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Article
Nature 436, 207-213 (14 July 2005) | doi:10.1038/nature03813; Received 17 March 2005; Accepted 10 May 2005; Published online 5 June 2005
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Blimp1 is a critical determinant of the germ cell lineage in mice
Yasuhide Ohinata1,7, Bernhard Payer2,7, Dónal O'Carroll3,7, Katia Ancelin2, Yukiko Ono1, Mitsue Sano1, Sheila C. Barton2, Tetyana Obukhanych4, Michel Nussenzweig4, Alexander Tarakhovsky3, Mitinori Saitou1,5,6 & M. Azim Surani2
- Laboratory for Mammalian Germ Cell Biology, Center for Developmental Biology, RIKEN Kobe Institute, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 Japan
- Wellcome Trust/Cancer Research UK Gurdon Institute of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK
- The Laboratory for Lymphocyte Signaling and
- The Laboratory of Molecular Immunology, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
- Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan
- Laboratory of Molecular Cell Biology and Development, Graduate School of Biostudies, Kyoto University, Oiwake-cho, Kitashirakawa, Sakyo-ku, Kyoto 606-8502, Japan
- *These authors contributed equally to this work
Correspondence to: Mitinori Saitou1,5,6M. Azim Surani2 Correspondence and requests for materials should be addressed to M.A.S. (Email: as10021@mole.bio.cam.ac.uk) or M.S. (Email: saitou@cdb.riken.jp).
Abstract
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.
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