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

doi:10.1073/pnas.0601878103

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

*Department of Development and Differentiation, Institute for Frontier Medical Sciences, and
^§Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan;
^¶Department of Biological Science, Faculty of Science, Kumamoto University, Kumamoto 860-8555, Japan; and
**Mitsubishi Kagaku Institute of Life Sciences, Tokyo 194-8511, Japan

Edited by Kathryn V. Anderson, Sloan–Kettering Institute, New York, NY, and approved August 31, 2006 (received for review March 8, 2006)

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.

Footnotes

^†To whom correspondence should be addressed. E-mail: schuma{at}frontier.kyoto-u.ac.jp
Author contributions: S.C. and N.N. designed research; S.C., M. Hosokawa, K.K., S.K., and M.F. performed research; S.C., M. Hosokawa, K.K., M. Hiyoshi, K.T., and T.N. contributed new reagents/analytic tools; S.C., M. Hosokawa, and K.K. analyzed data; and S.C. wrote the paper.
↵ ^‡Present address: Department of Molecular Psychiatry, Tokyo Institute of Psychiatry, Tokyo 156-8585, Japan.
↵ ^‖Present address: Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, Kumamoto 860-0811, Japan.
The authors declare no conflict of interest.
This article is a PNAS direct submission.
Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. AB183526–AB183529).