ttv

Summary

Gene Symbol: ttv
Description: tout-velu
Alias: CG10117, DEXT1, Dmel\CG10117, Ext1, P1.15, Ttv, dExt1, l(2)00681, l(2)05282, l(2)SH0631, l(2)SH2 0631, l(2)k00115, l(2)k03617, tout-velu, CG10117-PA, CG10117-PB, CG10117-PC, lethal (2) SH0631, tout velu, tout-velo, toutvelu, ttv-PA, ttv-PB, ttv-PC
Species: fruit fly
Products:     ttv

Top Publications

  1. Izumikawa T, Egusa N, Taniguchi F, Sugahara K, Kitagawa H. Heparan sulfate polymerization in Drosophila. J Biol Chem. 2006;281:1929-34 pubmed
    ..pathways in Drosophila has identified three genes, tout-velu (ttv), sister of tout-velu (sotv), and brother of toutvelu (botv), which encode homologues of human EXT1, EXT2, and EXTL3, respectively...
  2. Bellaiche Y, The I, Perrimon N. Tout-velu is a Drosophila homologue of the putative tumour suppressor EXT-1 and is needed for Hh diffusion. Nature. 1998;394:85-8 pubmed
    ..These results show the existence of a new conserved mechanism required for diffusion of Hedgehog. ..
  3. The I, Bellaiche Y, Perrimon N. Hedgehog movement is regulated through tout velu-dependent synthesis of a heparan sulfate proteoglycan. Mol Cell. 1999;4:633-9 pubmed
    ..Hh proteins undergo several modifications that tether them to the membrane. We have previously identified tout velu (ttv), a homolog of the mammalian EXT tumor suppressor gene family, as a gene required for movement of Hh...
  4. Ren Y, Kirkpatrick C, Rawson J, Sun M, Selleck S. Cell type-specific requirements for heparan sulfate biosynthesis at the Drosophila neuromuscular junction: effects on synapse function, membrane trafficking, and mitochondrial localization. J Neurosci. 2009;29:8539-50 pubmed publisher
    ..Our data support the emerging view that HSPG functions are not limited to the cell surface and matrix environments, but also affect a diverse set of cellular processes including membrane trafficking and organelle distributions. ..
  5. Toyoda H, Kinoshita Toyoda A, Fox B, Selleck S. Structural analysis of glycosaminoglycans in animals bearing mutations in sugarless, sulfateless, and tout-velu. Drosophila homologues of vertebrate genes encoding glycosaminoglycan biosynthetic enzymes. J Biol Chem. 2000;275:21856-61 pubmed
    ..These findings show that sugarless, sulfateless, and tout-velu affect glycosaminoglycan biosynthesis and demonstrate the utility of Drosophila as a model organism for studying the function and biosynthesis of glycosaminoglycans in vivo. ..
  6. Gorfinkiel N, Sierra J, Callejo A, Ibañez C, Guerrero I. The Drosophila ortholog of the human Wnt inhibitor factor Shifted controls the diffusion of lipid-modified Hedgehog. Dev Cell. 2005;8:241-53 pubmed
    ..We also show that human WIF inhibits Wg signaling in Drosophila without affecting the Hh pathway, indicating that different WIF family members might have divergent functions in each pathway. ..
  7. Baron M, Wong S, Nybakken K, Carey V, Madoff L. Host glycosaminoglycan confers susceptibility to bacterial infection in Drosophila melanogaster. Infect Immun. 2009;77:860-6 pubmed publisher
  8. Renault A, Ricardo S, Kunwar P, Santos A, Starz Gaiano M, Stein J, et al. Hedgehog does not guide migrating Drosophila germ cells. Dev Biol. 2009;328:355-62 pubmed publisher
    ..In contrast to previously reported findings and consistent with findings in zebrafish our data do not support the notion that Hh has a direct role in the guidance of migrating germ cells in flies. ..
  9. Takei Y, Ozawa Y, Sato M, Watanabe A, Tabata T. Three Drosophila EXT genes shape morphogen gradients through synthesis of heparan sulfate proteoglycans. Development. 2004;131:73-82 pubmed
    ..of two Drosophila genes, sister of tout-velu (sotv) and brother of tout-velu (botv), and new alleles of tout-velu (ttv)...

More Information

Publications72

  1. Nakato H, Kimata K. Heparan sulfate fine structure and specificity of proteoglycan functions. Biochim Biophys Acta. 2002;1573:312-8 pubmed
    ..In this review, we focus on the molecular basis of growth factor control by the sulfation status of heparan sulfate. ..
  2. Callejo A, Torroja C, Quijada L, Guerrero I. Hedgehog lipid modifications are required for Hedgehog stabilization in the extracellular matrix. Development. 2006;133:471-83 pubmed
    ..All these data show that the interaction of lipid-modified Hh with HSPG is important both for precise Hh spreading through the epithelium surface and for correct Hh reception. ..
  3. Glise B, Miller C, Crozatier M, Halbisen M, Wise S, Olson D, et al. Shifted, the Drosophila ortholog of Wnt inhibitory factor-1, controls the distribution and movement of Hedgehog. Dev Cell. 2005;8:255-66 pubmed
    ..Our data further indicate that Shf interacts with Hh and the heparan sulfate proteoglycans. Therefore, we propose that Shf stabilizes the interaction between Hh and the proteoglycans, an unexpected role for a member of the WIF-1 family. ..
  4. Gallet A, Rodriguez R, Ruel L, Therond P. Cholesterol modification of hedgehog is required for trafficking and movement, revealing an asymmetric cellular response to hedgehog. Dev Cell. 2003;4:191-204 pubmed
  5. Han C, Belenkaya T, Khodoun M, Tauchi M, Lin X, Lin X. Distinct and collaborative roles of Drosophila EXT family proteins in morphogen signalling and gradient formation. Development. 2004;131:1563-75 pubmed
    ..Previous studies in Drosophila demonstrated that tout-velu (ttv), the Drosophila EXT1, is required for Hh movement. However, the functions of other EXT family members are unknown...
  6. Yano H, Yamamoto Hino M, Abe M, Kuwahara R, Haraguchi S, Kusaka I, et al. Distinct functional units of the Golgi complex in Drosophila cells. Proc Natl Acad Sci U S A. 2005;102:13467-72 pubmed
    ..We propose that the different localizations among distinct Golgi units of molecules involved in glycosylation underlie the diversity of glycan modification. ..
  7. Moussian B, Tång E, Tonning A, Helms S, Schwarz H, NUSSLEIN VOLHARD C, et al. Drosophila Knickkopf and Retroactive are needed for epithelial tube growth and cuticle differentiation through their specific requirement for chitin filament organization. Development. 2006;133:163-71 pubmed
    ..We propose a model in which Knk and the predicted chitin-binding protein Rtv form membrane complexes essential for epithelial tubulogenesis and cuticle formation through their specific role in directing chitin filament assembly...
  8. Mezey J, Houle D, Nuzhdin S. Naturally segregating quantitative trait loci affecting wing shape of Drosophila melanogaster. Genetics. 2005;169:2101-13 pubmed
    ..Naturally segregating variation can therefore act through known signaling pathways to produce variation in vein position. ..
  9. Toyoda H, Kinoshita Toyoda A, Selleck S. Structural analysis of glycosaminoglycans in Drosophila and Caenorhabditis elegans and demonstration that tout-velu, a Drosophila gene related to EXT tumor suppressors, affects heparan sulfate in vivo. J Biol Chem. 2000;275:2269-75 pubmed
    ..The proteins encoded by the vertebrate tumor suppressor genes EXT1 and 2, show heparan sulfate co-polymerase activity, and it has been proposed that tout-velu affects Hedgehog ..
  10. Chanana B, Steigemann P, Jackle H, Vorbrüggen G. Reception of Slit requires only the chondroitin-sulphate-modified extracellular domain of Syndecan at the target cell surface. Proc Natl Acad Sci U S A. 2009;106:11984-8 pubmed publisher
    ..We propose that Dlp, which lacks CS modifications, participates in the transfer of Slit from its site of expression to the target cells, where CS-modified Sdc concentrates and presents the ligand. ..
  11. Mann R, Beachy P. Cholesterol modification of proteins. Biochim Biophys Acta. 2000;1529:188-202 pubmed
    ..Finally, the developmental consequences of chemical and genetic disruption of cholesterol homeostasis are summarized, along with the potential importance of cholesterol-rich lipid rafts in production of and response to the Hh signal. ..
  12. Cho J, Chak K, Andreone B, Wooley J, Kolodkin A. The extracellular matrix proteoglycan perlecan facilitates transmembrane semaphorin-mediated repulsive guidance. Genes Dev. 2012;26:2222-35 pubmed publisher
    ..Therefore, perlecan is required for Sema-1a-PlexA-mediated repulsive guidance, revealing roles for extracellular matrix proteoglycans in modulating transmembrane guidance cue signaling during neural development. ..
  13. Eugster C, Panàkovà D, Mahmoud A, Eaton S. Lipoprotein-heparan sulfate interactions in the Hh pathway. Dev Cell. 2007;13:57-71 pubmed
    ..They further suggest that the complement of proteins present on lipoprotein particles can regulate the activity of morphogens. ..
  14. Wilson I. Glycosylation of proteins in plants and invertebrates. Curr Opin Struct Biol. 2002;12:569-77 pubmed
    ..Whereas the forms of O-linked glycans in plants are unlike those in animals, studies on invertebrate O-glycosylation often yield information relevant to mammalian systems. ..
  15. Bischoff K, Ballew A, Simon M, O Reilly A. Wing defects in Drosophila xenicid mutant clones are caused by C-terminal deletion of additional sex combs (Asx). PLoS ONE. 2009;4:e8106 pubmed publisher
    ..Our results suggest that upregulation of Ubx transforms cells from a wing blade fate to a haltere fate, and that the presence of haltere cells within the wing blade is the primary defect leading to the adult wing phenotypes observed. ..
  16. Hayashi Y, Kobayashi S, Nakato H. Drosophila glypicans regulate the germline stem cell niche. J Cell Biol. 2009;187:473-80 pubmed publisher
    ..We propose that HSPGs define the physical space of the niche by serving as trans coreceptors, mediating short-range signaling by secreted factors. ..
  17. Fortini M, Skupski M, Boguski M, Hariharan I. A survey of human disease gene counterparts in the Drosophila genome. J Cell Biol. 2000;150:F23-30 pubmed
  18. Christian J. BMP, Wnt and Hedgehog signals: how far can they go?. Curr Opin Cell Biol. 2000;12:244-9 pubmed
    ..Furthermore, recent studies suggest that variations in the signaling range of these molecules may be due to tissue-specific differences in intracellular processing or tissue-restricted expression of binding proteins. ..
  19. Nusse R. Wnts and Hedgehogs: lipid-modified proteins and similarities in signaling mechanisms at the cell surface. Development. 2003;130:5297-305 pubmed
    ..Several other aspects of Wnt and Hedgehog transport and signaling are discussed, as well as the possible origin of these pathways. ..
  20. Dejima K, Kanai M, Akiyama T, Levings D, Nakato H. Novel contact-dependent bone morphogenetic protein (BMP) signaling mediated by heparan sulfate proteoglycans. J Biol Chem. 2011;286:17103-11 pubmed publisher
    ..Our findings provide the molecular foundation for novel contact-dependent signaling, which defines the physical space of the stem cell niche in vivo. ..
  21. Ingham P. Hedgehog signaling: a tale of two lipids. Science. 2001;294:1879-81 pubmed
    ..Recent studies suggest that the lipid adducts regulate the range and potency of the signals, whereas the sterol-sensing domain is essential for receptor activity. ..
  22. Capdevila J, Johnson R. Hedgehog signaling in vertebrate and invertebrate limb patterning. Cell Mol Life Sci. 2000;57:1682-94 pubmed
    ..Here we highlight the similarities and differences between the use of Hedgehog signaling in these two systems. ..
  23. Wang Z, Flax L, Kemp M, Linhardt R, Baron M. Host and pathogen glycosaminoglycan-binding proteins modulate antimicrobial peptide responses in Drosophila melanogaster. Infect Immun. 2011;79:606-16 pubmed publisher
  24. He B, Ludwig M, Dickerson D, Barse L, Arun B, Vilhjálmsson B, et al. Effect of genetic variation in a Drosophila model of diabetes-associated misfolded human proinsulin. Genetics. 2014;196:557-67 pubmed publisher
    ..RNAi against two additional genes in the heparan sulfate (HS) biosynthetic pathway (ttv and botv), in which sfl acts, also modified the eye phenotype in a hINS(C96Y)-dependent manner, strongly suggesting ..
  25. Deshpande G, Sethi N, Schedl P. toutvelu, a regulator of heparan sulfate proteoglycan biosynthesis, controls guidance cues for germ-cell migration. Genetics. 2007;176:905-12 pubmed
    ..Here, we demonstrate a novel role for toutvelu (ttv), a regulator of heparan sulfate proteoglycan biosynthesis during this process...
  26. Perrimon N, Bernfield M. Specificities of heparan sulphate proteoglycans in developmental processes. Nature. 2000;404:725-8 pubmed
  27. Dickson B, Dominguez M, van der Straten A, Hafen E. Control of Drosophila photoreceptor cell fates by phyllopod, a novel nuclear protein acting downstream of the Raf kinase. Cell. 1995;80:453-62 pubmed
    ..phyl thus represents a possible target gene of the Raf pathway during eye development, controlling the fates of a novel subset of photoreceptors. ..
  28. Kim B, Kitagawa H, Tamura Ji J, Kusche Gullberg M, Lindahl U, Sugahara K. Demonstration of a novel gene DEXT3 of Drosophila melanogaster as the essential N-acetylglucosamine transferase in the heparan sulfate biosynthesis: chain initiation and elongation. J Biol Chem. 2002;277:13659-65 pubmed
    ..These results suggest the essential roles of DEXT3, its human ortholog EXTL3, and the C. elegans ortholog rib-2 in the biosynthesis of heparan sulfate and heparin, if present, in the respective organisms. ..
  29. Baeg G, Perrimon N. Functional binding of secreted molecules to heparan sulfate proteoglycans in Drosophila. Curr Opin Cell Biol. 2000;12:575-80 pubmed
  30. Vincent J, Dubois L. Morphogen transport along epithelia, an integrated trafficking problem. Dev Cell. 2002;3:615-23 pubmed
    ..The question of how this is achieved has aroused the interest of many cell biologically minded developmental biologists. ..
  31. Eldar A, Barkai N. Interpreting clone-mediated perturbations of morphogen profiles. Dev Biol. 2005;278:203-7 pubmed
    ..Our results provide rigorous criteria to examine existing data and can facilitate the design and interpretation of future clone experiments. ..
  32. Tonning A, Helms S, Schwarz H, Uv A, Moussian B. Hormonal regulation of mummy is needed for apical extracellular matrix formation and epithelial morphogenesis in Drosophila. Development. 2006;133:331-41 pubmed
  33. Wendler F, Franch Marro X, Vincent J. How does cholesterol affect the way Hedgehog works?. Development. 2006;133:3055-61 pubmed
    ..However, the absence of the cholesterol adduct affects the spread of Hh within tissues. As we discuss here, the exact nature of this effect is controversial. ..
  34. Selleck S. Proteoglycans and pattern formation: sugar biochemistry meets developmental genetics. Trends Genet. 2000;16:206-12 pubmed
    ..In this review, these biological findings are placed in the context of proteoglycan biochemistry and molecular function. ..
  35. Lander A, Selleck S. The elusive functions of proteoglycans: in vivo veritas. J Cell Biol. 2000;148:227-32 pubmed
  36. Han C, Belenkaya T, Wang B, Lin X. Drosophila glypicans control the cell-to-cell movement of Hedgehog by a dynamin-independent process. Development. 2004;131:601-11 pubmed
    ..Previous studies in Drosophila have demonstrated that Tout-velu (Ttv), a heparan sulphate polymerase, is required for Hh movement across receiving cells...
  37. Amanai K, Jiang J. Distinct roles of Central missing and Dispatched in sending the Hedgehog signal. Development. 2001;128:5119-27 pubmed
    ..Finally, we show that cmn mutations bear molecular lesions in CG11495, which encodes a putative membrane bound acyltransferase related to Porcupine, a protein implicated in regulating the secretion of Wingless (Wg) signal. ..
  38. Levings D, Arashiro T, Nakato H. Heparan sulfate regulates the number and centrosome positioning of Drosophila male germline stem cells. Mol Biol Cell. 2016;27:888-96 pubmed publisher
    ..This study shows that specific HS modifications provide a novel regulatory mechanism for stem cell asymmetric division. The results also suggest that HS-mediated niche signaling acts upstream of GSC division orientation control. ..
  39. Park P, Reizes O, Bernfield M. Cell surface heparan sulfate proteoglycans: selective regulators of ligand-receptor encounters. J Biol Chem. 2000;275:29923-6 pubmed
  40. Sonnenfeld M, Barazesh N, Sedaghat Y, Fan C. The jing and ras1 pathways are functionally related during CNS midline and tracheal development. Mech Dev. 2004;121:1531-47 pubmed
    ..Egfr pathway genes and jing show dominant genetic interactions in the trachea and CNS midline. Together, these results show that jing regulates signal transduction in developing midline and tracheal cells. ..
  41. Bornemann D, Duncan J, Staatz W, Selleck S, Warrior R. Abrogation of heparan sulfate synthesis in Drosophila disrupts the Wingless, Hedgehog and Decapentaplegic signaling pathways. Development. 2004;131:1927-38 pubmed
    ..We have isolated mutations in sister of tout velu (sotv), a gene that encodes a co-polymerase that synthesizes HSPG glycosaminoglycan (GAG) chains...
  42. Briscoe J, Therond P. Hedgehog signaling: from the Drosophila cuticle to anti-cancer drugs. Dev Cell. 2005;8:143-51 pubmed
  43. Unckless R, Rottschaefer S, Lazzaro B. The complex contributions of genetics and nutrition to immunity in Drosophila melanogaster. PLoS Genet. 2015;11:e1005030 pubmed publisher
    ..Functional variation in these genes is segregating in a natural population, providing the substrate for evolutionary response to pathogen pressure in the context of nutritional environment. ..
  44. Murone M, Rosenthal A, de Sauvage F. Hedgehog signal transduction: from flies to vertebrates. Exp Cell Res. 1999;253:25-33 pubmed
    ..In the following review, we will not discuss in detail the role of Hh as a morphogen, but rather focus on its signal transduction pathway and its role in various human disorders. ..
  45. Chang W, Chang C, Chang Y, Sung H, Lin M, Chang S, et al. The Drosophila GOLPH3 homolog regulates the biosynthesis of heparan sulfate proteoglycans by modulating the retrograde trafficking of exostosins. Development. 2013;140:2798-807 pubmed publisher
    ..Mutations in the tumor suppressor genes EXT1 and EXT2 disturb HSPG biosynthesis and cause multiple osteochondroma (MO)...
  46. Chang Y, Wang Z, Flax L, Xu D, Esko J, Nizet V, et al. Glycosaminoglycan binding facilitates entry of a bacterial pathogen into central nervous systems. PLoS Pathog. 2011;7:e1002082 pubmed publisher
    ..Our results also highlight how the simpler yet genetically conserved Drosophila GAG pathways can provide a model organism to screen candidate molecules that can interrupt pathogen-GAG interactions for future therapeutic applications. ..
  47. Nishihara S. Glycosyltransferases and transporters that contribute to proteoglycan synthesis in Drosophila: Identification and functional analyses using the heritable and inducible RNAi system. Methods Enzymol. 2010;480:323-51 pubmed publisher
  48. Yao S, Lum L, Beachy P. The ihog cell-surface proteins bind Hedgehog and mediate pathway activation. Cell. 2006;125:343-57 pubmed
  49. Capdevila J, lzpisúa Belmonte J. Extracellular modulation of the Hedgehog, Wnt and TGF-beta signalling pathways during embryonic development. Curr Opin Genet Dev. 1999;9:427-33 pubmed
  50. Shaffer C, Stephens G, Thompson B, Funches L, Bernat J, Craig C, et al. Heterochromatin protein 2 (HP2), a partner of HP1 in Drosophila heterochromatin. Proc Natl Acad Sci U S A. 2002;99:14332-7 pubmed
    ..Mutations recovered in HP2 act as dominant suppressors of position effect variegation, confirming a role in heterochromatin spreading and gene silencing. ..
  51. Perrimon N, Hacker U. Wingless, hedgehog and heparan sulfate proteoglycans. Development. 2004;131:2509-11; author reply 2511-3 pubmed
  52. Ueyama M, Takemae H, Ohmae Y, Yoshida H, Toyoda H, Ueda R, et al. Functional analysis of proteoglycan galactosyltransferase II RNA interference mutant flies. J Biol Chem. 2008;283:6076-84 pubmed publisher
    ..These results demonstrated that dbeta3GalTII contributes to heparan sulfate proteoglycan synthesis in vitro and in vivo and also modulates Wingless distribution. ..
  53. Gurudatta B, Shashidhara L, Parnaik V. Lamin C and chromatin organization in Drosophila. J Genet. 2010;89:37-49 pubmed
    ..The lamC gene is situated in the fifth intron of the essential gene tout velu (ttv). We carried out genetic analysis of lamC during development...
  54. Chuang P, Kornberg T. On the range of hedgehog signaling. Curr Opin Genet Dev. 2000;10:515-22 pubmed
    ..Understanding how the movement of Hh is controlled and propelled will be key to understanding how it carries out its essential roles. ..
  55. Uchino R, Nonaka Y, Horigome T, Sugiyama S, Furukawa K. Loss of Drosophila A-type lamin C initially causes tendon abnormality including disintegration of cytoskeleton and nuclear lamina in muscular defects. Dev Biol. 2013;373:216-27 pubmed publisher
    ..Thus the critical function of A-type lamin C proteins in Drosophila musculature is to maintain proper function and morphology of tendon cells. ..
  56. McMahon A. More surprises in the Hedgehog signaling pathway. Cell. 2000;100:185-8 pubmed
  57. Deshpande G, Zhou K, Wan J, Friedrich J, Jourjine N, Smith D, et al. The hedgehog pathway gene shifted functions together with the hmgcr-dependent isoprenoid biosynthetic pathway to orchestrate germ cell migration. PLoS Genet. 2013;9:e1003720 pubmed publisher
    ..Finally, potentiation of Hh by hmgcr appears to depend upon cholesterol modification. ..
  58. Lum L, Beachy P. The Hedgehog response network: sensors, switches, and routers. Science. 2004;304:1755-9 pubmed
  59. Gallet A, Ruel L, Staccini Lavenant L, Therond P. Cholesterol modification is necessary for controlled planar long-range activity of Hedgehog in Drosophila epithelia. Development. 2006;133:407-18 pubmed
    ..We conclude that, as in vertebrates, cholesterol modification is essential for controlled long-range Hh signalling in Drosophila. ..
  60. Princivalle M, de Agostini A. Developmental roles of heparan sulfate proteoglycans: a comparative review in Drosophila, mouse and human. Int J Dev Biol. 2002;46:267-78 pubmed
  61. Kuwabara P, Labouesse M. The sterol-sensing domain: multiple families, a unique role?. Trends Genet. 2002;18:193-201 pubmed
    ..This article discusses how the SSD appears to function as a regulatory domain involved in linking vesicle trafficking and protein localization with such varied processes as cholesterol homeostasis, cell signalling and cytokinesis. ..
  62. Park Y, Rangel C, Reynolds M, Caldwell M, Johns M, Nayak M, et al. Drosophila perlecan modulates FGF and hedgehog signals to activate neural stem cell division. Dev Biol. 2003;253:247-57 pubmed
    ..Finally, analyses of mutations in trol, hh, and ttv suggest that Trol affects Hh movement...
  63. Dasgupta U, Dixit B, Rusch M, Selleck S, The I. Functional conservation of the human EXT1 tumor suppressor gene and its Drosophila homolog tout velu. Dev Genes Evol. 2007;217:555-61 pubmed
    ..In Drosophila, mutations in the tout velu (ttv) gene, a homolog of the mammalian EXT1 tumor suppressor gene, leads to abrogation of glycosaminoglycan (GAG)..