Tdrd1/Mtr-1 , a tudor -related gene, is essential for male germ-cell differentiation and nuage/germinal granule formation in mice

作者：Shinichiro Chuma, Mihoko Hosokawa, KOUICHI KITAMURA, Shinya Kasai, Makio Fujioka, Masateru Hiyoshi, Kazufumi Takamune, Toshiaki Noce, Norio Nakatsuji · 发表于：Proceedings of the National Academy of Sciences · 年份：2006 · DOI：10.1073/pnas.0601878103 · 被引用次数：246 · 研究领域：Epigenetics and DNA Methylation、Pluripotent Stem Cells Research、Reproductive Biology and Fertility

Embryonic patterning and germ-cell specification in mice are regulative and depend on zygotic gene activities. However, there are mouse homologues of Drosophila maternal effect genes, including vasa and tudor, that function in posterior and germ-cell determination. We report here that a targeted mutation in Tudor domain containing 1/mouse tudor repeat 1 (Tdrd1/Mtr-1), a tudor-related gene in mice, leads to male sterility because of postnatal spermatogenic defects. TDRD1/MTR-1 predominantly localizes to nuage/germinal granules, an evolutionarily conserved structure in the germ line, and its intracellular localization is downstream of mouse vasa homologue/DEAD box polypeptide 4 (Mvh/Ddx4), similar to Drosophila vasa-tudor. Tdrd1/Mtr-1 mutants lack, and Mvh/Ddx4 mutants show, strong reduction of intermitochondrial cement, a form of nuage in both male and female germ cells, whereas chromatoid bodies, another specialized form of nuage in spermatogenic cells, are observed in Tdrd1/Mtr-1 mutants. Hence, intermitochondrial cement is not a direct prerequisite for oocyte development and fertility in mice, indicating differing requirements for nuage and/or its components between male and female germ cells. The result also proposes that chromatoid bodies likely have an origin independent of or additional to intermitochondrial cement. The analogy between Mvh-Tdrd1 in mouse spermatogenic cells and vasa-tudor in Drosophila oocytes suggests that this molecular pathway retains an essential ro...