Germ cell fate in mice is induced in pluripotent epiblast cells in response to signals from extraembryonic tissues. The specification of approximately 40 founder primordial germ cells and their segregation from somatic neighbours are important events in early development. We have proposed that a critical event during this specification includes repression of a somatic programme that is adopted by neighbouring cells. Here we show that Blimp1 (also known as Prdm1), a known transcriptional repressor, has a critical role in the foundation of the mouse germ cell lineage, as its disruption causes a block early in the process of primordial germ cell formation. Blimp1-deficient mutant embryos form a tight cluster of about 20 primordial germ cell-like cells, which fail to show the characteristic migration, proliferation and consistent repression of homeobox genes that normally accompany specification of primordial germ cells. Furthermore, our genetic lineage-tracing experiments indicate that the Blimp1-positive cells originating from the proximal posterior epiblast cells are indeed the lineage-restricted primordial germ cell precursors.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1

    Surani, M. A. Reprogramming of genome function through epigenetic inheritance. Nature 414, 122–128 (2001)

  2. 2

    Li, E. Chromatin modification and epigenetic reprogramming in mammalian development. Nature Rev. Genet. 3, 662–673 (2002)

  3. 3

    Gardner, R. L. & Rossant, J. Investigation of the fate of 4–5 day post-coitum mouse inner cell mass cells by blastocyst injection. J. Embryol. Exp. Morphol. 52, 141–152 (1979)

  4. 4

    Lawson, K. A., Meneses, J. J. & Pedersen, R. A. Clonal analysis of epiblast fate during germ layer formation in the mouse embryo. Development 113, 891–911 (1991)

  5. 5

    Lawson, K. A. & Hage, W. J. Clonal analysis of the origin of primordial germ cells in the mouse. Ciba Found. Symp. 182, 68–84 (1994)

  6. 6

    McLaren, A. Primordial germ cells in the mouse. Dev. Biol. 262, 1–15 (2003)

  7. 7

    Lawson, K. A. et al. Bmp4 is required for the generation of primordial germ cells in the mouse embryo. Genes Dev. 13, 424–436 (1999)

  8. 8

    Gardner, R. L., Lyon, M. F., Evans, E. P. & Burtenshaw, M. D. Clonal analysis of X-chromosome inactivation and the origin of the germ line in the mouse embryo. J. Embryol. Exp. Morphol. 88, 349–363 (1985)

  9. 9

    Saitou, M., Barton, S. C. & Surani, M. A. A molecular programme for the specification of germ cell fate in mice. Nature 418, 293–300 (2002)

  10. 10

    Sato, M. et al. Identification of PGC7, a new gene expressed specifically in preimplantation embryos and germ cells. Mech. Dev. 113, 91–94 (2002)

  11. 11

    Surani, M. A. et al. Mechanism of mouse germ cell specification: a genetic program regulating epigenetic reprogramming. Cold Spring Harbor Symp. Quant. Biol. 69, 1–10 (2004)

  12. 12

    Seydoux, G. & Strome, S. Launching the germline in Caenorhabditis elegans: regulation of gene expression in early germ cells. Development 126, 3275–3283 (1999)

  13. 13

    Blackwell, T. K. Germ cells: finding programs of mass repression. Curr. Biol. 14, R229–R230 (2004)

  14. 14

    Santos, A. C. & Lehmann, R. Germ cell specification and migration in Drosophila and beyond. Curr. Biol. 14, R578–R589 (2004)

  15. 15

    Turner, C. A. Jr, Mack, D. H. & Davis, M. M. Blimp-1, a novel zinc finger-containing protein that can drive the maturation of B lymphocytes into immunoglobulin-secreting cells. Cell 77, 297–306 (1994)

  16. 16

    Shapiro-Shelef, M. et al. Blimp-1 is required for the formation of immunoglobulin secreting plasma cells and pre-plasma memory B cells. Immunity 19, 607–620 (2003)

  17. 17

    Shaffer, A. L. et al. Blimp-1 orchestrates plasma cell differentiation by extinguishing the mature B cell gene expression program. Immunity 17, 51–62 (2002)

  18. 18

    Chang, D. H., Cattoretti, G. & Calame, K. L. The dynamic expression pattern of B lymphocyte induced maturation protein-1 (Blimp-1) during mouse embryonic development. Mech. Dev. 117, 305–309 (2002)

  19. 19

    Lange, U. C., Saitou, M., Western, P. S., Barton, S. C. & Surani, M. A. The Fragilis interferon-inducible gene family of transmembrane proteins is associated with germ cell specification in mice. BMC Dev. Biol. 3, doi:10.1186/1471-213X-3-1 (2003)

  20. 20

    Perea-Gomez, A. et al. Initiation of gastrulation in the mouse embryo is preceded by an apparent shift in the orientation of the anterior-posterior axis. Curr. Biol. 14, 197–207 (2004)

  21. 21

    Mesnard, D., Filipe, M., Belo, J. A. & Zernicka-Goetz, M. The anterior-posterior axis emerges respecting the morphology of the mouse embryo that changes and aligns with the uterus before gastrulation. Curr. Biol. 14, 184–196 (2004)

  22. 22

    Rossant, J. & Tam, P. P. Emerging asymmetry and embryonic patterning in early mouse development. Dev. Cell 7, 155–164 (2004)

  23. 23

    Ginsburg, M., Snow, M. H. & McLaren, A. Primordial germ cells in the mouse embryo during gastrulation. Development 110, 521–528 (1990)

  24. 24

    de Sousa Lopes, S. M. et al. BMP signalling mediated by ALK2 in the visceral endoderm is necessary for the generation of primordial germ cells in the mouse embryo. Genes Dev. 18, 1838–1849 (2004)

  25. 25

    Payer, B. et al. stella is a maternal effect gene required for normal early development in mice. Curr. Biol. 13, 2110–2117 (2003)

  26. 26

    Mao, X., Fujiwara, Y., Chapdelaine, A., Yang, H. & Orkin, S. H. Activation of EGFP expression by Cre-mediated excision in a new ROSA26 reporter mouse strain. Blood 97, 324–326 (2001)

  27. 27

    Lomeli, H., Ramos-Mejia, V., Gertsenstein, M., Lobe, C. G. & Nagy, A. Targeted insertion of Cre recombinase into the TNAP gene: excision in primordial germ cells. Genesis 26, 116–117 (2000)

  28. 28

    Vincent, S. D. et al. The zinc finger transcriptional repressor Blimp1/Prdm1 is dispensable for early axis formation but is required for specification of primordial germ cells in the mouse. Development 132, 1315–1325 (2005)

  29. 29

    Nagy, A. Manipulating the Mouse Embryo: a Laboratory Manual (Cold Spring Harbor Lab. Press, Cold Spring Harbor, 2003)

  30. 30

    Forlani, S., Lawson, K. A. & Deschamps, J. Acquisition of Hox codes during gastrulation and axial elongation in the mouse embryo. Development 130, 3807–3819 (2003)

  31. 31

    Saito, H., Kubota, M., Roberts, R. W., Chi, Q. & Matsunami, H. RTP family members induce functional expression of mammalian odorant receptors. Cell 119, 679–691 (2004)

  32. 32

    Wilkinson, D. G. & Nieto, M. A. Detection of messenger RNA by in situ hybridization to tissue sections and whole mounts. Methods Enzymol. 225, 361–373 (1993)

  33. 33

    Seki, Y. et al. Extensive and orderly reprogramming of genome-wide chromatin modifications associated with specification and early development of germ cells in mice. Dev. Biol. 278, 440–458 (2005)

  34. 34

    Cox, W. G. & Singer, V. L. A high-resolution, fluorescence-based method for localization of endogenous alkaline phosphatase activity. J. Histochem. Cytochem. 47, 1443–1456 (1999)

Download references


We thank S. Chuva de Sousa Lopes, K. Nakao, H. Miyachi and R. Nakayama for technical help, and T. Nakano for anti-stella/PGC7 antibody. B.P. was supported by a Wellcome Trust PhD studentship. M.A.S. is funded by the BBSRC, the Wellcome Trust and the EU Epigenome Programme. M.S. is supported by the Ministry of Education, Culture, Sports, Science and Technology, and a PRESTO grant by the JST. D.O'C. acknowledges the support of the Irvington Institute for Immunological Research and is their National Genetics Foundation Fellow. Thanks to K. Lawson and A. McLaren for discussions and critical comments.

Author information

Author notes

  1. Yasuhide Ohinata, Bernhard Payer and Dónal O'Carroll: *These authors contributed equally to this work


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

    • Yasuhide Ohinata
    • , Yukiko Ono
    • , Mitsue Sano
    •  & Mitinori Saitou
  2. Wellcome Trust/Cancer Research UK Gurdon Institute of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, CB2 1QN, Cambridge, UK

    • Bernhard Payer
    • , Katia Ancelin
    • , Sheila C. Barton
    •  & M. Azim Surani
  3. The Laboratory for Lymphocyte Signaling

    • Dónal O'Carroll
    •  & Alexander Tarakhovsky
  4. The Laboratory of Molecular Immunology, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, 10021, New York, USA

    • Tetyana Obukhanych
    •  & Michel Nussenzweig
  5. Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, 332-0012, Saitama, Japan

    • Mitinori Saitou
  6. Laboratory of Molecular Cell Biology and Development, Graduate School of Biostudies, Kyoto University, Oiwake-cho, Kitashirakawa, Sakyo-ku, 606-8502, Kyoto, Japan

    • Mitinori Saitou


  1. Search for Yasuhide Ohinata in:

  2. Search for Bernhard Payer in:

  3. Search for Dónal O'Carroll in:

  4. Search for Katia Ancelin in:

  5. Search for Yukiko Ono in:

  6. Search for Mitsue Sano in:

  7. Search for Sheila C. Barton in:

  8. Search for Tetyana Obukhanych in:

  9. Search for Michel Nussenzweig in:

  10. Search for Alexander Tarakhovsky in:

  11. Search for Mitinori Saitou in:

  12. Search for M. Azim Surani in:

Competing interests

Reprints and permissions information is available at The authors declare no competing financial interests.

Corresponding authors

Correspondence to Mitinori Saitou or M. Azim Surani.

Supplementary information

  1. Supplementary Methods

    This file contains additional information on the methods used in this study, including the antibodies used and the generation of transgenic and knockout mouse strains described in the paper. (DOC 33 kb)

  2. Supplementary Figure Legends

    Legends to accompany the below Supplementary Figures. (DOC 35 kb)

  3. Supplementary Figure S1

    Single cell analysis of germ cell marker expression during PGC-specification and fragilis in situ hybridisations. (JPG 64 kb)

  4. Supplementary Figure S2

    Description of the Blimp-1-mEGFP transgene and its expression during PGC-specification. (JPG 57 kb)

  5. Supplementary Figure S3

    Co-staining of TNAP and Blimp-1-mEGFP in MB stage embryos. (JPG 64 kb)

  6. Supplementary Figure S4

    Creation of Blimp-1 mutant allele. The figure contains a description of the targeting strategy and verification of successful targeting by Southern blotting and RT–PCR. (JPG 67 kb)

  7. Supplementary Figure S5

    Comparison of E9.5 embryos generated from Blimp-1 control (loxP/loxP) and null (-/-) ES-cells injected into tetraploid blastocysts. TNAP-stainings revealled a lack or gross reduction of PGCs in the mutants. (JPG 52 kb)

About this article

Publication history




Issue Date


Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.