49. High FA, Epstein JA (2008) The multifaceted role of Notch in cardiac development and disease. Nature Rev. Genet 9: 49–61. 50. Chartier A, Zaffran S, Astier M, Semeriva M, Gratecos D (2002) Pericardin, a Drosophila type IV collagen-like protein is involved in the morphogenesis and maintenance of the heart epithelium during dorsal ectoderm closure. Development 129: 3241–3253. 51. Albrecht S, Wang S, Holz A, Bergter A, Paululat A (2006) The ADAM metalloprotease Kuzbanian is crucial for proper heart formation in Drosophila melanogaster. Mech. Dev 123: 372–387. 52. Pazdera TM, Janardhan P, Minden JS (1998) Patterned epidermal cell death in wild-type and segment polarity mutant Drosophila embryos. Development 125: 3427–3436. 53. Lyman D, Young MW (1993) Further evidence for function of the Drosophila Notch protein as a transmembrane receptor. Proc. Natl. Acad. Sci. U S A 90: 10395–10399. 54. Fehon RG, Kooh PJ, Rebay I, Regan CL, Xu T, et al. (1990) Molecular interaction between the protein products of the neurogenic loci Notch and Delta, two EGF-homologous genes in Drosophila. Cell 61: 523–534. 55. Parks AL, Kleug KM, Stout JR, Muskavitch MA (2000) Ligand endocytosis drives receptor dissociation and activation in the Notch pathway. Development 127: 1373–1385. 56. Mishra-Gorur K, Rand MD, Perez-Villamil B, Artavanis-Tsakonas S (2002) Down-regulation of Delta by proteolytic processing. J Cell. Biol. 159: 313–324. 57. Wesley CS, Saez L (2000) Notch responds differently to Delta and Wingless in cultured Drosophila cells. J Biol. Chem 275(13): 9099–9101. 58. Lieber T, Kidd S, Alcamo E, Corbin V, Young MW (1993) Antineurogenic phenotypes induced by truncated Notch proteins indicate a role in signal transduction and may point to a novel function for Notch in nuclei. Genes Dev 7: 1949–1965. 59. Struhl G, Fitzgerald K, Greenwald I (1993) Intrinsic activity of the Lin-12 and Notch intracellular domains in vivo. Cell 74: 331–345. 60. Wilkin MB, Carbery AM, Fostier M, Aslam H, Mazaleyrat SL et al. (2004) Regulation of notch endosomal sorting and signaling by Drosophila Nedd4 family proteins. Curr. Biol 14: 2237–44. 61. Sakata T, Sakaguchi H, Tsuda L, Higashitani A, Aigaki T, et al. (2004) Drosophila Nedd4 regulates endocytosis of notch and suppresses its ligand- independent activation. Curr. Biol 14: 2228–36. 62. Berechid BE, Kitzmann M, Foltz DR, Roach AH, Seiffert D, et al. (2002) Identification and characterization of presenilin-independent Notch signaling. J Biol. Chem 277: 8154–8165. 63. Oren-Suissa M, Podbilewicz B (2007) Cell fusions during development. Trends Cell Biol 17: doi 10.1016. 64. Robida M, Sridharan V, Morgan S, Rao T, Singh R (2010) Drosophila polypyrimidine tract-binding protein is necessary for spermatid individualiza- tion. Proc. Natl. Acad. Sci. U S A 107: 12570–5. Notch and Actin Zones in Drosophila Embryos 65. Cross DP, Sang JH (1978) Cell culture of individual Drosophila embryos. II. Culture of X-linked embryonic lethals. J Embryol. Exp. Morphol 45: 173–187. 66. Baker R, Schubiger G (1996) Autonomous and nonautonomous Notch functions for embryonic muscle and epidermis development in Drosophila. Development 122: 617–626. 67. Irvine KD, Wieschaus E (1994) fringe, a boundary-specific signaling molecule, mediates interactions between dorsal and ventral cells during Drosophila wing development. Cell 79: 595–606. 68. Wilkin MB, Carbery AM, Fostier M, Aslam H, Mazaleyrat SL, et al. (2004) Regulation of notch endosomal sorting and signaling by Drosophila Nedd4 family proteins. Curr. Biol 14: 2237–44. 69. Sakata T, Sakaguchi H, Tsuda L, Higashitani A, Aigaki T, et al. (2004) Drosophila Nedd4 regulates endocytosis of notch and suppresses its ligand- independent activation. Curr. Biol 14: 2228–36. 70. Moloney DJ, Panin VM, Johnston SH, Chen J, Shao L, et al. (2000) Fringe is a glycosyltransferase that modifies Notch. Nature 406: 369–375. 71. Panin VM, Shao L, Lei L, Moloney DJ, Irvine KD, et al. (2002) Notch ligands are substrates for protein O-Fucosyltransferase-1 and Fringe. J Biol. Chem. 277: 29945–29952. 72. Bruckner K, Perez L, Claussen H, Cohen S (2000) Glycosyltransferase activity of Fringe modulates Notch-Delta interactions. Nature 406: 411–415. 73. Pavlopoulos E, Pitsouli C, Kleug KM, Muskavitch MA, Moschonas NK, et al. (2001) Neuralized encodes a peripheral membrane protein involved in delta signaling and endocytosis. Dev. Cell 1: 807–816. 74. Lai EC, Deblandre GA, Kintner C, Rubin GM (2001) Drosophila Neuralized is a ubiquitin ligase that promotes the interanalization and degradation of Delta. Dev. Cell 1: 783–794. 75. Le Borgne R, Bardin A, Schweisguth F (2005) The roles of receptor and ligand endocytosis in regulating Notch signaling. Development 132: 1751–1762. 76. Wang W, Struhl G (2005) Distinct roles for mind bomb, Neuralized and Epsin in mediating DSL endocytosis and signaling in Drosophila. Development 132: 2882–2894. 77. Wang W, Struhl G (2004) Drosophila Epsin mediates a select endocytic pathway that DSL ligands must enter to activate Notch. Development 131: 5367–5380. 78. Emery G, Hutterer A, Berdnik D, Mayer B, Wirtz-Peittz F, et al. (2005) Asymmetric Rab11 endosomes regulate Delta recycling and specify cell fate in the Drosophila nervous system. Cell 122: 763–773. 79. Hori K, Forstier M, Ito M, Fuwa TJ, Go MJ, et al. (2004) Drosophila Deltex mediates suppressor of Hairless-independent and late endosomal activation of Notch signaling. Development 131: 5527–5537. 80. Wilkin MB, Baron M (2005) Endocytic regulation of Notch activation and down-regulation. Mol. Membr. Biol 22: 279–289. 81. Sapir A, Assa-Kunik E, Tsruya R, Schejter E, Shilo B (2005) Unidirectional Notch signaling depends on continuous cleavage of Delta. Development 132(1): 123–132. PLoS ONE | www.plosone.org 15 July 2011 | Volume 6 | Issue 7 | e21876