS  PubMed  Google Scholar 

  • Aruga J, Nagai T, Tokuyama T, Hayashizaki Y, Okazaki Y, Chapman VM, Mikoshiba K (1996) The mouse zic gene family. Homologues of the Drosophila pair-rule gene odd-paired. J Biol Chem 271(2):1043–1047

    Article  CAS  PubMed  Google Scholar 

  • Aruga J, Kamiya A, Takahashi H, Fujimi TJ, Shimizu Y, Ohkawa K, Yazawa S, Umesono Y, Noguchi H, Shimizu T, Saitou N, Mikoshiba K, Sakaki Y, Agata K, Toyoda A (2006) A wide-range phylogenetic analysis of Zic proteins: implications for correlations between protein structure conservation and body plan complexity. Genomics 87(6):783–792. https://doi.org/10.1016/j.ygeno.2006.02.011

    Article  CAS  PubMed  Google Scholar 

  • Arya GH, Magwire MM, Huang W, Serrano-Negron YL, Mackay TF, Anholt RR (2015) The genetic basis for variation in olfactory behavior in Drosophila melanogaster. Chem Senses 40(4):233–243. https://doi.org/10.1093/chemse/bjv001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Azpiazu N, Lawrence PA, Vincent JP, Frasch M (1996) Segmentation and specification of the Drosophila mesoderm. Genes Dev 10(24):3183–3194

    Article  CAS  PubMed  Google Scholar 

  • Benedyk MJ, Mullen JR, Dinardo S (1994) Odd-paired – a zinc-finger pair rule protein required for the timely activation of engrailed and wingless in drosophila embryos. Genes Dev 8(1):105–117

    Article  CAS  PubMed  Google Scholar 

  • Bilder D, Scott MP (1998) Hedgehog and wingless induce metameric pattern in the Drosophila visceral mesoderm. Dev Biol 201(1):43–56. https://doi.org/10.1006/dbio.1998.8953

    Article  CAS  PubMed  Google Scholar 

  • Bilder D, Graba Y, Scott MP (1998) Wnt and TGFbeta signals subdivide the AbdA Hox domain during Drosophila mesoderm patterning. Development 125(9):1781–1790

    CAS  PubMed  Google Scholar 

  • Brown SA, Warburton D, Brown LY, Yu CY, Roeder ER, Stengel-Rutkowski S, Hennekam RCM, Muenke M (1998) Holoprosencephaly due to mutations in ZIC2, a homologue of Drosophila odd-paired. Nat Genet 20(2):180–183

    Article  CAS  PubMed  Google Scholar 

  • Butler MJ, Jacobsen TL, Cain DM, Jarman MG, Hubank M, Whittle JR, Phillips R, Simcox A (2003) Discovery of genes with highly restricted expression patterns in the Drosophila wing disc using DNA oligonucleotide microarrays. Development 130(4):659–670

    Article  CAS  PubMed  Google Scholar 

  • Chintapalli VR, Wang J, Dow JA (2007) Using FlyAtlas to identify better Drosophila melanogaster models of human disease. Nat Genet 39(6):715–720. https://doi.org/10.1038/ng2049

    Article  CAS  PubMed  Google Scholar 

  • Cimbora DM, Sakonju S (1995) Drosophila midgut morphogenesis requires the function of the segmentation gene odd-paired. Dev Biol 169(2):580–595

    Article  CAS  PubMed  Google Scholar 

  • Clark E, Akam M (2016) Odd-paired controls frequency doubling in Drosophila segmentation by altering the pair-rule gene regulatory network. Elife 5. https://doi.org/10.7554/eLife.18215

  • Dubourg C, Bendavid C, Pasquier L, Henry C, Odent S, David V (2007) Holoprosencephaly. Orphanet J Rare Dis 2:8

    Article  PubMed  PubMed Central  Google Scholar 

  • Eroglu E, Burkard TR, Jiang Y, Saini N, Homem CC, Reichert H, Knoblich JA (2014) SWI/SNF complex prevents lineage reversion and induces temporal patterning in neural stem cells. Cell 156(6):1259–1273. https://doi.org/10.1016/j.cell.2014.01.053

    Article  CAS  PubMed  Google Scholar 

  • Fernandes M, Hebert JM (2008) The ups and downs of holoprosencephaly: dorsal versus ventral patterning forces. Clin Genet 73(5):413–423. https://doi.org/10.1111/j.1399-0004.2008.00994.x

    Article  CAS  PubMed  Google Scholar 

  • Fernandes M, Gutin G, Alcorn H, McConnell SK, Hebert JM (2007) Mutations in the BMP pathway in mice support the existence of two molecular classes of holoprosencephaly. Development 134(21):3789–3794. https://doi.org/10.1242/dev.004325

    Article  CAS  PubMed  Google Scholar 

  • Fujimi TJ, Hatayama M, Aruga J (2012) Xenopus Zic3 controls notochord and organizer development through suppression of the Wnt/beta-catenin signaling pathway. Dev Biol 361(2):220–231. https://doi.org/10.1016/j.ydbio.2011.10.026

    Article  CAS  PubMed  Google Scholar 

  • Graba Y, Aragnol D, Pradel J (1997) Drosophila Hox complex downstream targets and the function of homeotic genes. BioEssays 19(5):379–388

    Article  CAS  PubMed  Google Scholar 

  • Graveley BR, Brooks AN, Carlson JW, Duff MO, Landolin JM, Yang L, Artieri CG, van Baren MJ, Boley N, Booth BW, Brown JB, Cherbas L, Davis CA, Dobin A, Li R, Lin W, Malone JH, Mattiuzzo NR, Miller D, Sturgill D, Tuch BB, Zaleski C, Zhang D, Blanchette M, Dudoit S, Eads B, Green RE, Hammonds A, Jiang L, Kapranov P, Langton L, Perrimon N, Sandler JE, Wan KH, Willingham A, Zhang Y, Zou Y, Andrews J, Bickel PJ, Brenner SE, Brent MR, Cherbas P, Gingeras TR, Hoskins RA, Kaufman TC, Oliver B, Celniker SE (2011) The developmental transcriptome of Drosophila melanogaster. Nature 471(7339):473–479. https://doi.org/10.1038/nature09715

    Article  CAS  PubMed  Google Scholar 

  • Grinberg I, Millen KJ (2005) The ZIC gene family in development and disease. Clin Genet 67(4):290–296

    Article  CAS  PubMed  Google Scholar 

  • Hardin PE (2011) Molecular genetic analysis of circadian timekeeping in Drosophila. Adv Genet 74:141–173. https://doi.org/10.1016/B978-0-12-387690-4.00005-2

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hepker J, Blackman RK, Holmgren R (1999) Cubitus interruptus is necessary but not sufficient for direct activation of a wing-specific decapentaplegic enhancer. Development 126(16):3669–3677

    CAS  PubMed  Google Scholar 

  • Jaynes JB, Fujioka M (2004) Drawing lines in the sand: even skipped et al. and parasegment boundaries. Dev Biol 269(2):609–622. https://doi.org/10.1016/j.ydbio.2004.03.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jurgens G, Wieschaus E, Nussleinvolhard C, Kluding H (1984) Mutations affecting the pattern of the larval cuticle in Drosophila-melanogaster. 2. Zygotic loci on the 3rd chromosome. Wilhelm Rouxs Arch DevBiol 193(5):283–295

    Article  CAS  Google Scholar 

  • Kinzler KW, Vogelstein B (1990) The GLI gene encodes a nuclear protein which binds specific sequences in the human genome. Mol Cell Biol 10(2):634–642

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Konopka RJ, Benzer S (1971) Clock mutants of Drosophila melanogaster. Proc Natl Acad Sci U S A 68(9):2112–2116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koyabu Y, Nakata K, Mizugishi K, Aruga J, Mikoshiba K (2001) Physical and functional interactions between Zic and Gli proteins. J Biol Chem 276(10):6889–6892

    Article  CAS  PubMed  Google Scholar 

  • Layden MJ, Meyer NP, Pang K, Seaver EC, Martindale MQ (2010) Expression and phylogenetic analysis of the zic gene family in the evolution and development of metazoans. EvoDevo 1(1):12. https://doi.org/10.1186/2041-9139-1-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee H, Stultz BG, Hursh DA (2007) The Zic family member, odd-paired, regulates the Drosophila BMP, decapentaplegic, during adult head development. Development 134(7):1301–1310

    Article  CAS  PubMed  Google Scholar 

  • Lichti-Kaiser K, ZeRuth G, Kang HS, Vasanth S, Jetten AM (2012) Gli-similar proteins: their mechanisms of action, physiological functions, and roles in disease. Vitam Horm 88:141–171. https://doi.org/10.1016/B978-0-12-394622-5.00007-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lim LS, Hong FH, Kunarso G, Stanton LW (2010) The pluripotency regulator Zic3 is a direct activator of the Nanog promoter in ESCs. Stem Cells 28(11):1961–1969. https://doi.org/10.1002/stem.527

    Article  CAS  PubMed  Google Scholar 

  • Luo Z, Gao X, Lin C, Smith ER, Marshall SA, Swanson SK, Florens L, Washburn MP, Shilatifard A (2015) Zic2 is an enhancer-binding factor required for embryonic stem cell specification. Mol Cell 57(4):685–694. https://doi.org/10.1016/j.molcel.2015.01.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mahoney MB, Parks AL, Ruddy DA, Tiong SY, Esengil H, Phan AC, Philandrinos P, Winter CG, Chatterjee R, Huppert K, Fisher WW, L’Archeveque L, Mapa FA, Woo W, Ellis MC, Curtis D (2006) Presenilin-based genetic screens in Drosophila melanogaster identify novel notch pathway modifiers. Genetics 172(4):2309–2324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meireles-Filho AC, Bardet AF, Yanez-Cuna JO, Stampfel G, Stark A (2014) cis-regulatory requirements for tissue-specific programs of the circadian clock. Curr Biol 24(1):1–10. https://doi.org/10.1016/j.cub.2013.11.017

    Article  CAS  PubMed  Google Scholar 

  • Merzdorf CS (2007) Emerging roles for zic genes in early development. Dev Dyn 236(4):922–940. https://doi.org/10.1002/dvdy.21098

    Article  CAS  PubMed  Google Scholar 

  • Ming JE, Muenke M (2002) Multiple hits during early embryonic development: digenic diseases and holoprosencephaly. Am J Hum Genet 71(5):1017–1032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mizugishi K, Aruga J, Nakata K, Mikoshiba K (2001) Molecular properties of Zic proteins as transcriptional regulators and their relationship to GLI proteins. J Biol Chem 276(3):2180–2188

    Article  CAS  PubMed  Google Scholar 

  • Mizugishi K, Hatayama M, Tohmonda T, Ogawa M, Inoue T, Mikoshiba K, Aruga J (2004) Myogenic repressor I-mfa interferes with the function of Zic family proteins. Biochem Biophys Res Commun 320(1):233–240. https://doi.org/10.1016/j.bbrc.2004.05.158

    Article  CAS  PubMed  Google Scholar 

  • Moore LA, Broihier HT, Van Doren M, Lunsford LB, Lehmann R (1998) Identification of genes controlling germ cell migration and embryonic gonad formation in Drosophila. Development 125(4):667–678

    CAS  PubMed  Google Scholar 

  • Muenke M, Beachy PA (2000) Genetics of ventral forebrain development and holoprosencephaly. Curr Opin Genet Dev 10(3):262–269

    Article  CAS  PubMed  Google Scholar 

  • Murgan S, Kari W, Rothbacher U, Iche-Torres M, Melenec P, Hobert O, Bertrand V (2015) Atypical transcriptional activation by TCF via a Zic transcription factor in C. elegans neuronal precursors. Dev Cell 33(6):737–745. https://doi.org/10.1016/j.devcel.2015.04.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Negre N, Brown CD, Ma L, Bristow CA, Miller SW, Wagner U, Kheradpour P, Eaton ML, Loriaux P, Sealfon R, Li Z, Ishii H, Spokony RF, Chen J, Hwang L, Cheng C, Auburn RP, Davis MB, Domanus M, Shah PK, Morrison CA, Zieba J, Suchy S, Senderowicz L, Victorsen A, Bild NA, Grundstad AJ, Hanley D, MacAlpine DM, Mannervik M, Venken K, Bellen H, White R, Gerstein M, Russell S, Grossman RL, Ren B, Posakony JW, Kellis M, White KP (2011) A cis-regulatory map of the Drosophila genome. Nature 471(7339):527–531. https://doi.org/10.1038/nature09990

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nitta KR, Jolma A, Yin Y, Morgunova E, Kivioja T, Akhtar J, Hens K, Toivonen J, Deplancke B, Furlong EE, Taipale J (2015) Conservation of transcription factor binding specificities across 600 million years of bilateria evolution. Elife 4. https://doi.org/10.7554/eLife.04837

  • Noyes MB, Meng X, Wakabayashi A, Sinha S, Brodsky MH, Wolfe SA (2008) A systematic characterization of factors that regulate Drosophila segmentation via a bacterial one-hybrid system. Nucleic Acids Res 36(8):2547–2560. https://doi.org/10.1093/nar/gkn048

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pavletich NP, Pabo CO (1993) Crystal structure of a five-finger GLI-DNA complex: new perspectives on zinc fingers. Science 261(5129):1701–1707

    Article  CAS  PubMed  Google Scholar 

  • Petryk A, Graf D, Marcucio R (2015) Holoprosencephaly: signaling interactions between the brain and the face, the environment and the genes, and the phenotypic variability in animal models and humans. Wiley Interdiscip Rev Dev Biol 4(1):17–32. https://doi.org/10.1002/wdev.161

    Article  CAS  PubMed  Google Scholar 

  • Pfeiffer BD, Jenett A, Hammonds AS, Ngo TT, Misra S, Murphy C, Scully A, Carlson JW, Wan KH, Laverty TR, Mungall C, Svirskas R, Kadonaga JT, Doe CQ, Eisen MB, Celniker SE, Rubin GM (2008) Tools for neuroanatomy and neurogenetics in Drosophila. Proc Natl Acad Sci U S A 105(28):9715–9720. https://doi.org/10.1073/pnas.0803697105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reim I, Frasch M, Schaub C (2017) Chapter six – T-box genes in Drosophila mesoderm development. In: Manfred F (ed) Current topics in developmental biology, vol 122. Academic, pp 161–193

    Google Scholar 

  • Sankar S, Yellajoshyula D, Zhang B, Teets B, Rockweiler N, Kroll KL (2016) Gene regulatory networks in neural cell fate acquisition from genome-wide chromatin association of Geminin and Zic1. Sci Rep 6:37412. https://doi.org/10.1038/srep37412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schaub C, Frasch M (2013) Org-1 is required for the diversification of circular visceral muscle founder cells and normal midgut morphogenesis. Dev Biol 376(2):245–259. https://doi.org/10.1016/j.ydbio.2013.01.022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schroeder MD, Greer C, Gaul U (2011) How to make stripes: deciphering the transition from non-periodic to periodic patterns in Drosophila segmentation. Development 138(14):3067–3078. https://doi.org/10.1242/dev.062141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sen A, Stultz BG, Lee H, Hursh DA (2010) Odd paired transcriptional activation of decapentaplegic in the Drosophila eye/antennal disc is cell autonomous but indirect. Dev Biol 343(1–2):167–177

    Article  CAS  PubMed  Google Scholar 

  • Stultz BG, Ray RP, Hursh DA (2005) Analysis of the shortvein cis-regulatory region of the decapentaplegic gene of Drosophila melanogaster. Genesis 42(3):181–192

    Article  CAS  PubMed  Google Scholar 

  • Stultz BG, Jackson DG, Mortin MA, Yang X, Beachy PA, Hursh DA (2006a) Transcriptional activation by extradenticle in the Drosophila visceral mesoderm. Dev Biol 290(2):482–494

    Article  CAS  PubMed  Google Scholar 

  • Stultz BG, Lee HJ, Ramon K, Hursh DA (2006b) Decapentaplegic head capsule mutations disrupt novel peripodial expression controlling the morphogenesis of the Drosophila ventral head. Dev Biol 296(2):329–339

    Article  CAS  PubMed  Google Scholar 

  • Stultz BG, Park SY, Mortin MA, Kennison JA, Hursh DA (2012) Hox proteins coordinate peripodial decapentaplegic expression to direct adult head morphogenesis in Drosophila. Dev Biol 369(2):362–376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Swantek D, Gergen JP (2004) Ftz modulates runt-dependent activation and repression of segment-polarity gene transcription. Development 131(10):2281–2290

    Article  CAS  PubMed  Google Scholar 

  • Tataroglu O, Emery P (2014) Studying circadian rhythms in Drosophila melanogaster. Methods 68(1):140–150. https://doi.org/10.1016/j.ymeth.2014.01.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tomancak P, Beaton A, Weiszmann R, Kwan E, Shu S, Lewis SE, Richards S, Ashburner M, Hartenstein V, Celniker SE, Rubin GM (2002) Systematic determination of patterns of gene expression during Drosophila embryogenesis. Genome Biol 3(12):RESEARCH0088

    Article  PubMed  PubMed Central  Google Scholar 

  • Tomancak P, Berman BP, Beaton A, Weiszmann R, Kwan E, Hartenstein V, Celniker SE, Rubin GM (2007) Global analysis of patterns of gene expression during Drosophila embryogenesis. Genome Biol 8(7):R145. https://doi.org/10.1186/gb-2007-8-7-r145

    Article  PubMed  PubMed Central  Google Scholar 

  • Winata CL, Kondrychyn I, Kumar V, Srinivasan KG, Orlov Y, Ravishankar A, Prabhakar S, Stanton LW, Korzh V, Mathavan S (2013) Genome wide analysis reveals Zic3 interaction with distal regulatory elements of stage specific developmental genes in zebrafish. PLoS Genet 9(10):e1003852. https://doi.org/10.1371/journal.pgen.1003852

    Article  PubMed  PubMed Central  Google Scholar 

  • Winata CL, Kondrychyn I, Korzh V (2015) Changing faces of transcriptional regulation reflected by Zic3. Curr Genomics 16(2):117–127. https://doi.org/10.2174/1389202916666150205124519

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang CP, Fu CC, Sugino K, Liu Z, Ren Q, Liu LY, Yao X, Lee LP, Lee T (2016) Transcriptomes of lineage-specific Drosophila neuroblasts profiled by genetic targeting and robotic sorting. Development 143(3):411–421. https://doi.org/10.1242/dev.129163

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zaffran S, Kuchler A, Lee HH, Frasch M (2001) biniou (FoxF), a central component in a regulatory network controlling visceral mesoderm development and midgut morphogenesis in Drosophila. Genes Dev 15(21):2900–2915

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

The authors would like to thank Dr. Heuijung Lee, who initiated the opa project in our lab, for her contributions to this review. We thank Drs. Annette Parks, Brent McCright, Malcolm Moos, and Mark Mortin for comments that improved the manuscript.

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  1. Division of Cell and Gene Therapy, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA

    Deborah A. Hursh & Brian G. Stultz

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Correspondence to Deborah A. Hursh .

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  1. Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Nagasaki, Japan

    Jun Aruga

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Hursh, D.A., Stultz, B.G. (2018). Odd-Paired: The Drosophila Zic Gene . In: Aruga, J. (eds) Zic family. Advances in Experimental Medicine and Biology, vol 1046. Springer, Singapore. https://doi.org/10.1007/978-981-10-7311-3_3

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