Nanos interacts with Cup

Nanos (Nos) has at least five different functions during the development of Drosophila melanogaster. In the pre-cellular blastoderm embryo, maternally derived Nos is required for formation of abdominal segments (Wang and Lehmann, 1991). Subsequently, maternal Nos is required in the embryonic germline precursors, the pole cells, to inhibit their division and promote migration into the somatic gonad (Asaoka-Taguchi et al., 1999; Forbes and Lehmann, 1998; Kobayashi et al., 1996). Zygotically expressed Nos is required for maintenance of germ line stem cells in females (Forbes and Lehmann, 1998) and males (Bhat, 1999). And finally, Nos is required for viability of the adult (Spradling et al., 1999). These roles have been revealed by the analysis of various nos mutant alleles, which have different molecular lesions and attendant phenotypic consequences. The molecular mechanism of Nos action is best understood for its role in promoting abdominal segmentation of the embryo. In collaboration with Pumilio (Pum), Nos acts to inhibit the translation of hunchback (hb) mRNA in the posterior of the embryo (Sonoda and Wharton, 1999). Pum is a site-specific RNA-binding protein that recognizes the crucial cis-acting targets in the 3′UTR of hb mRNA (Wharton et al., 1998; Zamore et al., 1997). Nos is subsequently recruited via protein-protein and protein-RNA contacts (Sonoda and Wharton, 1999), and the resulting Pum-Nos complex inhibits translation by as yet unknown mechanisms, although inhibition is accompanied by deadenylation of the mRNA (Wharton and Struhl, 1991; Wreden et al., 1997). In contrast, little is known of how Nos acts in other cell types during development. Recent work suggests that Nos and Pum also collaborate to regulate Cyclin B (CycB) mRNA in the pole cells and thereby control their division (Asaoka-Taguchi et al., 1999; Deshpande et al., 1999); however, direct interactions of Nos and Pum with CycB mRNA have not been reported. In the germline stem cells, the targets of Nos action are not yet known. Moreover, it is unclear whether Nos and Pum act collaboratively in this tissue type. Although germ cells are rapidly lost from the ovaries of flies bearing ‘strong’ alleles of nos (nosRC/Df(nos)) or pum (pumET1/pumMsc), the mutant phenotypes are somewhat different, leading to the suggestion that Nos and Pum may act independently (Forbes and Lehmann, 1998). Finally, the discovery of lethal alleles reveals an essential function for Nos in the larva or adult, but the tissue or cell type that requires Nos activity has not been reported. The function of Nos in germline precursor cells appears to be evolutionarily conserved, at least in part. Nos homologues have been described in Diptera, Xenopus, leech and Caenorhabditis elegans (Curtis et al., 1995; Kraemer et al., 1999; Mosquera et al., 1993; Pilon and Weisblat, 1997; Subramaniam and Seydoux, 1999). Like Drosophila Nos, each Nos homolog is expressed preferentially in the germline precursor cells, consistent with a conserved role. Moreover, recent genetic experiments suggest that Nos and Pum homologs are likely to collaborate to regulate various aspects of germline development in C. elegans. In particular, reduction of Nos1 and Nos2 activity by RNAi causes germ cell phenotypes similar to those seen in nos mutant flies (inefficient incorporation into the gonad, premature proliferation, and elimination of germ cells from the post-embryonic gonad) (Kraemer et al., 1999; Subramaniam and Seydoux, 1999). 5225 Development 127, 5225-5232 (2000) Printed in Great Britain © The Company of Biologists Limited 2000 DEV6481