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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Abstract
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 role(s) that functions in divergent species and in different stages/sexes of the germ line.