Functional redundancy among Nanos proteins and a distinct role of Nanos2 during male germ cell development
Functional redundancy among Nanos proteins and a distinct role of Nanos2 during male germ cell development
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DOI：
10.1242/dev.02697
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发表时间：
2007-01-01
期刊：
影响因子：
4.6
通讯作者：
Saga, Yumiko
中科院分区：
文献类型：
--
作者：
Suzuki, Atsushi;Tsuda, Masayuki;Saga, Yumiko
小鼠Nanos蛋白Nanos2和Nanos3是生殖细胞发育所必需的，并且共享高度保守的锌指结构域。然而，这些因子在发育过程中的表达模式彼此不同。小鼠胚胎中的Nanos3表达在原始生殖细胞（PGCs）形成后立即开始，这种蛋白质的丢失导致两性中的生殖细胞较少的表型。相比之下，Nanos 2表达仅在进入生殖嵴后的雄性PGC中开始，并且这种蛋白质的丢失导致雄性生殖细胞缺陷，而不管Nanos 3在这些细胞中的共表达。这些结果表明，这两种Nanos蛋白具有不同的功能，这取决于它们表达的时间和地点。为了进一步阐明这一点，我们已经产生了在Oct4 Delta PE启动子的控制下表达Nanos2的转基因小鼠品系，并在Nanos3无效的遗传背景下检查了Nanos2的功能。我们发现异位产生的Nanos2蛋白拯救了Nanos3缺失的缺陷，因为生殖细胞在转基因小鼠的两性中完全发育。这一结果表明，Nanos2可以在早期PGC发育过程中替代Nanos3。相比之下，我们目前的数据表明，Nanos3不能挽救Nanos2缺失小鼠的缺陷。因此，我们目前的研究结果表明，Nanos蛋白在早期PGC发育中具有冗余功能，但Nanos 2在小鼠雄性生殖细胞发育过程中具有独特的功能。
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 Delta 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.