Functional redundancy among Nanos proteins and a distinct role of Nanos2 during male germ cell development

Abstract

The mouse Nanos proteins, Nanos2 and Nanos3, are required for germ cell development and share a highly conserved zinc-finger domain. The expression patterns of these factors during development, however, differ from each other. Nanos3 expression in the mouse embryo commences in the primordial germ cells (PGCs) just after their formation, and a loss of this protein results in the germ cell-less phenotype in both sexes. By contrast, Nanos2 expression begins only in male PGCs after their entry into the genital ridge and a loss of this protein results in a male germ cell deficiency, irrespective of the co-expression of Nanos3 in these cells. These results indicate that these two Nanos proteins have distinct functions, which depend on the time and place of their expression. To further elucidate this, we have generated transgenic mouse lines that express Nanos2 under the control of the Oct4⌬PE promoter and examined Nanos2 function in a Nanos3-null genetic background. We find that ectopically produced Nanos2 protein rescues the Nanos3-null defects, because the germ cells fully develop in both sexes in the transgenic mice. This result indicates that Nanos2 can substitute for Nanos3 during early PGC development. By contrast, our current data show that Nanos3 does not rescue the defects in Nanos2-null mice. Our present findings thus indicate that there are redundant functions of the Nanos proteins in early PGC development, but that Nanos2 has a distinct function during male germ cell development in the mouse.

Targeted gene silencing in mouse germ cells by insertion of a homologous DNA into a piRNA generating locus

“…The repression was orientation-dependent, and the reporter gene complementary to the piRNAs was more effectively repressed, suggesting that it was, indeed, dependent on piRNA generation. Considering the studies on other transgenes in the mouse testis (Wang et al 2006;Suzuki et al 2007), we believe that transgene insertions outside of piRNA generating regions would not result in a silencing effect. The repression was, at least in part, due to accelerated degradation of the target RNA (PTGS) and clearly dependent on the piRNA pathway, as overexpression of PIWIL2 enhanced the repression.…”

NANOS2 interacts with the CCR4-NOT deadenylation complex and leads to suppression of specific RNAs

“…In further immunoprecipitation experiments, we used a transgenic mouse line expressing a FLAG-tagged NANOS2 under the direct control of the Nanos2 enhancer (15) (Fig. S5A), since we had confirmed that this fusion protein was functional (Fig.…”

Foetal germ cells: striking the balance between pluripotency and differentiation

“…SCF/cKIT signalling is required for proliferation and survival of germ cells and aberrant function of this pathway has been associated with abnormal proliferation and transformation of germ cells Godin and Wylie, 1991;Matsui et al, 1991;Dolci et al, 1993;Pesce et al, 1993;Donovan and de Miguel, 2003;Sakuma et al, 2003;McIntyre et al, 2005;Goddard et al, 2007). Two members of the NANOS family of RNA binding proteins, NANOS2 and NANOS3 are also required for survival of foetal germ cells (Tsuda et al, 2003;Suzuki et al, 2007). Nanos3 is expressed in migrating germ cells and functions to maintain early germ cell survival, at least partly through suppression of apoptosis , while Nanos2 is male specifically expressed and required for survival and differentiation of gonadal germ cells (Suzuki et.…”