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Critical function of Prdm14 for the establishment of the germ cell lineage in mice

Nature Genetics volume 40, pages 1016–1022 (2008)Cite this article

Abstract

Specification of germ cell fate is fundamental in development and heredity. Recent evidence indicates that in mice, specification of primordial germ cells (PGCs), the common source of both oocytes and spermatozoa, occurs through the integration of three key events: repression of the somatic program1, reacquisition of potential pluripotency2,3 and ensuing genome-wide epigenetic reprogramming4,5. Here we provide genetic evidence that Prdm14, a PR domain–containing transcriptional regulator with exclusive expression in the germ cell lineage and pluripotent cell lines, is critical in two of these events, the reacquisition of potential pluripotency and successful epigenetic reprogramming. In Prdm14 mutants, the failure of these two events manifests even in the presence of Prdm1 (also known as Blimp1), a key transcriptional regulator for PGC specification6,7. Our combined evidence demonstrates that Prdm14 defines a previously unknown genetic pathway, initiating independently from Prdm1, for ensuring the launching of the mammalian germ cell lineage.

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Figure 1: Expression of Prdm14 in germ cell development.
Figure 2: Function of Prdm14 in germ cell development.
Figure 3: Prdm14 is critical in regaining a genetic pathway for potential pluripotency in the germ cell lineage.
Figure 4: Prdm14-deficient cells show stalled epigenetic reprogramming and fail to form EG cell–like colonies in culture.
Figure 5: Genetic interactions of Prdm14 with Prdm1, Bmp4 and Smad1.
Figure 6: A conceptual model for the specification of germ cell fate in mice.

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Acknowledgements

We thank A. Miyawaki (RIKEN) for the Venus plasmid, S. Yamanaka (Kyoto University) for the antibody to Sox2, Y. Shinkai and M. Tachibana (Kyoto University) for the antibody to GLP, A. Tarakhovsky (Rockefeller University) and D. O'Carroll (EMBL) for the Prdm1-knockout mice, B. Hogan (Duke University) and K. Lawson (University of Edinburgh) for the Bmp4-knockout mice and K. Hayashi (University of Cambridge) for the Smad1-knockout mice. We thank D. Sipp for his help in manuscript preparation. Y.S., K.K. and Y.O. are fellows in the Special Postdoctoral Researchers Program of RIKEN. This study was supported in part by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and by a PRESTO project grant from the Japan Science and Technology Agency.

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Author notes

  1. Masashi Yamaji, Yoshiyuki Seki and Kazuki Kurimoto: These authors contributed equally to this work.

Authors and Affiliations

  1. Laboratory for Mammalian Germ Cell Biology, Center for Developmental Biology, RIKEN Kobe Institute, 2-2-3 Minatojima-Minamimachi, Chuo-ku, 650-0047, Kobe, Japan

    Masashi Yamaji, Yoshiyuki Seki, Kazuki Kurimoto, Yukihiro Yabuta, Mihoko Yuasa, Mayo Shigeta, Kaori Yamanaka, Yasuhide Ohinata & Mitinori Saitou

  2. Laboratory of Molecular Cell Biology and Development, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, 606-8501, Kyoto, Japan

    Masashi Yamaji & Mitinori Saitou

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  1. Masashi Yamaji
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Contributions

M. Yamaji, Y.S. and M. Saitou designed this study. M. Yamaji, Y.S. and K.K. performed phenotype assessment. M. Saitou, Y.Y. and Y.O. helped phenotype assessment. M. Yuasa, M. Shigeta and K.Y. helped generation and propagation of the mouse strains. M. Saitou wrote this paper.

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Correspondence to Mitinori Saitou.

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Supplementary Table 1, Supplementary Figures 1–7 (PDF 1159 kb)

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Yamaji, M., Seki, Y., Kurimoto, K. et al. Critical function of Prdm14 for the establishment of the germ cell lineage in mice. Nat Genet 40, 1016–1022 (2008). https://doi.org/10.1038/ng.186

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