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A molecular programme for the specification of germ cell fate in mice

Nature volume 418, pages 293–300 (2002)Cite this article

Abstract

Germ cell fate in mice is induced in proximal epiblast cells by the extra-embryonic ectoderm, and is not acquired through the inheritance of any preformed germ plasm. To determine precisely how germ cells are specified, we performed a genetic screen between single nascent germ cells and their somatic neighbours that share common ancestry. Here we show that fragilis, an interferon-inducible transmembrane protein, marks the onset of germ cell competence, and we propose that through homotypic association, it demarcates germ cells from somatic neighbours. Using single-cell gene expression profiles, we also show that only those cells with the highest expression of fragilis subsequently express stella, a gene that we detected exclusively in lineage-restricted germ cells. The stella positive nascent germ cells exhibit repression of homeobox genes, which may explain their escape from a somatic cell fate and the retention of pluripotency.

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Figure 1: Organization of nascent PGCs.
Figure 2: fragilis (a–e) and stella (f–h) expression in the germline-competent and lineage-restricted germ cells during gastrulation.
Figure 3: Localization of fragilis and stella by immunofluorescence confocal microscopy a, Partially dissociated cells from an early bud stage (E7.5) embryonic fragment bearing PGCs doubly stained with a rabbit anti-fragilis polyclonal antibody and propidium iodide (PI).
Figure 4: Molecular characterization of Bmp4 negative single PGCs and neighbouring somatic cells.
Figure 5: Gene expression profiles of Bmp4 negative single PGCs and neighbouring somatic cells.
Figure 6: fragilis expression is inducible by extra-embryonic tissues and is dose dependent on Bmp4.
Figure 7: Gene expression profiles of distal epiblast cells induced by extra-embryonic ectoderm in vitro.
Figure 8: Organization of the niche for PGC specification.

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Acknowledgements

We thank K. Lawson for providing unpublished information and for discussions, and A. McLaren for critical comments during the course of this study. We also thank Y. Tanabe and T. Yamamoto for helpful information concerning the construction of single cell cDNAs. We are grateful to the Wellcome Trust for support through a Wellcome Travelling Fellowship to M.S. and for a Programme Grant to M.A.S.

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  1. Wellcome Trust/Cancer Research UK Institute of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, CB2 1QR, Cambridge, UK

    Mitinori Saitou, Sheila C. Barton & M. Azim Surani

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  1. Mitinori Saitou
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Correspondence to M. Azim Surani.

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Saitou, M., Barton, S. & Surani, M. A molecular programme for the specification of germ cell fate in mice. Nature 418, 293–300 (2002). https://doi.org/10.1038/nature00927

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