title: Tdrd1/Mtr-1, a tudor-related gene, is essential for male germ-cell differentiation and nuage/germinal granule formation in mice.
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.
authors.affiliation: Department of Development and Differentiation, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan. schuma@frontier.kyoto-u.ac.jp
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Chuma
authors.forename: Mihoko
authors.initials: M
authors.lastname: Hosokawa
authors.forename: Kouichi
authors.initials: K
authors.lastname: Kitamura
authors.forename: Shinya
authors.initials: S
authors.lastname: Kasai
authors.forename: Makio
authors.initials: M
authors.lastname: Fujioka
authors.forename: Masateru
authors.initials: M
authors.lastname: Hiyoshi
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Takamune
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Noce
authors.forename: Norio
authors.initials: N
authors.lastname: Nakatsuji
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D005260:Female; D005854:Germ Cells / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D016253:Microscopy, Immunoelectron; D008928:Mitochondria / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D017411:Ribonucleoproteins, Small Nuclear; C488681:Tdrd1 protein, mouse; C090864:Ddx4 protein, mouse; D053487:DEAD-box RNA Helicases