Tdrd1/Mtr-1, a tudor-related gene, is essential for male germ-cell differentiation and nuage/germinal granule formation in mice
Tdrd1/Mtr-1, a tudor-related gene, is essential for male germ-cell differentiation and nuage/germinal granule formation in mice
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DOI：
10.1073/pnas.0601878103
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发表时间：
2006-10-24
影响因子：
11.1
通讯作者：
Nakatsuji, Norio
中科院分区：
文献类型：
--
作者：
Chuma, Shinichiro;Hosokawa, Mihoko;Nakatsuji, Norio
小鼠的胚胎模式和生殖细胞规格是可调节的并且取决于合子基因活性。然而，果蝇母体效应基因有小鼠同源物，包括 vasa 和 tudor，它们在后细胞和生殖细胞决定中发挥作用。我们在此报告，含有 11mouse tudor 重复序列 1 (Tdrd1/Mtr-1)（小鼠 tudor 相关基因）的 Tudor 结构域中的靶向突变会因出生后生精缺陷而导致雄性不育。 TDRD1/MTR-1主要定位于nuage/生发颗粒，这是种系中进化上保守的结构，并且其细胞内定位是小鼠血管同源bEAD盒多肽4(MMID&4)的下游，类似于果蝇vasa-tudor。 TdrdlIMtr-1 突变体缺乏线粒体间水泥（雄性和雌性生殖细胞中 nuage 的一种形式）的强烈减少，而 MvhlDdx4 突变体则显示，而在 TdrdlIMtr-1 突变体中观察到类染色体（生精细胞中 nuage 的另一种特殊形式）。因此，线粒体间水泥并不是小鼠卵母细胞发育和生育能力的直接先决条件，这表明雄性和雌性生殖细胞对 nuage 和/或其成分的要求不同。结果还表明，类染色质体可能具有独立于线粒体间水泥或附加于线粒体间水泥的起源。小鼠生精细胞中的 Mvh-Tdrdl 与果蝇卵母细胞中的 vasa-tudor 之间的类比表明，该分子途径保留了在不同物种和生殖系的不同阶段/性别中发挥作用的重要作用。
Embryonic patterning and germ-cell specification in mice are regulative and depend on zygotic gene activities. However, there are mouse homologues of Drosophila maternal eff ect genes, including vasa and tudor, that function in posterior and germ-cell determination. We report here that a targeted mutation in Tudor domain containing 11mouse tudor repeat 1 (Tdrd1/Mtr- 1), a tudor-related gene in mice, leads to male sterility because of postnatal spermatogenic defects. TDRDl/MTR-1 predominantly localizes to nuage/ germinal granules, an evolutionarily conserved structure in the germ line, and its intracellular localization is downstream of mouse vasal homologuelbEAD box polypeptide 4 (MMID&4), similar to Drosophiia vasa-tudor. TdrdlIMtr-1 mutants lack, and MvhlDdx4 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 TdrdlIMtr-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-Tdrdl in mouse spermatogenic cells and vasa-tudor in Drosophila oocytes suggests that this molecular pathway retains an essential role(s) that functions in divergent species and in different stages/sexes of the germ line.