A Bow-Tie Genetic Architecture for Morphogenesis Suggested by a Genome-Wide RNAi Screen in

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During animal development, cellular morphogenesis plays a fundamental role in determining the shape and function of tissues and organs. Identifying the components that regulate and drive morphogenesis is thus a major goal of developmental biology. The four-celled tip of the Caenorhabditis elegans male tail is a simple but powerful model for studying the mechanism of morphogenesis and its spatiotemporal regulation. Here, through a genome-wide post-embryonic RNAi-feeding screen, we identified 212 components that regulate or participate in male tail tip morphogenesis. We constructed a working hypothesis for a gene regulatory network of tail tip morphogenesis. We found regulatory roles for the posterior Hox genes nob-1 and php-3, the TGF-β pathway, nuclear hormone receptors (e.g. nhr-25), the heterochronic gene blmp-1, and the GATA transcription factors egl-18 and elt-6. The majority of the pathways converge at dmd-3 and mab-3. In addition, nhr-25 and dmd-3/mab-3 regulate each others' expression, thus placing these three genes at the center of a complex regulatory network. We also show that dmd-3 and mab-3 negatively regulate other signaling pathways and affect downstream cellular processes such as vesicular trafficking (e.g. arl-1, rme-8) and rearrangement of the cytoskeleton (e.g. cdc-42, nmy-1, and nmy-2). Based on these data, we suggest that male tail tip morphogenesis is governed by a gene regulatory network with a bow-tie architecture.

Vyšlo v časopise: A Bow-Tie Genetic Architecture for Morphogenesis Suggested by a Genome-Wide RNAi Screen in. PLoS Genet 7(3): e32767. doi:10.1371/journal.pgen.1002010
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002010

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1. HadjantonakisKSolnica-KrezelL 2010 Developmental biology 50 years-investigating the emergence of shape. Introduction. Dev Biol 341 2 4

2. SulstonJEAlbertsonDGThomsonJN 1980 The Caenorhabditis elegans male: postembryonic development of nongonadal structures. Dev Biol 78 542 576

3. NguyenCQHallDHYangYFitchDH 1999 Morphogenesis of the Caenorhabditis elegans male tail tip. Dev Biol 207 86 106

4. SulstonJEHorvitzHR 1977 Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Dev Biol 56 110 156

5. ZhaoXYangYFitchDHHermanMA 2002 TLP-1 is an asymmetric cell fate determinant that responds to Wnt signals and controls male tail tip morphogenesis in C. elegans. Development 129 1497 1508

6. Del Rio-AlbrechtsenTKiontkeKChiouSYFitchDH 2006 Novel gain-of-function alleles demonstrate a role for the heterochronic gene lin-41 in C. elegans male tail tip morphogenesis. Dev Biol 297 74 86

7. MasonDARabinowitzJSPortmanDS 2008 dmd-3, a doublesex-related gene regulated by tra-1, governs sex-specific morphogenesis in C. elegans. Development 135 2373 2382

8. FitchDH 1997 Evolution of male tail development in rhabditid nematodes related to Caenorhabditis elegans. Syst Biol 46 145 179

9. SudhausWFitchD 2001 Comparative studies on the phylogeny and systematics of the rhabditidae (nematoda). J Nematol 33 1 70

10. HodgkinJ 2002 The remarkable ubiquity of DM domain factors as regulators of sexual phenotype: ancestry or aptitude? Genes Dev 16 2322 2326

11. RaymondCSShamuCEShenMMSeifertKJHirschB 1998 Evidence for evolutionary conservation of sex-determining genes. Nature 391 691 695

12. ShenMMHodgkinJ 1988 mab-3, a gene required for sex-specific yolk protein expression and a male-specific lineage in C. elegans. Cell 54 1019 1031

13. HodgkinJ 1987 A genetic analysis of the sex-determining gene, tra-1, in the nematode Caenorhabditis elegans. Genes Dev 1 731 745

14. ZarkowerDHodgkinJ 1992 Molecular analysis of the C. elegans sex-determining gene tra-1: a gene encoding two zinc finger proteins. Cell 70 237 249

15. MohlerWAShemerGdel CampoJJValansiCOpoku-SerebuohE 2002 The type I membrane protein EFF-1 is essential for developmental cell fusion. Dev Cell 2 355 362

16. ShemerGSuissaMKolotuevINguyenKCHallDH 2004 EFF-1 is sufficient to initiate and execute tissue-specific cell fusion in C. elegans. Curr Biol 14 1587 1591

17. KaoHLGunsalusKC 2008 Browsing multidimensional molecular networks with the generic network browser (N-Browse). Curr Protoc Bioinformatics Chapter 9 Unit 9 11

18. CseteMDoyleJ 2004 Bow ties, metabolism and disease. Trends Biotechnol 22 446 450

19. KitanoH 2004 Biological robustness. Nat Rev Genet 5 826 837

20. Rodriguez-CasoCCorominas-MurtraBSoleRV 2009 On the basic computational structure of gene regulatory networks. Mol Biosyst 5 1617 1629

21. ZhaoJYuHLuoJHCaoZWLiYX 2006 Hierarchical modularity of nested bow-ties in metabolic networks. BMC Bioinformatics 7 386

22. OdaKKitanoH 2006 A comprehensive map of the toll-like receptor signaling network. Mol Syst Biol 2 2006.0015

23. OdaKMatsuokaYFunahashiAKitanoH 2005 A comprehensive pathway map of epidermal growth factor receptor signaling. Mol Syst Biol 1 2005.0010

24. KrantzMAhmadpourDOttossonLGWarringerJWaltermannC 2009 Robustness and fragility in the yeast high osmolarity glycerol (HOG) signal-transduction pathway. Mol Syst Biol 5 281

25. LiCWChenBS 2010 Identifying functional mechanisms of gene and protein regulatory networks in response to a broader range of environmental stresses. Comp Funct Genomics 408705

26. KitanoHOdaK 2006 Robustness trade-offs and host-microbial symbiosis in the immune system. Mol Syst Biol 2 2006 0022

27. TieriPGrignolioAZaikinAMishtoMRemondiniD 2010 Network, degeneracy and bow tie integrating paradigms and architectures to grasp the complexity of the immune system. Theor Biol Med Model 7 32

28. FraserAGKamathRSZipperlenPMartinez-CamposMSohrmannM 2000 Functional genomic analysis of C. elegans chromosome I by systematic RNA interference. Nature 408 325 330

29. BerrizGFKingODBryantBSanderCRothFP 2003 Characterizing gene sets with FuncAssociate. Bioinformatics 19 2502 2504

30. MalloMWellikDMDeschampsJ 2010 Hox genes and regional patterning of the vertebrate body plan. Dev Biol 344 7 15

31. PearsonJCLemonsDMcGinnisW 2005 Modulating Hox gene functions during animal body patterning. Nat Rev Genet 6 893 904

32. HermanMAVassilievaLLHorvitzHRShawJEHermanRK 1995 The C. elegans gene lin-44, which controls the polarity of certain asymmetric cell divisions, encodes a Wnt protein and acts cell nonautonomously. Cell 83 101 110

33. KanekoHShimizuRYamamotoM 2010 GATA factor switching during erythroid differentiation. Curr Opin Hematol 17 163 168

34. HoICTaiTSPaiSY 2009 GATA3 and the T-cell lineage: essential functions before and after T-helper-2-cell differentiation. Nat Rev Immunol 9 125 135

35. ChouJProvotSWerbZ 2010 GATA3 in development and cancer differentiation: cells GATA have it! J Cell Physiol 222 42 49

36. KohKRothmanJH 2001 ELT-5 and ELT-6 are required continuously to regulate epidermal seam cell differentiation and cell fusion in C. elegans. Development 128 2867 2880

37. KohKPeyrotSMWoodCGWagmaisterJAMaduroMF 2002 Cell fates and fusion in the C. elegans vulval primordium are regulated by the EGL-18 and ELT-6 GATA factors — apparent direct targets of the LIN-39 Hox protein. Development 129 5171 5180

38. IkushimaHMiyazonoK 2010 TGFbeta signalling: a complex web in cancer progression. Nat Rev Cancer 10 415 424

39. GissendannerCRSluderAE 2000 nhr-25, the Caenorhabditis elegans ortholog of ftz-f1, is required for epidermal and somatic gonad development. Dev Biol 221 259 272

40. GuichetACopelandJWErdelyiMHlousekDZavorszkyP 1997 The nuclear receptor homologue Ftz-F1 and the homeodomain protein Ftz are mutually dependent cofactors. Nature 385 548 552

41. YuYLiWSuKYussaMHanW 1997 The nuclear hormone receptor Ftz-F1 is a cofactor for the Drosophila homeodomain protein Ftz. Nature 385 552 555

42. BroadusJMcCabeJREndrizziBThummelCSWoodardCT 1999 The Drosophila beta FTZ-F1 orphan nuclear receptor provides competence for stage-specific responses to the steroid hormone ecdysone. Mol Cell 3 143 149

43. AsahinaMIshiharaTJindraMKoharaYKatsuraI 2000 The conserved nuclear receptor Ftz-F1 is required for embryogenesis, moulting and reproduction in Caenorhabditis elegans. Genes Cells 5 711 723

44. DingXCSlackFJGrosshansH 2008 The let-7 microRNA interfaces extensively with the translation machinery to regulate cell differentiation. Cell Cycle 7 3083 3090

45. AgawaYSarhanMKageyamaYAkagiKTakaiM 2007 Drosophila Blimp-1 is a transient transcriptional repressor that controls timing of the ecdysone-induced developmental pathway. Mol Cell Biol 27 8739 8747

46. MartinsGCalameK 2008 Regulation and functions of Blimp-1 in T and B lymphocytes. Annu Rev Immunol 26 133 169

47. OhinataYPayerBO'CarrollDAncelinKOnoY 2005 Blimp1 is a critical determinant of the germ cell lineage in mice. Nature 436 207 213

48. VincentSDDunnNRSciammasRShapiro-ShalefMDavisMM 2005 The zinc finger transcriptional repressor Blimp1/Prdm1 is dispensable for early axis formation but is required for specification of primordial germ cells in the mouse. Development 132 1315 1325

49. NieKGomezMLandgrafPGarciaJFLiuY 2008 MicroRNA-mediated down-regulation of PRDM1/Blimp-1 in Hodgkin/Reed-Sternberg cells: a potential pathogenetic lesion in Hodgkin lymphomas. Am J Pathol 173 242 252

50. MatzukMM 2009 LIN28 lets BLIMP1 take the right course. Dev Cell 17 160 161

51. JonesDCandidoEP 2000 The NED-8 conjugating system in Caenorhabditis elegans is required for embryogenesis and terminal differentiation of the hypodermis. Dev Biol 226 152 165

52. ZhangYGrantBHirshD 2001 RME-8, a conserved J-domain protein, is required for endocytosis in Caenorhabditis elegans. Mol Biol Cell 12 2011 2021

53. ParcejDTampeR 2010 ABC proteins in antigen translocation and viral inhibition. Nat Chem Biol 6 572 580

54. LeeJIDhakalBKLeeJBandyopadhyayJJeongSY 2003 The Caenorhabditis elegans homologue of Down syndrome critical region 1, RCN-1, inhibits multiple functions of the phosphatase calcineurin. J Mol Biol 328 147 156

55. GoedertMBaurCPAhringerJJakesRHasegawaM 1996 PTL-1, a microtubule-associated protein with tau-like repeats from the nematode Caenorhabditis elegans. J Cell Sci 109 Pt 11 2661 2672

56. McDermottJBAamodtSAamodtE 1996 ptl-1, a Caenorhabditis elegans gene whose products are homologous to the tau microtubule-associated proteins. Biochemistry 35 9415 9423

57. HajduskovaMJindraMHermanMAAsahinaM 2009 The nuclear receptor NHR-25 cooperates with the Wnt/beta-catenin asymmetry pathway to control differentiation of the T seam cell in C. elegans. J Cell Sci 122 3051 3060

58. HayesGDFrandARRuvkunG 2006 The mir-84 and let-7 paralogous microRNA genes of Caenorhabditis elegans direct the cessation of molting via the conserved nuclear hormone receptors NHR-23 and NHR-25. Development 133 4631 4641

59. ChenZEastburnDJHanM 2004 The Caenorhabditis elegans nuclear receptor gene nhr-25 regulates epidermal cell development. Mol Cell Biol 24 7345 7358

60. SlackFJBassonMLiuZAmbrosVHorvitzHR 2000 The lin-41 RBCC gene acts in the C. elegans heterochronic pathway between the let-7 regulatory RNA and the LIN-29 transcription factor. Mol Cell 5 659 669

61. ShiASunLBanerjeeRTobinMZhangY 2009 Regulation of endosomal clathrin and retromer-mediated endosome to Golgi retrograde transport by the J-domain protein RME-8. EMBO J 28 3290 3302

62. FireAXuSMontgomeryMKKostasSADriverSE 1998 Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391 806 811

63. SimmerFTijstermanMParrishSKoushikaSPNonetML 2002 Loss of the putative RNA-directed RNA polymerase RRF-3 makes C. elegans hypersensitive to RNAi. Curr Biol 12 1317 1319

64. WhitacreJBenderA 2010 Degeneracy: a design principle for achieving robustness and evolvability. J Theor Biol 263 143 153

65. WagnerGPPavlicevMCheverudJM 2007 The road to modularity. Nat Rev Genet 8 921 931

66. HartwellLHHopfieldJJLeiblerSMurrayAW 1999 From molecular to modular cell biology. Nature 402 C47 52

67. GunsalusKCGeHSchetterAJGoldbergDSHanJD 2005 Predictive models of molecular machines involved in Caenorhabditis elegans early embryogenesis. Nature 436 861 865

68. PeterISDavidsonEH 2009 Modularity and design principles in the sea urchin embryo gene regulatory network. FEBS Lett 583 3948 3958

69. Van AukenKWeaverDCEdgarLGWoodWB 2000 Caenorhabditis elegans embryonic axial patterning requires two recently discovered posterior-group Hox genes. Proc Natl Acad Sci U S A 97 4499 4503

70. DonaldsonJGCasselDKahnRAKlausnerRD 1992 ADP-ribosylation factor, a small GTP-binding protein, is required for binding of the coatomer protein beta-COP to Golgi membranes. Proc Natl Acad Sci U S A 89 6408 6412

71. LiYKellyWGLogsdonJMJrSchurkoAMHarfeBD 2004 Functional genomic analysis of the ADP-ribosylation factor family of GTPases: phylogeny among diverse eukaryotes and function in C. elegans. FASEB J 18 1834 1850

72. WarnockDESchmidSL 1996 Dynamin GTPase, a force-generating molecular switch. Bioessays 18 885 893

73. UlrichFKriegMSchotzEMLinkVCastanonI 2005 Wnt11 functions in gastrulation by controlling cell cohesion through Rab5c and E-cadherin. Dev Cell 9 555 564

74. HammerschmidtMWedlichD 2008 Regulated adhesion as a driving force of gastrulation movements. Development 135 3625 3641

75. FujibayashiATaguchiTMisakiROhtaniMDohmaeN 2008 Human RME-8 is involved in membrane trafficking through early endosomes. Cell Struct Funct 33 35 50

76. GirardMPouponVBlondeauFMcPhersonPS 2005 The DnaJ-domain protein RME-8 functions in endosomal trafficking. J Biol Chem 280 40135 40143

77. KayAJHunterCP 2001 CDC-42 regulates PAR protein localization and function to control cellular and embryonic polarity in C. elegans. Curr Biol 11 474 481

78. NanceJPriessJR 2002 Cell polarity and gastrulation in C. elegans. Development 129 387 397

79. MartinAC 2010 Pulsation and stabilization: contractile forces that underlie morphogenesis. Dev Biol 341 114 125

80. BauerRLehmannCMartiniJEckardtFHochM 2004 Gap junction channel protein innexin 2 is essential for epithelial morphogenesis in the Drosophila embryo. Mol Biol Cell 15 2992 3004

81. LeitheESirnesSOmoriYRivedalE 2006 Downregulation of gap junctions in cancer cells. Crit Rev Oncog 12 225 256

82. StarichTSheehanMJadrichJShawJ 2001 Innexins in C. elegans. Cell Commun Adhes 8 311 314

83. KirschnerMGerhartJ 2005 Plausibility of life: great leaps of evolution. New Haven Yale University Press 331

84. GerhartJKirschnerM 1997 Cells, embryos and evolution: towards a cellular and developmental understanding of phenotypic variation and evolutionary adaptability. Malden, Massachusetts Blackwell Science 642

85. JordanJDIyengarR 1998 Modes of interactions between signaling pathways. Biochem Pharmacol 55 1347 1352

86. FreemanM 2000 Feedback control of intercellular signalling in development. Nature 408 313 319

87. CrewsSTPearsonJC 2009 Transcriptional autoregulation in development. Curr Biol 19 R241 246

88. AndersonJSalzerCLKumarJP 2006 Regulation of the retinal determination gene dachshund in the embryonic head and developing eye of Drosophila. Dev Biol 297 536 549

89. KumarJP 2001 Signalling pathways in Drosophila and vertebrate retinal development. Nat Rev Genet 2 846 857

90. MangoSE 2009 The molecular basis of organ formation: insights from the C. elegans foregut. Annu Rev Cell Dev Biol 25 597 628

91. GaudetJMangoSE 2002 Regulation of organogenesis by the Caenorhabditis elegans FoxA protein PHA-4. Science 295 821 825

92. ZhongMNiuWLuZJSarovMMurrayJI 2010 Genome-wide identification of binding sites defines distinct functions for Caenorhabditis elegans PHA-4/FOXA in development and environmental response. PLoS Genet 6 e1000848 doi:10.1371/journal.pgen.1000848

93. ConradM 1990 The geometry of evolution. Biosystems 24 61 81

94. GerhartJKirschnerM 2007 The theory of facilitated variation. Proc Natl Acad Sci U S A 104 Suppl 1 8582 8589

95. KirschnerMGerhartJ 1998 Evolvability. Proc Natl Acad Sci U S A 95 8420 8427

96. FitchDH 2000 Evolution of "rhabditidae" and the male tail. J Nematol 32 235 244

97. KiontkeKFitchDH 2005 The phylogenetic relationships of Caenorhabditis and other rhabditids. WormBook 1 11

98. BrennerS 1974 The genetics of Caenorhabditis elegans. Genetics 77 71 94

99. ZielJWHagedornEJAudhyaASherwoodDR 2009 UNC-6 (netrin) orients the invasive membrane of the anchor cell in C. elegans. Nat Cell Biol 11 183 189

100. ShevchukNABryksinAVNusinovichYACabelloFCSutherlandM 2004 Construction of long DNA molecules using long PCR-based fusion of several fragments simultaneously. Nucleic Acids Res 32 e19

101. ShanerNCCampbellRESteinbachPAGiepmansBNPalmerAE 2004 Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein. Nat Biotechnol 22 1567 1572