Piwi proteins and piRNAs step onto the systems biology stage

Advances in Experimental Medicine and Biology

Volumn 825, Issue , 2014, Pages 159-197

  Clark, Josef P ^a   Lau, Nelson C ^a  

^a BRANDEIS UNIVERSITY   (United States)

Author keywords

Germ cell development; Piwi pathway; Small regulatory RNA

Indexed keywords

ARGONAUTE PROTEIN; PIWI INTERACTING RNA; PIWI PROTEIN; PIWIL1 PROTEIN, HUMAN; SMALL INTERFERING RNA; TRANSCRIPTOME;

ARTICLE; BIOGENESIS; CAENORHABDITIS ELEGANS; CHROMATIN STRUCTURE; GENE CONTROL; GENE FUNCTION; GENE SILENCING; GERM CELL; INTRACELLULAR SIGNALING; MOLECULAR EVOLUTION; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN LOCALIZATION; RNA INTERFERENCE; SPECIES DIFFERENCE; SPECIES DIVERSITY; SYSTEMS BIOLOGY; TRANSCRIPTIONAL GENE SILENCING; ANIMAL; GENETICS; HUMAN; HUMAN GENOME; METABOLISM; PHYSIOLOGY; TOTIPOTENT STEM CELL;

ANIMALIA; INVERTEBRATA; VERTEBRATA;

ANIMALS; ARGONAUTE PROTEINS; GENOME, HUMAN; GERM CELLS; HUMANS; RNA, SMALL INTERFERING; SYSTEMS BIOLOGY; TOTIPOTENT STEM CELLS; TRANSCRIPTOME;

EID: 84926613099     PISSN: 00652598     EISSN: 22148019     Source Type: Book Series    
DOI: 10.1007/978-1-4939-1221-6_5     Document Type: Article

References (206)

1. Ambros V (2011) MicroRNAs and developmental timing. Curr Opin Genet Dev 21:511-517
2. Anand A, Kai T (2012) The tudor domain protein kumo is required to assemble the nuage and to generate germline piRNAs in Drosophila. EMBO J 31:870-882
3. Aravin AA, Sachidanandam R, Bourc'his D, Schaefer C, Pezic D, Toth KF, Bestor T, Hannon GJ (2008) A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice. Mol Cell 31:785-799
4. Aravin AA, Sachidanandam R, Girard A, Fejes-Toth K, Hannon GJ (2007) Developmentally regulated piRNA clusters implicate MILI in transposon control. Science 316:744-747
5. Aravin AA, van der Heijden GW, Castaneda J, Vagin VV, Hannon GJ, Bortvin A (2009) Cytoplasmic compartmentalization of the fetal piRNA pathway in mice. PLoS Genet 5:e1000764
6. Armisen J, Gilchrist MJ, Wilczynska A, Standart N, Miska EA (2009) Abundant and dynamically expressed miRNAs, piRNAs, and other small RNAs in the vertebrate Xenopus tropicalis. Genome Res 19:1766-1775
7. Ashe A, Sapetschnig A, Weick EM, Mitchell J, Bagijn MP, Cording AC, Doebley AL, Goldstein LD, Lehrbach NJ, Le Pen J et al (2012) piRNAs can trigger a multigenerational epigenetic memory in the germline of C. elegans. Cell 150:88-99
8. Bagijn MP, Goldstein LD, Sapetschnig A, Weick EM, Bouasker S, Lehrbach NJ, Simard MJ, Miska EA (2012) Function, targets, and evolution of Caenorhabditis elegans piRNAs. Science 337:574-578
9. Bailey CH, Kandel ER, Si K (2004) The persistence of long-term memory: a molecular approach to self-sustaining changes in learning-induced synaptic growth. Neuron 44:49-57
10. Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136:215-233
11. Batista PJ, Ruby JG, Claycomb JM, Chiang R, Fahlgren N, Kasschau KD, Chaves DA, Gu W, Vasale JJ, Duan S et al (2008) PRG-1 and 21U-RNAs interact to form the piRNA complex required for fertility in C. elegans. Mol Cell 31:67-78
12. Becalska AN, Kim YR, Belletier NG, Lerit DA, Sinsimer KS, Gavis ER (2011) Aubergine is a component of a nanos mRNA localization complex. Dev Biol 349:46-52
13. Betel D, Sheridan R, Marks DS, Sander C (2007) Computational analysis of mouse piRNA sequence and biogenesis. PLoS Comput Biol 3:e222
14. Beyret E, Liu N, Lin H (2012) piRNA biogenesis during adult spermatogenesis in mice is independent of the ping-pong mechanism. Cell Res 22:1429-1439
15. Billi AC, Alessi AF, Khivansara V, Han T, Freeberg M, Mitani S, Kim JK (2012) The Caenorhabditis elegans HEN1 ortholog, HENN-1, methylates and stabilizes select subclasses of germline small RNAs. PLoS Genet 8:e1002617
16. Brennecke J, Aravin AA, Stark A, Dus M, Kellis M, Sachidanandam R, Hannon GJ (2007) Discrete small RNA-generating loci as master regulators of transposon activity in Drosophila. Cell 128:1089-1103
17. Brennecke J, Malone CD, Aravin AA, Sachidanandam R, Stark A, Hannon GJ (2008) An epigenetic role for maternally inherited piRNAs in transposon silencing. Science 322:1387-1392
18. Brower-Toland B, Findley SD, Jiang L, Liu L, Yin H, Dus M, Zhou P, Elgin SC, Lin H (2007) Drosophila PIWI associates with chromatin and interacts directly with HP1a. Genes Dev 21:2300-2311
19. Buckley BA, Burkhart KB, Gu SG, Spracklin G, Kershner A, Fritz H, Kimble J, Fire A, Kennedy S (2012) A nuclear Argonaute promotes multigenerational epigenetic inheritance and germline immortality. Nature 489:447-451
20. Carmell MA, Girard A, van de Kant HJ, Bourc'his D, Bestor TH, de Rooij DG, Hannon GJ (2007) MIWI2 is essential for spermatogenesis and repression of transposons in the mouse male germline. Dev Cell 12(4):503-514
21. Carthew RW, Sontheimer EJ (2009) Origins and mechanisms of miRNAs and siRNAs. Cell 136:642-655
22. Castillo DM, Mell JC, Box KS, Blumenstiel JP (2011) Molecular evolution under increasing transposable element burden in Drosophila: a speed limit on the evolutionary arms race. BMC Evol Biol 11:258
23. Cecere G, Zheng GX, Mansisidor AR, Klymko KE, Grishok A (2012) Promoters recognized by forkhead proteins exist for individual 21U-RNAs. Mol Cell 47:734-745
24. Cheloufi S, Dos Santos CO, Chong MM, Hannon GJ (2010) A dicer-independent miRNA biogenesis pathway that requires Ago catalysis. Nature 465:584-589
25. Chen C, Jin J, James DA, Adams-Cioaba MA, Park JG, Guo Y, Tenaglia E, Xu C, Gish G, Min J et al (2009) Mouse Piwi interactome identifies binding mechanism of Tdrkh Tudor domain to arginine methylated Miwi. Proc Natl Acad Sci U S A 106:20336-20341
26. Chuma S, Hosokawa M, Kitamura K, Kasai S, Fujioka M, Hiyoshi M, Takamune K, Noce T, Nakatsuji N (2006) Tdrd1/Mtr-1, a tudor-related gene, is essential for male germ-cell differentiation and nuage/germinal granule formation in mice. Proc Natl Acad Sci U S A 103:15894-15899
27. Cifuentes D, Xue H, Taylor DW, Patnode H, Mishima Y, Cheloufi S, Ma E, Mane S, Hannon GJ, Lawson ND et al (2010) A novel miRNA processing pathway independent of Dicer requires Argonaute2 catalytic activity. Science 328:1694-1698
28. Claycomb JM (2012) Caenorhabditis elegans small RNA pathways make their mark on chromatin. DNA Cell Biol 31(Suppl 1):S17-33
29. Claycomb JM, Batista PJ, Pang KM, Gu W, Vasale JJ, van Wolfswinkel JC, Chaves DA, Shirayama M, Mitani S, Ketting RF et al (2009) The Argonaute CSR-1 and its 22G-RNA cofactors are required for holocentric chromosome segregation. Cell 139:123-134
30. Conine CC, Batista PJ, Gu W, Claycomb JM, Chaves DA, Shirayama M, Mello CC (2010) Argonautes ALG-3 and ALG-4 are required for spermatogenesis-specific 26G-RNAs and thermotolerant sperm in Caenorhabditis elegans. Proc Natl Acad Sci U S A 107:3588-3593
31. Couvillion MT, Sachidanandam R, Collins K (2010) A growth-essential Tetrahymena Piwi protein carries tRNA fragment cargo. Genes Dev 24:2742-2747
32. Cox DN, Chao A, Baker J, Chang L, Qiao D, Lin H (1998) A novel class of evolutionarily conserved genes defined by piwi are essential for stem cell self-renewal. Genes Dev 12:3715-3727
33. Cox DN, Chao A, Lin H (2000) piwi encodes a nucleoplasmic factor whose activity modulates the number and division rate of germline stem cells. Development 127:503-514
34. Czech B, Preall JB, McGinn J, Hannon GJ (2013) A transcriptome-wide RNAi screen in the Drosophila ovary reveals factors of the germline piRNA pathway. Mol Cell 50(5):749-761
35. Darricarrere N, Liu N, Watanabe T, Lin H (2013) Function of Piwi, a nuclear Piwi/Argonaute protein, is independent of its slicer activity. Proc Natl Acad Sci U S A 110:1297-1302
36. Das PP, Bagijn MP, Goldstein LD, Woolford JR, Lehrbach NJ, Sapetschnig A, Buhecha HR, Gilchrist MJ, Howe KL, Stark R et al (2008) Piwi and piRNAs act upstream of an endogenous siRNA pathway to suppress Tc3 transposon mobility in the Caenorhabditis elegans germline. Mol Cell 31:79-90
37. De Fazio S, Bartonicek N, Di Giacomo M, Abreu-Goodger C, Sankar A, Funaya C, Antony C, Moreira PN, Enright AJ, O'Carroll D (2011) The endonuclease activity of Mili fuels piRNA amplification that silences LINE1 elements. Nature 480:259-263
38. de Vanssay A, Bouge AL, Boivin A, Hermant C, Teysset L, Delmarre V, Antoniewski C, Ronsseray S (2012) Paramutation in Drosophila linked to emergence of a piRNA-producing locus. Nature 490:112-115
39. Deng W, Lin H (2002) miwi, a murine homolog of piwi, encodes a cytoplasmic protein essential for spermatogenesis. Dev Cell 2:819-830
40. Di Giacomo M, Comazzetto S, Saini H, De Fazio S, Carrieri C, Morgan M, Vasiliauskaite L, Benes V, Enright AJ, O'Carroll D (2013) Multiple epigenetic mechanisms and the piRNA pathway enforce LINE1 silencing during adult spermatogenesis. Mol Cell 50:601-608
41. Donertas D, Sienski G, Brennecke J (2013) Drosophila Gtsf1 is an essential component of the Piwi-mediated transcriptional silencing complex. Genes Dev 27:1693-1705
42. Fang W, Wang X, Bracht JR, Nowacki M, Landweber LF (2012) Piwi-interacting RNAs protect DNA against loss during Oxytricha genome rearrangement. Cell 151:1243-1255
43. Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391:806-811
44. Fischer SE (2010) Small RNA-mediated gene silencing pathways in C. elegans. Int J Biochem Cell Biol 42:1306-1315
45. Frost RJ, Hamra FK, Richardson JA, Qi X, Bassel-Duby R, Olson EN (2010) MOV10L1 is necessary for protection of spermatocytes against retrotransposons by Piwi-interacting RNAs. Proc Natl Acad Sci U S A 107:11847-11852
46. Gangaraju VK, Yin H, Weiner MM, Wang J, Huang XA, Lin H (2011) Drosophila Piwi functions in Hsp90-mediated suppression of phenotypic variation. Nat Genet 43:153-158
47. Gent JI, Lamm AT, Pavelec DM, Maniar JM, Parameswaran P, Tao L, Kennedy S, Fire AZ (2010) Distinct phases of siRNA synthesis in an endogenous RNAi pathway in C. elegans soma. Mol Cell 37:679-689
48. Ghildiyal M, Seitz H, Horwich MD, Li C, Du T, Lee S, Xu J, Kittler EL, Zapp ML, Weng Z et al (2008) Endogenous siRNAs derived from transposons and mRNAs in Drosophila somatic cells. Science 320:1077-1081
49. Ghildiyal M, Zamore PD (2009) Small silencing RNAs: an expanding universe. Nat Rev Genet 10:94-108
50. Goic B, Vodovar N, Mondotte JA, Monot C, Frangeul L, Blanc H, Gausson V, Vera-Otarola J, Cristofari G, Saleh MC (2013) RNA-mediated interference and reverse transcription control the persistence of RNA viruses in the insect model Drosophila. Nat Immunol 14:396-403
51. Grentzinger T, Armenise C, Brun C, Mugat B, Serrano V, Pelisson A, Chambeyron S (2012) piRNAmediated transgenerational inheritance of an acquired trait. Genome Res 22:1877-1888
52. Grimaud C, Bantignies F, Pal-Bhadra M, Ghana P, Bhadra U, Cavalli G (2006) RNAi components are required for nuclear clustering of Polycomb group response elements. Cell 124:957-971
53. Grimson A, Srivastava M, Fahey B, Woodcroft BJ, Chiang HR, King N, Degnan BM, Rokhsar DS, Bartel DP (2008) Early origins and evolution of microRNAs and Piwi-interacting RNAs in animals. Nature 455:1193-1197
54. Grivna ST, Pyhtila B, Lin H (2006) MIWI associates with translational machinery and PIWIinteracting RNAs (piRNAs) in regulating spermatogenesis. Proc Natl Acad Sci U S A 103:13415-13420
55. Gu W, Lee HC, Chaves D, Youngman EM, Pazour GJ, Conte D Jr, Mello CC (2012) CapSeq and CIP-TAP identify Pol II start sites and reveal capped small RNAs as C. elegans piRNA precursors. Cell 151:1488-1500
56. Gu W, Shirayama M, Conte D Jr, Vasale J, Batista PJ, Claycomb JM, Moresco JJ, Youngman EM, Keys J, Stoltz MJ et al (2009) Distinct argonaute-mediated 22G-RNA pathways direct genome surveillance in the C. elegans germline. Mol Cell 36:231-244
57. Guang S, Bochner AF, Burkhart KB, Burton N, Pavelec DM, Kennedy S (2010) Small regulatory RNAs inhibit RNA polymerase II during the elongation phase of transcription. Nature 465:1097-1101
58. Gunawardane LS, Saito K, Nishida KM, Miyoshi K, Kawamura Y, Nagami T, Siomi H, Siomi MC (2007) A slicer-mediated mechanism for repeat-associated siRNA 5′ end formation in Drosophila. Science 315:1587-1590
59. Haase AD, Fenoglio S, Muerdter F, Guzzardo PM, Czech B, Pappin DJ, Chen C, Gordon A, Hannon GJ (2010) Probing the initiation and effector phases of the somatic piRNA pathway in Drosophila. Genes Dev 24:2499-2504
60. Hall SE, Chirn GW, Lau NC, Sengupta P (2013) RNAi pathways contribute to developmental history-dependent phenotypic plasticity in C. elegans. RNA 19(3):306-319
61. Han T, Manoharan AP, Harkins TT, Bouffard P, Fitzpatrick C, Chu DS, Thierry-Mieg D, Thierry-Mieg J, Kim JK (2009) 26G endo-siRNAs regulate spermatogenic and zygotic gene expression in Caenorhabditis elegans. Proc Natl Acad Sci U S A 106:18674-18679
62. Handler D, Meixner K, Pizka M, Lauss K, Schmied C, Gruber FS, Brennecke J (2013) The genetic makeup of the Drosophila piRNA pathway. Mol Cell 50(5):762-777
63. Handler D, Olivieri D, Novatchkova M, Gruber FS, Meixner K, Mechtler K, Stark A, Sachidanandam R, Brennecke J (2011) A systematic analysis of Drosophila TUDOR domain-containing proteins identifies Vreteno and the Tdrd12 family as essential primary piRNA pathway factors. EMBO J 30:3977-3993
64. Harris AN, Macdonald PM (2001) Aubergine encodes a Drosophila polar granule component required for pole cell formation and related to eIF2C. Development 128:2823-2832
65. Haynes KA, Caudy AA, Collins L, Elgin SC (2006) Element 1360 and RNAi components contribute to HP1-dependent silencing of a pericentric reporter. Curr Biol 16:2222-2227
66. Horwich MD, Li C, Matranga C, Vagin V, Farley G, Wang P, Zamore PD (2007) The Drosophila RNA methyltransferase, DmHen1, modifies germline piRNAs and single-stranded siRNAs in RISC. Curr Biol 17:1265-1272
67. Hou Y, Yuan J, Zhou X, Fu X, Cheng H, Zhou R (2012) DNA demethylation and USF regulate the meiosis-specific expression of the mouse Miwi. PLoS Genet 8:e1002716
68. Houston DW, King ML (2000) Germ plasm and molecular determinants of germ cell fate. Curr Top Dev Biol 50:155-181
69. Houwing S, Berezikov E, Ketting RF (2008) Zili is required for germ cell differentiation and meiosis in zebrafish. EMBO J 27:2702-2711
70. Houwing S, Kamminga LM, Berezikov E, Cronembold D, Girard A, van den Elst H, Filippov DV, Blaser H, Raz E, Moens CB et al (2007) A role for Piwi and piRNAs in germ cell maintenance and transposon silencing in Zebrafish. Cell 129:69-82
71. Huang H, Gao Q, Peng X, Choi SY, Sarma K, Ren H, Morris AJ, Frohman MA (2011a) piRNAassociated germline nuage formation and spermatogenesis require MitoPLD profusogenic mitochondrial-surface lipid signaling. Dev Cell 20:376-387
72. Huang HY, Houwing S, Kaaij LJ, Meppelink A, Redl S, Gauci S, Vos H, Draper BW, Moens CB, Burgering BM et al (2011b) Tdrd1 acts as a molecular scaffold for Piwi proteins and piRNA targets in zebrafish. EMBO J 30:3298-3308
73. Huang XA, Yin H, Sweeney S, Raha D, Snyder M, Lin H (2013) A major epigenetic programming mechanism guided by piRNAs. Dev Cell 24:502-516
74. Ipsaro JJ, Haase AD, Knott SR, Joshua-Tor L, Hannon GJ (2012) The structural biochemistry of Zucchini implicates it as a nuclease in piRNA biogenesis. Nature 491:279-283
75. Irvine DV, Zaratiegui M, Tolia NH, Goto DB, Chitwood DH, Vaughn MW, Joshua-Tor L, Martienssen RA (2006) Argonaute slicing is required for heterochromatic silencing and spreading. Science 313:1134-1137
76. Ishizu H, Siomi H, Siomi MC (2012) Biology of PIWI-interacting RNAs: new insights into biogenesis and function inside and outside of germlines. Genes Dev 26:2361-2373
77. Janic A, Mendizabal L, Llamazares S, Rossell D, Gonzalez C (2010) Ectopic expression of germline genes drives malignant brain tumor growth in Drosophila. Science 330:1824-1827
78. Juliano C, Wang J, Lin H (2011) Uniting germline and stem cells: the function of Piwi proteins and the piRNA pathway in diverse organisms. Annu Rev Genet 45:447-469
79. Kamminga LM, van Wolfswinkel JC, Luteijn MJ, Kaaij LJ, Bagijn MP, Sapetschnig A, Miska EA, Berezikov E, Ketting RF (2012) Differential impact of the HEN1 homolog HENN-1 on 21U and 26G RNAs in the germline of Caenorhabditis elegans. PLoS Genet 8:e1002702
80. Kawaoka S, Izumi N, Katsuma S, Tomari Y (2011) 3′ end formation of PIWI-interacting RNAs in vitro. Mol Cell 43:1015-1022
81. Kawaoka S, Mitsutake H, Kiuchi T, Kobayashi M, Yoshikawa M, Suzuki Y, Sugano S, Shimada T, Kobayashi J, Tomari Y et al (2012) A role for transcription from a piRNA cluster in de novo piRNA production. RNA 18:265-273
82. Kelleher ES, Edelman NB, Barbash DA (2012) Drosophila interspecific hybrids phenocopy piRNA-pathway mutants. PLoS Biol 10:e1001428
83. Ketting RF (2011) The many faces of RNAi. Dev Cell 20:148-161
84. Khurana JS, Wang J, Xu J, Koppetsch BS, Thomson TC, Nowosielska A, Li C, Zamore PD, Weng Z, Theurkauf WE (2011) Adaptation to P element transposon invasion in Drosophila melanogaster. Cell 147:1551-1563
85. Kirino Y, Kim N, de Planell-Saguer M, Khandros E, Chiorean S, Klein PS, Rigoutsos I, Jongens TA, Mourelatos Z (2009) Arginine methylation of Piwi proteins catalysed by dPRMT5 is required for Ago3 and Aub stability. Nat Cell Biol 11:652-658
86. Klattenhoff C, Xi H, Li C, Lee S, Xu J, Khurana JS, Zhang F, Schultz N, Koppetsch BS, Nowosielska A et al (2009) The Drosophila HP1 homolog Rhino is required for transposon silencing and piRNA production by dual-strand clusters. Cell 138:1137-1149
87. Kotaja N, Sassone-Corsi P (2007) The chromatoid body: a germ-cell-specific RNA-processing centre. Nat Rev Mol Cell Biol 8:85-90
88. Krawetz SA, Kruger A, Lalancette C, Tagett R, Anton E, Draghici S, Diamond MP (2011) A survey of small RNAs in human sperm. Hum Reprod 26:3401-3412
89. Kuramochi-Miyagawa S, Watanabe T, Gotoh K, Takamatsu K, Chuma S, Kojima-Kita K, Shiromoto Y, Asada N, Toyoda A, Fujiyama A et al (2010) MVH in piRNA processing and gene silencing of retrotransposons. Genes Dev 24:887-892
90. Kuramochi-Miyagawa S, Watanabe T, Gotoh K, Totoki Y, Toyoda A, Ikawa M, Asada N, Kojima K, Yamaguchi Y, Ijiri TW et al (2008) DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes. Genes Dev 22:908-917
91. Lane N, Dean W, Erhardt S, Hajkova P, Surani A, Walter J, Reik W (2003) Resistance of IAPs to methylation reprogramming may provide a mechanism for epigenetic inheritance in the mouse. Genesis 35:88-93
92. Lau NC (2010) Small RNAs in the animal gonad: guarding genomes and guiding development. Int J Biochem Cell Biol 42:1334-1347
93. Lau NC, Ohsumi T, Borowsky M, Kingston RE, Blower MD (2009) Systematic and single cell analysis of Xenopus Piwi-interacting RNAs and Xiwi. EMBO J 28:2945-2958
94. Lau NC, Seto AG, Kim J, Kuramochi-Miyagawa S, Nakano T, Bartel DP, Kingston RE (2006) Characterization of the piRNA complex from rat testes. Science 313:363-367
95. Le Thomas A, Rogers AK, Webster A, Marinov GK, Liao SE, Perkins EM, Hur JK, Aravin AA, Toth KF (2013) Piwi induces piRNA-guided transcriptional silencing and establishment of a repressive chromatin state. Genes Dev 27:390-399
96. Lee EJ, Banerjee S, Zhou H, Jammalamadaka A, Arcila M, Manjunath BS, Kosik KS (2011) Identification of piRNAs in the central nervous system. RNA 17:1090-1099
97. Lee HC, Gu W, Shirayama M, Youngman E, Conte D Jr, Mello CC (2012) C. elegans piRNAs mediate the genome-wide surveillance of germline transcripts. Cell 150:78-87
98. Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75:843-854
99. Lehmann R, Nusslein-Volhard C (1991) The maternal gene nanos has a central role in posterior pattern formation of the Drosophila embryo. Development 112:679-691
100. Li C, Vagin VV, Lee S, Xu J, Ma S, Xi H, Seitz H, Horwich MD, Syrzycka M, Honda BM et al (2009) Collapse of germline piRNAs in the absence of Argonaute3 reveals somatic piRNAs in flies. Cell 137:509-521
101. Li XZ, Roy CK, Dong X, Bolcun-Filas E, Wang J, Han BW, Xu J, Moore MJ, Schimenti JC, Weng Z et al (2013) An ancient transcription factor initiates the burst of piRNA production during early meiosis in mouse testes. Mol Cell 50:67-81
102. Lim AK, Kai T (2007) Unique germ-line organelle, nuage, functions to repress selfish genetic elements in Drosophila melanogaster. Proc Natl Acad Sci U S A 104:6714-6719
103. Lin H, Spradling AC (1997) A novel group of pumilio mutations affects the asymmetric division of germline stem cells in the Drosophila ovary. Development 124:2463-2476
104. Liu J, Carmell MA, Rivas FV, Marsden CG, Thomson JM, Song JJ, Hammond SM, Joshua-Tor L, Hannon GJ (2004) Argonaute2 is the catalytic engine of mammalian RNAi. Science 305: 1437-1441
105. Liu L, Qi H, Wang J, Lin H (2011) PAPI, a novel TUDOR-domain protein, complexes with AGO3, ME31B and TRAL in the nuage to silence transposition. Development 138:1863-1873
106. Lu J, Clark AG (2010) Population dynamics of PIWI-interacting RNAs (piRNAs) and their targets in Drosophila. Genome Res 20:212-227
107. Lu X, Wontakal SN, Kavi H, Kim BJ, Guzzardo PM, Emelyanov AV, Xu N, Hannon GJ, Zavadil J, Fyodorov DV et al (2013) Drosophila H1 regulates the genetic activity of heterochromatin by recruitment of Su(var)3-9. Science 340:78-81
108. Luteijn MJ, van Bergeijk P, Kaaij LJ, Almeida MV, Roovers EF, Berezikov E, Ketting RF (2012) Extremely stable Piwi-induced gene silencing in Caenorhabditis elegans. EMBO J 31: 3422-3430
109. Ma L, Buchold GM, Greenbaum MP, Roy A, Burns KH, Zhu H, Han DY, Harris RA, Coarfa C, Gunaratne PH et al (2009) GASZ is essential for male meiosis and suppression of retrotransposon expression in the male germline. PLoS Genet 5:e1000635
110. Malone CD, Brennecke J, Dus M, Stark A, McCombie WR, Sachidanandam R, Hannon GJ (2009) Specialized piRNA pathways act in germline and somatic tissues of the Drosophila ovary. Cell 137:522-535
111. Marchetto MC, Narvaiza I, Denli AM, Benner C, Lazzarini TA, Nathanson JL, Paquola AC, Desai KN, Herai RH, Weitzman MD et al (2013) Differential L1 regulation in pluripotent stem cells of humans and apes. Nature 503(7477):525-529
112. Megosh HB, Cox DN, Campbell C, Lin H (2006) The role of PIWI and the miRNA machinery in Drosophila germline determination. Curr Biol 16:1884-1894
113. Meister G, Landthaler M, Peters L, Chen PY, Urlaub H, Luhrmann R, Tuschl T (2005) Identification of novel argonaute-associated proteins. Curr Biol 15:2149-2155
114. Mochizuki K, Fine NA, Fujisawa T, Gorovsky MA (2002) Analysis of a piwi-related gene implicates small RNAs in genome rearrangement in tetrahymena. Cell 110:689-699
115. Mochizuki K, Gorovsky MA (2004a) Conjugation-specific small RNAs in Tetrahymena have predicted properties of scan (scn) RNAs involved in genome rearrangement. Genes Dev 18:2068-2073
116. Mochizuki K, Gorovsky MA (2004b) RNA polymerase II localizes in Tetrahymena thermophila meiotic micronuclei when micronuclear transcription associated with genome rearrangement occurs. Eukaryot Cell 3:1233-1240
117. Montgomery TA, Rim YS, Zhang C, Dowen RH, Phillips CM, Fischer SE, Ruvkun G (2012) PIWI associated siRNAs and piRNAs specifically require the Caenorhabditis elegans HEN1 ortholog henn-1. PLoS Genet 8:e1002616
118. Moroz LL, Ju J, Russo JJ, Puthanveetti S, Kohn A, Medina M, Walsh PJ, Birren B, Lander ES, Kandel ER (2009) Aplysia Genome Project. p. 11x coverage sequencing of Aplysia californica genome.
119. Broad Institute Moshkovich N, Lei EP (2010) HP1 recruitment in the absence of argonaute proteins in Drosophila. PLoS Genet 6:e1000880
120. Muerdter F, Guzzardo PM, Gillis J, Luo Y, Yu Y, Chen C, Fekete R, Hannon GJ (2013) A genomewide RNAi screen draws a genetic framework for transposon control and primary piRNA biogenesis in Drosophila. Mol Cell 50(5):736-748
121. Muerdter F, Olovnikov I, Molaro A, Rozhkov NV, Czech B, Gordon A, Hannon GJ, Aravin AA (2012) Production of artificial piRNAs in flies and mice. RNA 18:42-52
122. Nishida KM, Okada TN, Kawamura T, Mituyama T, Kawamura Y, Inagaki S, Huang H, Chen D, Kodama T, Siomi H et al (2009) Functional involvement of Tudor and dPRMT5 in the piRNA processing pathway in Drosophila germlines. EMBO J 28:3820-3831
123. Nishimasu H, Ishizu H, Saito K, Fukuhara S, Kamatani MK, Bonnefond L, Matsumoto N, Nishizawa T, Nakanaga K, Aoki J et al (2012) Structure and function of Zucchini endoribonuclease in piRNA biogenesis. Nature 491:284-287
124. O'Carroll D, Mecklenbrauker I, Das PP, Santana A, Koenig U, Enright AJ, Miska EA, Tarakhovsky A (2007) A Slicer-independent role for Argonaute 2 in hematopoiesis and the microRNA pathway. Genes Dev 21:1999-2004
125. Ohtani H, Iwasaki YW, Shibuya A, Siomi H, Siomi MC, Saito K (2013) DmGTSF1 is necessary for Piwi-piRISC-mediated transcriptional transposon silencing in the Drosophila ovary. Genes Dev 27:1656-1661
126. Okamura K, Lai EC (2008) Endogenous small interfering RNAs in animals. Nat Rev Mol Cell Biol 9:673-678
127. Olivieri D, Senti KA, Subramanian S, Sachidanandam R, Brennecke J (2012) The cochaperone shutdown defines a group of biogenesis factors essential for all piRNA populations in Drosophila. Mol Cell 47:954-969
128. Olivieri D, Sykora MM, Sachidanandam R, Mechtler K, Brennecke J (2010) An in vivo RNAi assay identifies major genetic and cellular requirements for primary piRNA biogenesis in Drosophila. EMBO J 29:3301-3317
129. Pal-Bhadra M, Bhadra U, Birchler JA (2002) RNAi related mechanisms affect both transcriptional and posttranscriptional transgene silencing in Drosophila. Mol Cell 9:315-327
130. Pal Bhadra M, Bhadra U, Birchler JA (2006) Misregulation of sex-lethal and disruption of malespecifi c lethal complex localization in Drosophila species hybrids. Genetics 174:1151-1159
131. Palakodeti D, Smielewska M, Lu YC, Yeo GW, Graveley BR (2008) The PIWI proteins SMEDWI-2 and SMEDWI-3 are required for stem cell function and piRNA expression in planarians. RNA 14:1174-1186
132. Pan J, Goodheart M, Chuma S, Nakatsuji N, Page DC, Wang PJ (2005) RNF17, a component of the mammalian germ cell nuage, is essential for spermiogenesis. Development 132:4029-4039
133. Pane A, Jiang P, Zhao DY, Singh M, Schupbach T (2011) The Cutoff protein regulates piRNA cluster expression and piRNA production in the Drosophila germline. EMBO J 30:4601-4615
134. Pane A, Wehr K, Schupbach T (2007) zucchini and squash encode two putative nucleases required for rasiRNA production in the Drosophila germline. Dev Cell 12:851-862
135. Pao SY, Lin WL, Hwang MJ (2006) In silico identification and comparative analysis of differentially expressed genes in human and mouse tissues. BMC Genomics 7:86
136. Patil VS, Kai T (2010) Repression of retroelements in Drosophila germline via piRNA pathway by the Tudor domain protein Tejas. Curr Biol 20(8):724-730
137. Pavelec DM, Lachowiec J, Duchaine TF, Smith HE, Kennedy S (2009) Requirement for the ERI/ DICER complex in endogenous RNA interference and sperm development in Caenorhabditis elegans. Genetics 183:1283-1295
138. Perrat PN, Das Gupta S, Wang J, Theurkauf W, Weng Z, Rosbash M, Waddell S (2013) Transpositiondriven genomic heterogeneity in the Drosophila brain. Science 340:91-95
139. Petersen CP, Reddien PW (2009) Wnt signaling and the polarity of the primary body axis. Cell 139:1056-1068
140. Post C, Clark J, Sytnikova Y, Chirn GW, Lau NC (2014) The capacity of target silencing by the Drosophila Piwi protein and piRNAs.
141. Submitted Preall JB, Czech B, Guzzardo PM, Muerdter F, Hannon GJ (2012) Shutdown is a component of the Drosophila piRNA biogenesis machinery. RNA 18:1446-1457
142. Rajasethupathy P, Antonov I, Sheridan R, Frey S, Sander C, Tuschl T, Kandel ER (2012) A role for neuronal piRNAs in the epigenetic control of memory-related synaptic plasticity. Cell 149: 693-707
143. Rangan P, Malone CD, Navarro C, Newbold SP, Hayes PS, Sachidanandam R, Hannon GJ, Lehmann R (2011) piRNA production requires heterochromatin formation in Drosophila. Curr Biol 21:1373-1379
144. Ravasi T, Suzuki H, Pang KC, Katayama S, Furuno M, Okunishi R, Fukuda S, Ru K, Frith MC, Gongora MM et al (2006) Experimental validation of the regulated expression of large numbers of non-coding RNAs from the mouse genome. Genome Res 16:11-19
145. Reddien PW, Bermange AL, Kicza AM, Sanchez AA (2007) BMP signaling regulates the dorsal planarian midline and is needed for asymmetric regeneration. Development 134:4043-4051
146. Reinhart BJ, Slack FJ, Basson M, Pasquinelli AE, Bettinger JC, Rougvie AE, Horvitz HR, Ruvkun G (2000) The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 403:901-906
147. Reuter M, Berninger P, Chuma S, Shah H, Hosokawa M, Funaya C, Antony C, Sachidanandam R, Pillai RS (2011) Miwi catalysis is required for piRNA amplification-independent LINE1 transposon silencing. Nature 480:264-267
148. Reuter M, Chuma S, Tanaka T, Franz T, Stark A, Pillai RS (2009) Loss of the Mili-interacting Tudor domain-containing protein-1 activates transposons and alters the Mili-associated small RNA profile. Nat Struct Mol Biol 16:639-646
149. Robine N, Lau NC, Balla S, Jin Z, Okamura K, Kuramochi-Miyagawa S, Blower MD, Lai EC (2009) A broadly conserved pathway generates 3′UTR-directed primary piRNAs. Curr Biol 19:2066-2076
150. Rouget C, Papin C, Boureux A, Meunier AC, Franco B, Robine N, Lai EC, Pelisson A, Simonelig M (2010) Maternal mRNA deadenylation and decay by the piRNA pathway in the early Drosophila embryo. Nature 467:1128-1132
151. Rozhkov NV, Hammell M, Hannon GJ (2013) Multiple roles for Piwi in silencing Drosophila transposons. Genes Dev 27:400-412
152. Ruby JG, Jan C, Player C, Axtell MJ, Lee W, Nusbaum C, Ge H, Bartel DP (2006) Large-scale sequencing reveals 21U-RNAs and additional microRNAs and endogenous siRNAs in C. elegans. Cell 127:1193-1207
153. Saito K, Inagaki S, Mituyama T, Kawamura Y, Ono Y, Sakota E, Kotani H, Asai K, Siomi H, Siomi MC (2009) A regulatory circuit for piwi by the large Maf gene traffic jam in Drosophila. Nature 461:1296-1299
154. Saito K, Ishizu H, Komai M, Kotani H, Kawamura Y, Nishida KM, Siomi H, Siomi MC (2010) Roles for the Yb body components Armitage and Yb in primary piRNA biogenesis in Drosophila. Genes Dev 24:2493-2498
155. Saito K, Nishida KM, Mori T, Kawamura Y, Miyoshi K, Nagami T, Siomi H, Siomi MC (2006) Specific association of Piwi with rasiRNAs derived from retrotransposon and heterochromatic regions in the Drosophila genome. Genes Dev 20:2214-2222
156. Saito K, Sakaguchi Y, Suzuki T, Siomi H, Siomi MC (2007) Pimet, the Drosophila homolog of HEN1, mediates 2′-O-methylation of Piwi-interacting RNAs at their 3′ ends. Genes Dev 21:1603-1608
157. Sato K, Nishida KM, Shibuya A, Siomi MC, Siomi H (2011) Maelstrom coordinates microtubule organization during Drosophila oogenesis through interaction with components of the MTOC. Genes Dev 25:2361-2373
158. Sato K, Siomi H (2010) Is canalization more than just a beautiful idea? Genome Biol 11:109
159. Saxe JP, Chen M, Zhao H, Lin H (2013) Tdrkh is essential for spermatogenesis and participates in primary piRNA biogenesis in the germline. EMBO J 332(13):1869-1885
160. Schoeberl UE, Kurth HM, Noto T, Mochizuki K (2012) Biased transcription and selective degradation of small RNAs shape the pattern of DNA elimination in Tetrahymena. Genes Dev 26:1729-1742
161. Schupbach T, Wieschaus E (1989) Female sterile mutations on the second chromosome of Drosophila melanogaster. I Maternal effect mutations. Genetics 121:101-117
162. Schupbach T, Wieschaus E (1991) Female sterile mutations on the second chromosome of Drosophila melanogaster. II. Mutations blocking oogenesis or altering egg morphology. Genetics 129:1119-1136
163. Sentmanat MF, Elgin SC (2012) Ectopic assembly of heterochromatin in Drosophila melanogaster triggered by transposable elements. Proc Natl Acad Sci U S A 109:14104-14109
164. She X, Xu X, Fedotov A, Kelly WG, Maine EM (2009) Regulation of heterochromatin assembly on unpaired chromosomes during caenorhabditis elegans meiosis by components of a small RNA-mediated pathway. PLoS Genet 5:e1000624
165. Shi Z, Montgomery TA, Qi Y, Ruvkun G (2013) High-throughput sequencing reveals extraordinary fluidity of miRNA, piRNA, and siRNA pathways in nematodes. Genome Res 23:497-508
166. Shirayama M, Seth M, Lee HC, Gu W, Ishidate T, Conte D Jr, Mello CC (2012) piRNAs initiate an epigenetic memory of nonself RNA in the C. elegans germline. Cell 150:65-77
167. Shiromoto Y, Kuramochi-Miyagawa S, Daiba A, Chuma S, Katanaya A, Katsumata A, Nishimura K, Ohtaka M, Nakanishi M, Nakamura T et al (2013) GPAT2, a mitochondrial outer membrane protein, in piRNA biogenesis in germline stem cells. RNA 19:803-810
168. Shoji M, Tanaka T, Hosokawa M, Reuter M, Stark A, Kato Y, Kondoh G, Okawa K, Chujo T, Suzuki T et al (2009) The TDRD9-MIWI2 complex is essential for piRNA-mediated retrotransposon silencing in the mouse male germline. Dev Cell 17:775-787
169. Shpiz S, Kalmykova A (2009) Epigenetic transmission of piRNAs through the female germline. Genome Biol 10:208
170. Sienski G, Donertas D, Brennecke J (2012) Transcriptional silencing of transposons by Piwi and maelstrom and its impact on chromatin state and gene expression. Cell 151:964-980
171. Siomi MC, Mannen T, Siomi H (2010) How does the royal family of Tudor rule the PIWIinteracting RNA pathway? Genes Dev 24:636-646
172. Siomi MC, Sato K, Pezic D, Aravin AA (2011) PIWI-interacting small RNAs: the vanguard of genome defence. Nat Rev Mol Cell Biol 12:246-258
173. Song Y, Fee L, Lee TH, Wharton RP (2007) The molecular chaperone Hsp90 is required for mRNA localization in Drosophila melanogaster embryos. Genetics 176:2213-2222
174. Soper SF, van der Heijden GW, Hardiman TC, Goodheart M, Martin SL, de Boer P, Bortvin A (2008) Mouse maelstrom, a component of nuage, is essential for spermatogenesis and transposon repression in meiosis. Dev Cell 15:285-297
175. Specchia V, Piacentini L, Tritto P, Fanti L, D'Alessandro R, Palumbo G, Pimpinelli S, Bozzetti MP (2010) Hsp90 prevents phenotypic variation by suppressing the mutagenic activity of transposons. Nature 463:662-665
176. Swart EC, Bracht JR, Magrini V, Minx P, Chen X, Zhou Y, Khurana JS, Goldman AD, Nowacki M, Schotanus K et al (2013) The Oxytricha trifallax macronuclear genome: a complex eukaryotic genome with 16,000 tiny chromosomes. PLoS Biol 11:e1001473
177. Sytnikova Y, Lau NC (2013) Does the APC/C Mark MIWI and piRNAs for a final farewell? Dev Cell 24:119-120
178. Sytnikova Y, Rahmam R, Chirn GW, Post C, Clark J, Lau NC (2014) Transposable element dynamics and PIWI regulation impacts lncRNA and gene expression diversity in Drosophila ovarian cell cultures. Submitted Tam OH, Aravin AA, Stein P, Girard A, Murchison EP, Cheloufi S, Hodges E, Anger M, Sachidanandam R, Schultz RM et al (2008) Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes. Nature 453:534-538
179. Toscani A, Mettus RV, Coupland R, Simpkins H, Litvin J, Orth J, Hatton KS, Reddy EP (1997) Arrest of spermatogenesis and defective breast development in mice lacking A-myb. Nature 386:713-717
180. Unhavaithaya Y, Hao Y, Beyret E, Yin H, Kuramochi-Miyagawa S, Nakano T, Lin H (2009) MILI, a PIWI-interacting RNA-binding protein, is required for germ line stem cell self-renewal and appears to positively regulate translation. J Biol Chem 284:6507-6519
181. Vagin VV, Sigova A, Li C, Seitz H, Gvozdev V, Zamore PD (2006) A distinct small RNA pathway silences selfish genetic elements in the germline. Science 313:320-324
182. Vagin VV, Wohlschlegel J, Qu J, Jonsson Z, Huang X, Chuma S, Girard A, Sachidanandam R, Hannon GJ, Aravin AA (2009) Proteomic analysis of murine Piwi proteins reveals a role for arginine methylation in specifying interaction with Tudor family members. Genes Dev 23: 1749-1762
183. van Wolfswinkel JC, Claycomb JM, Batista PJ, Mello CC, Berezikov E, Ketting RF (2009) CDE-1 affects chromosome segregation through uridylation of CSR-1-bound siRNAs. Cell 139: 135-148
184. Vasale JJ, Gu W, Thivierge C, Batista PJ, Claycomb JM, Youngman EM, Duchaine TF, Mello CC, Conte D Jr (2010) Sequential rounds of RNA-dependent RNA transcription drive endogenous small-RNA biogenesis in the ERGO-1/Argonaute pathway. Proc Natl Acad Sci U S A 107:3582-3587
185. Vasileva A, Tiedau D, Firooznia A, Muller-Reichert T, Jessberger R (2009) Tdrd6 is required for spermiogenesis, chromatoid body architecture, and regulation of miRNA expression. Curr Biol 19:630-639
186. Vourekas A, Zheng Q, Alexiou P, Maragkakis M, Kirino Y, Gregory BD, Mourelatos Z (2012) Mili and Miwi target RNA repertoire reveals piRNA biogenesis and function of Miwi in spermiogenesis. Nat Struct Mol Biol 19:773-781
187. Wang C, Dickinson LK, Lehmann R (1994) Genetics of nanos localization in Drosophila. Dev Dyn 199:103-115
188. Wang J, Czech B, Crunk A, Wallace A, Mitreva M, Hannon GJ, Davis RE (2011) Deep small RNA sequencing from the nematode Ascaris reveals conservation, functional diversification, and novel developmental profiles. Genome Res 21:1462-1477
189. Wang J, Saxe JP, Tanaka T, Chuma S, Lin H (2009) Mili interacts with tudor domain-containing protein 1 in regulating spermatogenesis. Curr Biol 19:640-644
190. Wang SH, Elgin SC (2011) Drosophila Piwi functions downstream of piRNA production mediating a chromatin-based transposon silencing mechanism in female germ line. Proc Natl Acad Sci U S A 108:21164-21169
191. Watanabe T, Chuma S, Yamamoto Y, Kuramochi-Miyagawa S, Totoki Y, Toyoda A, Hoki Y, Fujiyama A, Shibata T, Sado T et al (2011) MITOPLD is a mitochondrial protein essential for nuage formation and piRNA biogenesis in the mouse germline. Dev Cell 20:364-375
192. Watanabe T, Totoki Y, Toyoda A, Kaneda M, Kuramochi-Miyagawa S, Obata Y, Chiba H, Kohara Y, Kono T, Nakano T et al (2008) Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes. Nature 453:539-543
193. Wilson JE, Connell JE, Macdonald PM (1996) aubergine enhances oskar translation in the Drosophila ovary. Development 122:1631-1639
194. Xiol J, Cora E, Koglgruber R, Chuma S, Subramanian S, Hosokawa M, Reuter M, Yang Z, Berninger P, Palencia A et al (2012) A role for Fkbp6 and the chaperone machinery in piRNA amplification and transposon silencing. Mol Cell 47:970-979
195. Yabuta Y, Ohta H, Abe T, Kurimoto K, Chuma S, Saitou M (2011) TDRD5 is required for retrotransposon silencing, chromatoid body assembly, and spermiogenesis in mice. J Cell Biol 192:781-795
196. Yan Z, Hu HY, Jiang X, Maierhofer V, Neb E, He L, Hu Y, Hu H, Li N, Chen W et al (2011) Widespread expression of piRNA-like molecules in somatic tissues. Nucleic Acids Res 39:6596-6607
197. Yeo G, Holste D, Kreiman G, Burge CB (2004) Variation in alternative splicing across human tissues. Genome Biol 5:R74
198. Yigit E, Batista PJ, Bei Y, Pang KM, Chen CC, Tolia NH, Joshua-Tor L, Mitani S, Simard MJ, Mello CC (2006) Analysis of the C. elegans Argonaute family reveals that distinct Argonautes act sequentially during RNAi. Cell 127:747-757
199. Yin H, Lin H (2007) An epigenetic activation role of Piwi and a Piwi-associated piRNA in Drosophila melanogaster. Nature 450:304-308
200. Zamparini AL, Davis MY, Malone CD, Vieira E, Zavadil J, Sachidanandam R, Hannon GJ, Lehmann R (2011) Vreteno, a gonad-specific protein, is essential for germline development and primary piRNA biogenesis in Drosophila. Development 138:4039-4050
201. Zhang C, Montgomery TA, Gabel HW, Fischer SE, Phillips CM, Fahlgren N, Sullivan CM, Carrington JC, Ruvkun G (2011a) mut-16 and other mutator class genes modulate 22G and 26G siRNA pathways in Caenorhabditis elegans. Proc Natl Acad Sci U S A 108:1201-1208
202. Zhang F, Wang J, Xu J, Zhang Z, Koppetsch BS, Schultz N, Vreven T, Meignin C, Davis I, Zamore PD et al (2012) UAP56 couples piRNA clusters to the perinuclear transposon silencing machinery. Cell 151:871-884
203. Zhang Z, Xu J, Koppetsch BS, Wang J, Tipping C, Ma S, Weng Z, Theurkauf WE, Zamore PD (2011b) Heterotypic piRNA Ping-Pong requires qin, a protein with both E3 ligase and Tudor domains. Mol Cell 44:572-584
204. Zhao S, Gou LT, Zhang M, Zu LD, Hua MM, Hua Y, Shi HJ, Li Y, Li J, Li D et al (2013) piRNAtriggered MIWI ubiquitination and removal by APC/C in late spermatogenesis. Dev Cell 24:13-25
205. Zheng K, Xiol J, Reuter M, Eckardt S, Leu NA, McLaughlin KJ, Stark A, Sachidanandam R, Pillai RS, Wang PJ (2010) Mouse MOV10L1 associates with Piwi proteins and is an essential component of the Piwi-interacting RNA (piRNA) pathway. Proc Natl Acad Sci U S A 107:11841-11846
206. Zhu W, Pao GM, Satoh A, Cummings G, Monaghan JR, Harkins TT, Bryant SV, Randal Voss S, Gardiner DM, Hunter T (2012) Activation of germline-specific genes is required for limb regeneration in the Mexican axolotl. Dev Biol 370:42-51