Translational repression restricts expression of the C. elegans Nanos homolog NOS-2 to the embryonic germline. D'Agostino I et al. Members of the nanos gene family are evolutionarily conserved regulators of germ cell development. In several organisms, Nanos protein expression is restricted to the primordial germ cells (PGCs) during early embryogenesis. Here, we investigate the regulation of the Caenorhabditis elegans nanos homolog nos-2. We find that the nos-2 RNA is translationally repressed. In the adult germline, translation of the nos-2 RNA is inhibited in growing oocytes, and this inhibition depends on a short stem loop in the nos-2 3'UTR. In embryos, nos-2 translation is repressed in early blastomeres, and this inhibition depends on a second region in the nos-2 3'UTR. nos-2 RNA is also degraded in somatic blastomeres by a process that is independent of translational repression and requires the CCCH finger proteins MEX-5 and MEX-6. Finally, the germ plasm component POS-1 activates nos-2 translation in the PGCs. A combination of translational repression, RNA degradation, and activation by germ plasm has also been implicated in the regulation of nanos homologs in Drosophila and zebrafish, suggesting the existence of conserved mechanisms to restrict Nanos expression to the germline.
General function
Cell proliferation, RNA processing, RNA binding
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Cellular localization
Cytoplasmic, Nuclear
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Ovarian function
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Expression regulated by
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Ovarian localization
Primordial Germ Cell, Oocyte
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Implication of nanos2-3'UTR in the expression and function of nanos2. Tsuda M et al. Translational control of gene expression is an important component of the regulation of cellular differentiation and development. To elucidate the function of the 3'untranslated region (UTR) of the nanos2 gene in mice, we compared the phenotypes of lacZ knock-in mice with or without a native nanos2 3'UTR and found that this region of the nanos2 gene has a potential role during translational regulation in germ cells. The nanos2-3'UTR functions to repress the translation of mRNA in oocytes, but enhances the production of protein in the male gonads. To further understand the significance of the nanos2 3'UTR in vivo, we generated the mouse line nanos2(pA/pA), which lacks this region endogenously. In nanos2(-/pA) mice, the number of germ cell-depleted seminiferous tubules was increased when compared with that of nanos2(pA/pA) mice, indicating a dose-dependent defect in spermatogenesis. These results suggest that the level of nanos2 protein is critical for normal spermatogenesis, and that this pathway may be regulated through the nanos2-3'UTR. We found that the defects in nanos2(pA/pA) and nanos2(-/pA) mice were caused by apoptosis of gonocytes in the embryonic gonads and gonocyte/spermatogonia in neonatal testes. In addition, it was noted that the nanos2 expression was restricted to a particular subset of spermatogonia after birth, which indicates that nanos2 plays a role in the maintenance and differentiation of gonocytes/spermatogonia in neonatal testes.
Follicle stages
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Phenotypes
Mutations
1 mutations
Species: mouse
Mutation name: type: null mutation fertility: fertile Comment: Conserved role of nanos proteins in germ cell development. Tsuda M et al. (2003) In Drosophila, maternally supplied Nanos functions in the migration of primordial germ cells (PGCs) into the gonad; in mice, zygotic genes are involved instead. We report the cloning and the functional analyses of nanos2 and nanos3 in mice. These genes are differentially expressed in mouse PGCs. nanos2 is predominantly expressed in male germ cells, and the elimination of this gene results in a complete loss of spermatogonia. However, nanos3 is found in migrating PGCs, and the elimination of this factor results in the complete loss of germ cells in both sexes. Hence, although mice and flies differ in their mechanisms for germ cell specification, there seems to be conserved function for nanos proteins among invertebrates and vertebrates.//////////////////OMIM: Tsuda et al. (2003) found that Nanos2-null mice were viable and showed no apparent abnormalities, but Nanos2-null testes had defects in spermatogenesis. The weight of testes in 4-week-old mutant males was reduced to about 30% of normal, and no germ cells were detected. Morphologic examination revealed apoptotic germ cells after embryonic day 15.5, and apoptosis continued until the germ cells had completely disappeared by 4 weeks of age. In contrast, female gonads were morphologically and functionally normal, and homozygous female mice were fertile.