title: NANOS2 promotes male germ cell development independent of meiosis suppression.
abstract: NANOS2 is an RNA-binding protein essential for fetal male germ cell development. While we have shown that the function of NANOS2 is vital for suppressing meiosis in embryonic XY germ cells, it is still unknown whether NANOS2 plays other roles in the sexual differentiation of male germ cells. In this study, we addressed the issue by generating Nanos2/Stra8 double knockout (dKO) mice, whereby meiosis was prohibited in the double-mutant male germ cells. We found that the expression of male-specific genes, which was decreased in the Nanos2 mutant, was hardly recovered in the dKO embryo, suggesting that NANOS2 plays a role in male gene expression other than suppression of meiosis. To investigate the molecular events that may be controlled by NANOS2, we conducted a series of microarray analyses to search putative targets of NANOS2 that fulfilled 2 criteria: (1) increased expression in the Nanos2 mutant and (2) the mRNA associated with NANOS2. Interestingly, the genes predominantly expressed in undifferentiated primordial germ cells (PGCs) were significantly selected, implying the involvement of NANOS2 in the termination of the characteristics of PGCs. Furthermore, we showed that NANOS2 is required for the maintenance of mitotic quiescence, but not for the initiation of the quiescence in fetal male germ cells. These results suggest that NANOS2 is not merely a suppressor of meiosis, but instead plays pivotal roles in the sexual differentiation of male germ cells.
authors.affiliation: Division of Mammalian Development, Genetic Strains Research Center, National Institute of Genetics, Yata 1111, Mishima, Shizuoka 411-8540, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Saba
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Kato
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Saga
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis*; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D008297:Male; D008540:Meiosis; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D012733:Sex Differentiation / Q000235:genetics; D015398:Signal Transduction; D013094:Spermatozoa / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C477341:Nanos2 protein, mouse; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C102019:Stra8 protein, mouse
keywords: 5-bromo-2′-deoxyuridine; BrdU; E; IP; Male germ cell; Nanos2; PBS; PCR; PGC; RA; RIP; RNA immunoprecipitation; RT; Stra8; dKO; double knockout; embryonic day; immunoprecipitation; phosphate-buffered saline; polymerase chain reaction; primordial germ cell; retinoic acid; reverse transcription