Drosophila, like other invertebrates and plants, relies mainly on RNA interference for its defense against viruses. In flies, viral infection also triggers the expression of many genes. One of the genes induced, Vago, encodes a 18-kilodalton cysteine-rich polypeptide. Here we provide genetic evidence that the Vago gene product controlled viral load in the fat body after infection with drosophila C virus. Induction of Vago was dependent on the helicase Dicer-2. Dicer-2 belongs to the same DExD/H-box helicase family as do the RIG-I-like receptors, which sense viral infection and mediate interferon induction in mammals. We propose that this family represents an evolutionary conserved set of sensors that detect viral nucleic acids and direct antiviral responses.

(2) the expression of Foxc1 and Pitx2, which play crucial roles in anterior eye segment development; and (3) the growth of the ventral retina. We additionally show that RALDH1 and RALDH3 are the only enzymes that are required for RA synthesis in the eye region from E10.5 to E13.5, and that patterning of the dorsoventral axis of the retina does not require RA. Research articleDevelopment 4790 role in DV patterning Dräger et al., 2001;Peters and Cepko, 2002;Sakai et al., 2004).RALDH2, whose genetic ablation kills embryos at E9.5 (Niederreither et al., 1999;Mic et al., 2002), is required between E8.5 and E9.5 for optic cup formation and for setting up the correct expression of RALDH3 at later stages in the forming eye (Mic et al., 2004). RALDH1-null mice are viable and do not exhibit ocular defects, even though they lack RAdependent activity in the dorsal retina and in the corresponding axonal projections at E16.5 (Fan et al., 2003). RALDH3-null mice, which die at birth from respiratory distress due to choanal atresia, display only discrete ocular malformations, namely a retrolenticular membrane and a mild shortening of the ventral retina (Dupé et al., 2003). Furthermore, neither RALDH1-null nor RALDH3-null mice exhibit an altered DV patterning of the retina (Fan et al., 2003; Dupé et al., 2003). These observations raised the question as to whether the loss of RALDH1 or RALDH3 could be functionally compensated by RALDH3 or RALDH1, respectively, or by other RALDH proteins expressed in the eye region. To gain further insight into the roles of RA signaling pathways in the developing eye, we have analyzed the ocular phenotype of mutant mice (1) lacking both RALDH1 and RALDH3, and (2) lacking RAR␤ and RAR␥ selectively in the NCC-derived periocular mesenchyme (POM). We demonstrate that RA produced in the neural retina, the retinal pigmented epithelium and the corneal ectoderm by RALDH1 and RALDH3 acts in a paracrine manner to selectively control the expression of several genes in POM cells, whereas it is dispensable for the DV patterning of the retina. Materials and methods MiceAll mice, with a mixed C57BL/6ϫ129/Sv (50:50) genetic background, were housed in an animal facility licensed by the French Ministry of Agriculture , and all animal experiments were supervised by N.B.G. , who is qualified for experimenting with mice, in compliance with the European legislation on care and use of laboratory animals. The breeding diet (D03) contained 25000 UI of vitamin A per kg (UAR, Villemoisson sur Orge, France) and was provided ad libitum. Heterozygous mice were mated overnight, and animals with a vaginal plug at noon of the next day were considered as embryonic day (E) 0.5. Mice bearing loxP-flanked (floxed) RAR␤ (Rarb +/L2) and RAR␥ (Rarg +/L2) genes (Chapellier et al., 2002a; Chapellier, 2002b), as well as the Rare-hsp68-lacZ (Rossant et al., 1991), R26R (Soriano, 1999) and Wnt1-Cre (Danielian et al., 1998) transgenic mice were genotyped as described. Note that mutant fetuses lacking both RALDH1 and RALDH3 (hereafter designa...