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

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.