The Gyc76C Receptor Guanylyl Cyclase and the Foraging cGMP-Dependent Kinase Regulate Extracellular Matrix Organization and BMP Signaling in the Developing Wing of


Signaling between cells regulates many processes, including the choices cells make between different fates during development and regeneration, and misregulation of such signaling underlies many human pathologies. To understand how such signals control developmental decisions, it is necessary to elucidate both how cells regulate and respond to different levels of signaling, and how different types of signals combine and regulate each other. We have used genetic screening in the fruitfly Drosophila melanogaster to identify mutations that reduce or eliminate signals carried by Bone Morphogenetic Proteins (BMPs), and show that BMP signaling is sensitive Gyc76C, a peptide receptor that stimulates the production of cGMP in cells. We identify downstream intracellular effectors of this cGMP activity, but provide evidence that the effects on the BMP pathway are not mediated at the intracellular level, but rather through cGMP’s effects upon the extracellular matrix and matrix-remodeling proteinases, which in turn affects the activity of extracellular BMP-binding proteins. We discuss differences and parallels with other examples of cGMP activity in Drosophila melanogaster and mammals.


Vyšlo v časopise: The Gyc76C Receptor Guanylyl Cyclase and the Foraging cGMP-Dependent Kinase Regulate Extracellular Matrix Organization and BMP Signaling in the Developing Wing of. PLoS Genet 11(10): e32767. doi:10.1371/journal.pgen.1005576
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pgen.1005576

Souhrn

Signaling between cells regulates many processes, including the choices cells make between different fates during development and regeneration, and misregulation of such signaling underlies many human pathologies. To understand how such signals control developmental decisions, it is necessary to elucidate both how cells regulate and respond to different levels of signaling, and how different types of signals combine and regulate each other. We have used genetic screening in the fruitfly Drosophila melanogaster to identify mutations that reduce or eliminate signals carried by Bone Morphogenetic Proteins (BMPs), and show that BMP signaling is sensitive Gyc76C, a peptide receptor that stimulates the production of cGMP in cells. We identify downstream intracellular effectors of this cGMP activity, but provide evidence that the effects on the BMP pathway are not mediated at the intracellular level, but rather through cGMP’s effects upon the extracellular matrix and matrix-remodeling proteinases, which in turn affects the activity of extracellular BMP-binding proteins. We discuss differences and parallels with other examples of cGMP activity in Drosophila melanogaster and mammals.


Zdroje

1. Blair SS. Wing vein patterning in Drosophila and the analysis of intercellular signaling. Ann Rev Cell Dev Biol. 2007;23:293–319.

2. De Celis JF, Diaz-Benjumea FJ. Developmental basis for vein pattern variations in insect wings. Int J Dev Biol. 2003;47(7–8):653–63. 14756341

3. De Celis JF. Pattern formation in the Drosophila wing: The development of the veins. BioEssays: news and reviews in molecular, cellular and developmental biology. 2003;25(5):443–51.

4. Conley CA, Silburn R, Singer MA, Ralston A, Rohwer-Nutter D, Olson DJ, et al. Crossveinless 2 contains cysteine-rich domains and is required for high levels of BMP-like activity during the formation of the cross veins in Drosophila. Development. 2000;127(18):3947–59. 10952893

5. O'Connor MB, Umulis D, Othmer HG, Blair SS. Shaping BMP morphogen gradients in the Drosophila embryo and pupal wing. Development. 2006;133(2):183–93. 16368928

6. Umulis D, O'Connor MB, Blair SS. The extracellular regulation of bone morphogenetic protein signaling. Development. 2009;136(22):3715–28. doi: 10.1242/dev.031534 19855014

7. Ray RP, Wharton KA. Context-dependent relationships between the BMPs gbb and dpp during development of the Drosophila wing imaginal disk. Development. 2001;128(20):3913–25. 11641216

8. Ralston A, Blair SS. Long-range Dpp signaling is regulated to restrict BMP signaling to a crossvein competent zone. Developmental biology. 2005;280(1):187–200. 15766758

9. Matsuda S, Shimmi O. Directional transport and active retention of Dpp/BMP create wing vein patterns in Drosophila. Developmental biology. 2012;366(2):153–62. doi: 10.1016/j.ydbio.2012.04.009 22542596

10. Shimmi O, Ralston A, Blair SS, O'Connor MB. The crossveinless gene encodes a new member of the Twisted gastrulation family of BMP-binding proteins which, with Short gastrulation, promotes BMP signaling in the crossveins of the Drosophila wing. Developmental biology. 2005;282(1):70–83. 15936330

11. Vilmos P, Sousa-Neves R, Lukacsovich T, Marsh JL. crossveinless defines a new family of Twisted-gastrulation-like modulators of bone morphogenetic protein signalling. EMBO Rep. 2005;6(3):262–7. 15711536

12. Shimmi O, O'Connor MB. Physical properties of Tld, Sog, Tsg and Dpp protein interactions are predicted to help create a sharp boundary in Bmp signals during dorsoventral patterning of the Drosophila embryo. Development. 2003;130(19):4673–82. 12925593

13. Serpe M, Ralston A, Blair SS, O'Connor MB. Matching catalytic activity to developmental function: Tolloid-related processes Sog in order to help specify the posterior crossvein in the Drosophila wing. Development. 2005;132(11):2645–56. 15872004

14. Ambrosio AL, Taelman VF, Lee HX, Metzinger CA, Coffinier C, De Robertis EM. Crossveinless-2 Is a BMP feedback inhibitor that binds Chordin/BMP to regulate Xenopus embryonic patterning. Developmental cell. 2008;15(2):248–60. doi: 10.1016/j.devcel.2008.06.013 18694564

15. Serpe M, Umulis D, Ralston A, Chen J, Olson DJ, Avanesov A, et al. The BMP-binding protein Crossveinless 2 is a short-range, concentration-dependent, biphasic modulator of BMP signaling in Drosophila. Developmental cell. 2008;14(6):940–53. doi: 10.1016/j.devcel.2008.03.023 18539121

16. Zhang JL, Patterson LJ, Qiu LY, Graziussi D, Sebald W, Hammerschmidt M. Binding between Crossveinless-2 and Chordin von Willebrand factor type C domains promotes BMP signaling by blocking Chordin activity. PloS one. 2010;5(9):e12846. doi: 10.1371/journal.pone.0012846 20886103

17. Chen J, Honeyager SM, Schleede J, Avanesov A, Laughon A, Blair SS. Crossveinless d is a vitellogenin-like lipoprotein that binds BMPs and HSPGs, and is required for normal BMP signaling in the Drosophila wing. Development. 2012;139(12):2170–6. doi: 10.1242/dev.073817 22573617

18. Matsuda S, Blanco J, Shimmi O. A feed-forward loop coupling extracellular BMP transport and morphogenesis in Drosophila wing. PLoS genetics. 2013;9(3):e1003403. doi: 10.1371/journal.pgen.1003403 23555308

19. Waddington CH. The genetic control of wing development in Drosophila. J Genet. 1940;41:75–139.

20. Fristrom D, Wilcox M, Fristrom J. The distribution of PS integrins, laminin A and F-actin during key stages in Drosophila wing development. Development. 1993;117(2):509–23. 8330522

21. Fristrom D, Gotwals P, Eaton S, Kornberg TB, Sturtevant M, Bier E, et al. Blistered: a gene required for vein/intervein formation in wings of Drosophila. Development. 1994;120(9):2661–71. 7956840

22. Murray MA, Fessler LI, Palka J. Changing distributions of extracellular matrix components during early wing morphogenesis in Drosophila. Developmental biology. 1995;168(1):150–65. 7883070

23. Brabant MC, Fristrom D, Bunch TA, Brower DL. Distinct spatial and temporal functions for PS integrins during Drosophila wing morphogenesis. Development. 1996;122(10):3307–17. 8898242

24. Urbano JM, Torgler CN, Molnar C, Tepass U, Lopez-Varea A, Brown NH, et al. Drosophila laminins act as key regulators of basement membrane assembly and morphogenesis. Development. 2009;136(24):4165–76. doi: 10.1242/dev.044263 19906841

25. Wang X, Harris RE, Bayston LJ, Ashe HL. Type IV collagens regulate BMP signalling in Drosophila. Nature. 2008;455(7209):72–7. doi: 10.1038/nature07214 18701888

26. Bunt S, Hooley C, Hu N, Scahill C, Weavers H, Skaer H. Hemocyte-secreted type IV collagen enhances BMP signaling to guide renal tubule morphogenesis in Drosophila. Developmental cell. 2010;19(2):296–306. doi: 10.1016/j.devcel.2010.07.019 20708591

27. Sawala A, Sutcliffe C, Ashe HL. Multistep molecular mechanism for Bone morphogenetic protein extracellular transport in the Drosophila embryo. Proceedings of the National Academy of Sciences of the United States of America. 2012;109(28):11222–7. doi: 10.1073/pnas.1202781109 22733779

28. Winstanley J, Sawala A, Baldock C, Ashe HL. Synthetic enzyme-substrate tethering obviates the Tolloid-ECM interaction during BMP gradient formation. eLife. 2015;4.

29. Lindner JR, Hillman PR, Barrett AL, Jackson MC, Perry TL, Park Y, et al. The Drosophila Perlecan gene trol regulates multiple signaling pathways in different developmental contexts. BMC developmental biology. 2007;7:121. 17980035

30. Herranz H, Weng R, Cohen SM. Crosstalk between epithelial and mesenchymal tissues in tumorigenesis and imaginal disc development. Current biology: CB. 2014;24(13):1476–84. doi: 10.1016/j.cub.2014.05.043 24980505

31. Liu W, Yoon J, Burg M, Chen L, Pak WL. Molecular characterization of two Drosophila guanylate cyclases expressed in the nervous system. The Journal of biological chemistry. 1995;270(21):12418–27. 7759483

32. McNeil L, Chinkers M, Forte M. Identification, characterization, and developmental regulation of a receptor guanylyl cyclase expressed during early stages of Drosophila development. The Journal of biological chemistry. 1995;270(13):7189–96. 7706258

33. Morton DB, Hudson ML. Cyclic GMP regulation and function in insects. Adv Insect Physiol. 2002;29:1–54.

34. Ayoob JC, Yu HH, Terman JR, Kolodkin AL. The Drosophila receptor guanylyl cyclase Gyc76C is required for semaphorin-1a-plexin A-mediated axonal repulsion. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2004;24(30):6639–49.

35. Overend G, Cabrero P, Guo AX, Sebastian S, Cundall M, Armstrong H, et al. The receptor guanylate cyclase Gyc76C and a peptide ligand, NPLP1-VQQ, modulate the innate immune IMD pathway in response to salt stress. Peptides. 2012;34(1):209–18. doi: 10.1016/j.peptides.2011.08.019 21893139

36. Davies SA, Overend G, Sebastian S, Cundall M, Cabrero P, Dow JA, et al. Immune and stress response 'cross-talk' in the Drosophila Malpighian tubule. Journal of insect physiology. 2012;58(4):488–97. doi: 10.1016/j.jinsphys.2012.01.008 22306292

37. Patel U, Davies SA, Myat MM. Receptor-type guanylyl cyclase Gyc76C is required for development of the Drosophila embryonic somatic muscle. Biology open. 2012;1(6):507–15. doi: 10.1242/bio.2012943 23213443

38. Patel U, Myat MM. Receptor guanylyl cyclase Gyc76C is required for invagination, collective migration and lumen shape in the Drosophila embryonic salivary gland. Biology open. 2013;2(7):711–7. doi: 10.1242/bio.20134887 23862019

39. Chak K, Kolodkin AL. Function of the Drosophila receptor guanylyl cyclase Gyc76C in PlexA-mediated motor axon guidance. Development. 2014;141(1):136–47. doi: 10.1242/dev.095968 24284209

40. Potter LR. Guanylyl cyclase structure, function and regulation. Cellular signalling. 2011;23(12):1921–6. doi: 10.1016/j.cellsig.2011.09.001 21914472

41. Osborne KA, Robichon A, Burgess E, Butland S, Shaw RA, Coulthard A, et al. Natural behavior polymorphism due to a cGMP-dependent protein kinase of Drosophila. Science. 1997;277(5327):834–6. 9242616

42. Gurjar MV, Sharma RV, Bhalla RC. eNOS gene transfer inhibits smooth muscle cell migration and MMP-2 and MMP-9 activity. Arteriosclerosis, thrombosis, and vascular biology. 1999;19(12):2871–7. 10591663

43. Jurasz P, Sawicki G, Duszyk M, Sawicka J, Miranda C, Mayers I, et al. Matrix metalloproteinase 2 in tumor cell-induced platelet aggregation: regulation by nitric oxide. Cancer research. 2001;61(1):376–82. 11196190

44. Zaragoza C, Balbin M, Lopez-Otin C, Lamas S. Nitric oxide regulates matrix metalloprotease-13 expression and activity in endothelium. Kidney international. 2002;61(3):804–8. 11849429

45. Tsuruda T, Boerrigter G, Huntley BK, Noser JA, Cataliotti A, Costello-Boerrigter LC, et al. Brain natriuretic Peptide is produced in cardiac fibroblasts and induces matrix metalloproteinases. Circulation research. 2002;91(12):1127–34. 12480813

46. Vellaichamy E, Khurana ML, Fink J, Pandey KN. Involvement of the NF-kappa B/matrix metalloproteinase pathway in cardiac fibrosis of mice lacking guanylyl cyclase/natriuretic peptide receptor A. The Journal of biological chemistry. 2005;280(19):19230–42. 15710627

47. Krejci P, Masri B, Fontaine V, Mekikian PB, Weis M, Prats H, et al. Interaction of fibroblast growth factor and C-natriuretic peptide signaling in regulation of chondrocyte proliferation and extracellular matrix homeostasis. J Cell Sci. 2005;118(Pt 21):5089–100. 16234329

48. Li P, Oparil S, Novak L, Cao X, Shi W, Lucas J, et al. ANP signaling inhibits TGF-beta-induced Smad2 and Smad3 nuclear translocation and extracellular matrix expression in rat pulmonary arterial smooth muscle cells. Journal of applied physiology. 2007;102(1):390–8. 17038494

49. Li P, Wang D, Lucas J, Oparil S, Xing D, Cao X, et al. Atrial natriuretic peptide inhibits transforming growth factor beta-induced Smad signaling and myofibroblast transformation in mouse cardiac fibroblasts. Circulation research. 2008;102(2):185–92. 17991884

50. Schwappacher R, Weiske J, Heining E, Ezerski V, Marom B, Henis YI, et al. Novel crosstalk to BMP signalling: cGMP-dependent kinase I modulates BMP receptor and Smad activity. The EMBO journal. 2009;28(11):1537–50. doi: 10.1038/emboj.2009.103 19424179

51. Gong K, Xing D, Li P, Hilgers RH, Hage FG, Oparil S, et al. cGMP inhibits TGF-beta signaling by sequestering Smad3 with cytosolic beta2-tubulin in pulmonary artery smooth muscle cells. Molecular endocrinology. 2011;25(10):1794–803. doi: 10.1210/me.2011-1009 21868450

52. Schwappacher R, Kilic A, Kojonazarov B, Lang M, Diep T, Zhuang S, et al. A Molecular Mechanism for Therapeutic Effects of cGMP-elevating Agents in Pulmonary Arterial Hypertension. The Journal of biological chemistry. 2013;288(23):16557–66. doi: 10.1074/jbc.M113.458729 23612967

53. Golic KG. Site-specific recombination between homologous chromosomes in Drosophila. Science. 1991;252(5008):958–61. 2035025

54. Xu T, Rubin GM. Analysis of genetic mosaics in developing and adult Drosophila tissues. Development. 1993;117(4):1223–37. 8404527

55. Morata G, Ripoll P. Minutes: mutants of drosophila autonomously affecting cell division rate. Developmental biology. 1975;42(2):211–21. 1116643

56. Christoforou CP, Greer CE, Challoner BR, Charizanos D, Ray RP. The detached locus encodes Drosophila Dystrophin, which acts with other components of the Dystrophin Associated Protein Complex to influence intercellular signalling in developing wing veins. Developmental biology. 2008;313(2):519–32. 18093579

57. Cooper MT, Conant AW, Kennison JA. Molecular genetic analysis of Chd3 and polytene chromosome region 76B-D in Drosophila melanogaster. Genetics. 2010;185(3):811–22. doi: 10.1534/genetics.110.115121 20439780

58. Parks AL, Cook KR, Belvin M, Dompe NA, Fawcett R, Huppert K, et al. Systematic generation of high-resolution deletion coverage of the Drosophila melanogaster genome. Nat Genet. 2004;36(3):288–92. 14981519

59. Potter LR. Regulation and therapeutic targeting of peptide-activated receptor guanylyl cyclases. Pharmacology & therapeutics. 2011;130(1):71–82.

60. Hanks SK, Quinn AM, Hunter T. The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science. 1988;241(4861):42–52. 3291115

61. Klaiber M, Dankworth B, Kruse M, Hartmann M, Nikolaev VO, Yang RB, et al. A cardiac pathway of cyclic GMP-independent signaling of guanylyl cyclase A, the receptor for atrial natriuretic peptide. Proceedings of the National Academy of Sciences of the United States of America. 2011;108(45):18500–5. doi: 10.1073/pnas.1103300108 22027011

62. Thompson DK, Garbers DL. Dominant negative mutations of the guanylyl cyclase-A receptor. Extracellular domain deletion and catalytic domain point mutations. The Journal of biological chemistry. 1995;270(1):425–30. 7814405

63. Kalderon D, Rubin GM. cGMP-dependent protein kinase genes in Drosophila. The Journal of biological chemistry. 1989;264(18):10738–48. 2732245

64. Morrison DK, Murakami MS, Cleghon V. Protein kinases and phosphatases in the Drosophila genome. The Journal of cell biology. 2000;150(2):F57–62. 10908587

65. Tiong SY, Keizer C, Nash D, Bleskan J, Patterson D. Drosophila purine auxotrophy: new alleles of adenosine 2 exhibiting a complex visible phenotype. Biochem Genet. 1989;27(5–6):333–48. 2803228

66. Tiong SY, Nash D. Genetic analysis of the adenosine3 (Gart) region of the second chromosome of Drosophila melanogaster. Genetics. 1990;124(4):889–97. 2108904

67. Clark DV. Molecular and genetic analyses of Drosophila Prat, which encodes the first enzyme of de novo purine biosynthesis. Genetics. 1994;136(2):547–57. 8150282

68. O'Donnell AF, Tiong S, Nash D, Clark DV. The Drosophila melanogaster ade5 gene encodes a bifunctional enzyme for two steps in the de novo purine synthesis pathway. Genetics. 2000;154(3):1239–53. 10757766

69. Day JP, Dow JA, Houslay MD, Davies SA. Cyclic nucleotide phosphodiesterases in Drosophila melanogaster. Biochem J. 2005;388(Pt 1):333–42. 15673286

70. Day JP, Houslay MD, Davies SA. A novel role for a Drosophila homologue of cGMP-specific phosphodiesterase in the active transport of cGMP. Biochem J. 2006;393(Pt 2):481–8. 16232123

71. Day JP, Cleghon V, Houslay MD, Davies SA. Regulation of a Drosophila melanogaster cGMP-specific phosphodiesterase by prenylation and interaction with a prenyl-binding protein. Biochem J. 2008;414(3):363–74. doi: 10.1042/BJ20080560 18503409

72. Conti M, Beavo J. Biochemistry and physiology of cyclic nucleotide phosphodiesterases: essential components in cyclic nucleotide signaling. Annu Rev Biochem. 2007;76:481–511. 17376027

73. Arora K, Sinha C, Zhang W, Ren A, Moon CS, Yarlagadda S, et al. Compartmentalization of cyclic nucleotide signaling: a question of when, where, and why? Pflugers Arch. 2013;465(10):1397–407. doi: 10.1007/s00424-013-1280-6 23604972

74. Yu K, Sturtevant MA, Biehs B, Francois V, Padgett RW, Blackman RK, et al. The Drosophila decapentaplegic and short gastrulation genes function antagonistically during adult wing vein development. Development. 1996;122(12):4033–44. 9012523

75. Sotillos S, de Celis JF. Regulation of decapentaplegic expression during Drosophila wing veins pupal development. Mech Dev. 2006;123(3):241–51. 16423512

76. Molnar C, Lopez-Varea A, Hernandez R, de Celis JF. A gain-of-function screen identifying genes required for vein formation in the Drosophila melanogaster wing. Genetics. 2006;174(3):1635–59. 16980395

77. Friedrich MV, Schneider M, Timpl R, Baumgartner S. Perlecan domain V of Drosophila melanogaster. Sequence, recombinant analysis and tissue expression. European journal of biochemistry / FEBS. 2000;267(11):3149–59. 10824099

78. Egoz-Matia N, Nachman A, Halachmi N, Toder M, Klein Y, Salzberg A. Spatial regulation of cell adhesion in the Drosophila wing is mediated by Delilah, a potent activator of betaPS integrin expression. Developmental biology. 2011;351(1):99–109. doi: 10.1016/j.ydbio.2010.12.039 21215259

79. Whitelock JM, Murdoch AD, Iozzo RV, Underwood PA. The degradation of human endothelial cell-derived perlecan and release of bound basic fibroblast growth factor by stromelysin, collagenase, plasmin, and heparanases. The Journal of biological chemistry. 1996;271(17):10079–86. 8626565

80. Llano E, Pendas AM, Aza-Blanc P, Kornberg TB, Lopez-Otin C. Dm1-MMP, a matrix metalloproteinase from Drosophila with a potential role in extracellular matrix remodeling during neural development. The Journal of biological chemistry. 2000;275(46):35978–85. 10964925

81. Llano E, Adam G, Pendas AM, Quesada V, Sanchez LM, Santamaria I, et al. Structural and enzymatic characterization of Drosophila Dm2-MMP, a membrane-bound matrix metalloproteinase with tissue-specific expression. The Journal of biological chemistry. 2002;277(26):23321–9. 11967260

82. Page-McCaw A, Serano J, Sante JM, Rubin GM. Drosophila matrix metalloproteinases are required for tissue remodeling, but not embryonic development. Developmental cell. 2003;4(1):95–106. 12530966

83. Deady L, Shen W., Mosure S., Spradling A. C., Sun J. Matrix metalloproteinase 2 is required for ovulation and corpus luteum formation in Drosophila. PLoS genetics. 2015.

84. Uhlirova M, Bohmann D. JNK- and Fos-regulated Mmp1 expression cooperates with Ras to induce invasive tumors in Drosophila. Embo Journal. 2006;25(22):5294–304. 17082773

85. Brew K, Nagase H. The tissue inhibitors of metalloproteinases (TIMPs): an ancient family with structural and functional diversity. Biochimica et biophysica acta. 2010;1803(1):55–71. doi: 10.1016/j.bbamcr.2010.01.003 20080133

86. Wei S, Xie Z, Filenova E, Brew K. Drosophila TIMP is a potent inhibitor of MMPs and TACE: similarities in structure and function to TIMP-3. Biochemistry. 2003;42(42):12200–7. 14567681

87. Srivastava A, Pastor-Pareja JC, Igaki T, Pagliarini R, Xu T. Basement membrane remodeling is essential for Drosophila disc eversion and tumor invasion. Proceedings of the National Academy of Sciences of the United States of America. 2007;104(8):2721–6. 17301221

88. Pastor-Pareja JC, Xu T. Shaping cells and organs in Drosophila by opposing roles of fat body-secreted Collagen IV and perlecan. Developmental cell. 2011;21(2):245–56. doi: 10.1016/j.devcel.2011.06.026 21839919

89. Zang Y, Wan M, Liu M, Ke H, Ma S, Liu LP, et al. Plasma membrane overgrowth causes fibrotic collagen accumulation and immune activation in Drosophila adipocytes. eLife. 2015;4:e07187. doi: 10.7554/eLife.07187 26090908

90. Cho JY, Chak K, Andreone BJ, Wooley JR, Kolodkin AL. The extracellular matrix proteoglycan perlecan facilitates transmembrane semaphorin-mediated repulsive guidance. Genes & development. 2012;26(19):2222–35.

91. Ruka KA, Miller AP, Blumenthal EM. Inhibition of diuretic stimulation of an insect secretory epithelium by a cGMP-dependent protein kinase. American journal of physiology Renal physiology. 2013;304(9):F1210–6. doi: 10.1152/ajprenal.00231.2012 23445619

92. Zars T. Short-term memories in Drosophila are governed by general and specific genetic systems. Learning & memory. 2010;17(5):246–51.

93. Kanao T, Sawada T, Davies SA, Ichinose H, Hasegawa K, Takahashi R, et al. The Nitric Oxide-Cyclic GMP Pathway Regulates FoxO and Alters Dopaminergic Neuron Survival in Drosophila. PloS one. 2012;7(2).

94. Junger MA, Rintelen F, Stocker H, Wasserman JD, Vegh M, Radimerski T, et al. The Drosophila forkhead transcription factor FOXO mediates the reduction in cell number associated with reduced insulin signaling. Journal of biology. 2003;2(3):20. 12908874

95. Dolez M, Nicolas JF, Hirsinger E. Laminins, via heparan sulfate proteoglycans, participate in zebrafish myotome morphogenesis by modulating the pattern of Bmp responsiveness. Development. 2011;138(1):97–106. doi: 10.1242/dev.053975 21115608

96. Wang X, Page-McCaw A. A matrix metalloproteinase mediates long-distance attenuation of stem cell proliferation. The Journal of cell biology. 2014;206(7):923–36. doi: 10.1083/jcb.201403084 25267296

97. Zhang J, Schulze KL, Hiesinger PR, Suyama K, Wang S, Fish M, et al. Thirty-one flavors of Drosophila rab proteins. Genetics. 2007;176(2):1307–22. 17409086

98. Morin X, Daneman R, Zavortink M, Chia W. A protein trap strategy to detect GFP-tagged proteins expressed from their endogenous loci in Drosophila. Proceedings of the National Academy of Sciences of the United States of America. 2001;98(26):15050–5. 11742088

99. Zhai RG, Hiesinger PR, Koh TW, Verstreken P, Schulze KL, Cao Y, et al. Mapping Drosophila mutations with molecularly defined P element insertions. Proceedings of the National Academy of Sciences of the United States of America. 2003;100(19):10860–5. 12960394

100. Verleyen P, Baggerman G, Wiehart U, Schoeters E, Van Lommel A, De Loof A, et al. Expression of a novel neuropeptide, NVGTLARDFQLPIPNamide, in the larval and adult brain of Drosophila melanogaster. Journal of neurochemistry. 2004;88(2):311–9. 14690519

101. Tanaka T, Nakamura A. The endocytic pathway acts downstream of Oskar in Drosophila germ plasm assembly. Development. 2008;135(6):1107–17. doi: 10.1242/dev.017293 18272590

102. Satoh AK, O'Tousa JE, Ozaki K, Ready DF. Rab11 mediates post-Golgi trafficking of rhodopsin to the photosensitive apical membrane of Drosophila photoreceptors. Development. 2005;132(7):1487–97. 15728675

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2015 Číslo 10
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Eozinofilní granulomatóza s polyangiitidou
nový kurz

Betablokátory a Ca antagonisté z jiného úhlu
Autori: prof. MUDr. Michal Vrablík, Ph.D., MUDr. Petr Janský

Autori: doc. MUDr. Petr Čáp, Ph.D.

Farmakoterapie akutní a chronické bolesti

Získaná hemofilie - Povědomí o nemoci a její diagnostika

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Nemáte účet?  Registrujte sa

Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa