36. Sonnichsen B, Koski LB, Walsh A, Marschall P, Neumann B, et al. (2005) Full- genome RNAi profiling of early embryogenesis in Caenorhabditis elegans. Nature 434: 462–469. 37. Hodgkin JA, Horvitz HR, Brenner S (1979) Nondisjunction mutants of the nematode Caenorhabditis elegans. Genetics 91: 67–94. 38. Ward S, Carrel JS (1979) Fertilization and sperm competition in the nematode Caenorhabditis elegans. Dev Biol 73: 304–321. 39. Wolf N, Hirsh D, McIntosh JR (1978) Spermatogenesis in males of the free- living nematode, Caenorhabditis elegans. J Ultrastruct Res 63: 155–169. 40. Ward S, Argon Y, Nelson GA (1981) Sperm morphogenesis in wild-type and fertilization-defective mutants of Caenorhabditis elegans. J Cell Biol 91: 26–44. 41. Nelson GA, Ward S (1980) Vesicle fusion, pseudopod extension and amoeboid motility are induced in nematode spermatids by the ionophore monensin. Cell 19: 457–464. 42. Ward S, Hogan E, Nelson GA (1983) The initiation of spermiogenesis in the nematode Caenorhabditis elegans. Dev Biol 98: 70–79. 43. Shakes DC, Ward S (1989) Initiation of spermiogenesis in C. elegans: a pharmacological and genetic analysis. Dev Biol 134: 189–200. 44. Wicks SR, Yeh RT, Gish WR, Waterston RH, Plasterk RH (2001) Rapid gene mapping in Caenorhabditis elegans using a high density polymorphism map. Nat Genet 28: 160–164. 45. Hirsh D, Oppenheim D, Klass M (1976) Development of the reproductive system of Caenorhabditis elegans. Dev Biol 49: 200–219. 46. Berry LW, Westlund B, Schedl T (1997) Germ-line tumor formation caused by activation of glp-1, a Caenorhabditis elegans member of the Notch family of receptors. Development 124: 925–936. 47. Francis R, Barton MK, Kimble J, Schedl T (1995) gld-1, a tumor suppressor gene required for oocyte development in Caenorhabditis elegans. Genetics 139: 579–606. 48. Subramanian K, Seydoux G (2003) Dedifferentiation of primary spermatocytes into germ cell tumors in C. elegans lacking the pumilio-like protein PUF-8. Curr Biol 13: 134–139. 49. Mello CC, Kramer JM, Stinchcomb D, Ambros V (1991) Efficient gene transfer in C. elegans: extrachromosomal maintenance and integration of transforming sequences. EMBO J 10: 3959–3970. 50. McKay SJ, Johnsen R, Khattra J, Asano J, Baillie DL, et al. (2004) Gene expression profiling of cells, tissues and developmental stages of the nematode C. elegans. Cold Spring Harb Symp Quant Biol 68: 159–169. 51. Lois LM, Lima CD (2005) Structures of the SUMO E1 provide mechanistic insights into SUMO activation and E2 recruitment to E1. EMBO J 24: 439–451. 52. Walden H, Podgorski MS, Schulman BA (2003) Insights into the ubiquitin transfer cascade from the structure of the activating enzyme for NEDD8. Nature 422: 330–334. 53. Kitagawa R, Law E, Tang L, Rose AM (2002) The Cdc20 homolog, FZY-1, and its interacting protein, IFY-1, are required for proper chromosome segregation in Caenorhabditis elegans. Curr Biol 12: 2118–2123. 54. Lin R (2003) A gain-of-function mutation in oma-1, a C. elegans gene required for oocyte maturation, results in delayed degradation of maternal proteins and embryonic lethality. Dev Biol 258: 226–239. 55. Kipreos ET (2005) Ubiquitin-mediated pathways. In: The C. elegans Research Community, editors. WormBook, Available: http://www.wormbook.org. 56. Savage C, Das P, Finelli AL, Townsend SR, Sun CY, et al. (1996) Caenorhabditis elegans genes sma-2, sma-3, and sma-4 define a conserved family of transforming growth factor beta pathway components. Proc Natl Acad Sci U S A 93: 790–794. 57. Suzuki Y, Yandell MD, Roy PJ, Krishna S, Savage-Dunn C, et al. (1999) A BMP homolog acts as a dose-dependent regulator of body size and male tail patterning in Caenorhabditis elegans. Development 126: 241–250. UBA-1 in C. elegans Development 58. Itoh S, ten Dijke P (2007) Negative regulation of TGF-beta receptor/Smad signal transduction. Curr Opin Cell Biol 19: 176–184. 59. Baarends WM, Hoogerbrugge JW, Roest HP, Ooms M, Vreeburg J, et al. (1999) Histone ubiquitination and chromatin remodeling in mouse spermatogenesis. Dev Biol 207: 322–333. 60. Sutovsky P, Moreno R, Ramalho-Santos J, Dominko T, Thompson WE, et al. (2001) A putative, ubiquitin-dependent mechanism for the recognition and elimination of defective spermatozoa in the mammalian epididymis. J Cell Sci 114: 1665–1675. 61. Guardavaccaro D, Kudo Y, Boulaire J, Barchi M, Busino L, et al. (2003) Control of meiotic and mitotic progression by the F box protein beta-Trcp1 in vivo. Dev Cell 4: 799–812. 62. Morokuma Y, Nakamura N, Kato A, Notoya M, Yamamoto Y, et al. (2007) MARCH-XI, a novel transmembrane ubiquitin ligase implicated in ubiquitin- dependent protein sorting in developing spermatids. J Biol Chem 282: 24806–24815. 63. Kelleher JF, Mandell MA, Moulder G, Hill KL, L’Hernault SW, et al. (2000) Myosin VI is required for asymmetric segregation of cellular components during C. elegans spermatogenesis. Curr Biol 10: 1489–1496. 64. Sawada H, Sakai N, Abe Y, Tanaka E, Takahashi Y, et al. (2002) Extracellular ubiquitination and proteasome-mediated degradation of the ascidian sperm receptor. Proc Natl Acad Sci U S A 99: 1223–1228. 65. Slack FJ, Basson M, Liu Z, Ambros V, Horvitz HR, et al. (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. 66. del Rio-Albrechtsen T, Kiontke K, Chiou SY, Fitch DH (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. 67. Baird SE, Ellazar SA (1999) TGFbeta-like signaling and spicule development in Caenorhabditis elegans. Dev Biol 212: 93–100. 68. Howard RA, Sharma P, Hajjar C, Caldwell KA, Caldwell GA, et al. (2007) Ubiquitin conjugating enzymes participate in polyglutamine protein aggrega- tion. BMC Cell Biol 8: 32. 69. Hoppe T, Cassata G, Barral JM, Springer W, Hutagalung AH, et al. (2004) Regulation of the myosin-directed chaperone UNC-45 by a novel E3/E4- multiubiquitylation complex in C. elegans. Cell 118: 337–349. 70. Liao EH, Hung W, Abrams B, Zhen M (2004) An SCF-like ubiquitin ligase complex that controls presynaptic differentiation. Nature 430: 345–350. 71. Mehta N, Loria PM, Hobert O (2004) A genetic screen for neurite outgrowth mutants in Caenorhabditis elegans reveals a new function for the F-box ubiquitin ligase component LIN-23. Genetics 166: 1253–1267. 72. Ding M, Chao D, Wang G, Shen K (2007) Spatial regulation of an E3 ubiquitin ligase directs selective synapse elimination. Science 317: 947–951. 73. Hodgkin J (1987) A genetic analysis of the sex-determining gene, tra-1, in the nematode Caenorhabditis elegans. Genes Dev 1: 731–745. 74. Hansen D, Pilgrim D (1999) Sex and the single worm: sex determination in the nematode C. elegans. Mech Dev 83: 3–15. 75. Brenner S (1974) The genetics of Caenorhabditis elegans. Genetics 77: 71–94. 76. Hill KL, L’Hernault SW (2001) Analyses of reproductive interactions that occur after heterospecific matings within the genus Caenorhabditis. Dev Biol 232: 105–114. 77. Timmons L, Fire A (1998) Specific interference by ingested dsRNA. Nature 395: 854. 78. Lee MH, Schedl T (2006) RNA in situ hybridization of dissected gonads. In: The C. elegans Research Community, editors. WormBook, Available: http://www. wormbook.org. PLoS Genetics | www.plosgenetics.org 13 July 2008 | Volume 4 | Issue 7 | e1000131