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In germ cells of mouse embryonic ovaries, the decision to enter meiosis precedes premeiotic DNA replication


The transition from mitosis to meiosis is a defining juncture in the life cycle of sexually reproducing organisms. In yeast, the decision to enter meiosis is made before the single round of DNA replication that precedes the two meiotic divisions1. We present genetic evidence of an analogous decision point in the germ line of a multicellular organism. The mouse Stra8 gene is expressed in germ cells of embryonic ovaries, where meiosis is initiated, but not in those of embryonic testes, where meiosis does not begin until after birth2. Here we report that in female embryos lacking Stra8 gene function, the early, mitotic development of germ cells is normal, but these cells then fail to undergo premeiotic DNA replication, meiotic chromosome condensation, cohesion, synapsis and recombination. Combined with previous findings, these genetic data suggest that active differentiation of ovarian germ cells commences at a regulatory point upstream of premeiotic DNA replication.

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Figure 1: Photomicrographs of hematoxylin and eosin–stained ovarian sections from wild-type and Stra8-deficient littermate embryos.
Figure 2: Testing ovarian germ cells for molecular markers of meiotic prophase.
Figure 3: Histograms of cellular DNA content in embryonic ovaries.
Figure 4: Photomicrographs of hematoxylin and eosin–stained sections from wild-type and Stra8-deficient testes at 7 or 8 d after birth.

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We thank R. Jaenisch (Whitehead Institute for Biomedical Research) for v6.5 ES cells; A. Bortvin, T. Hassold and T. Ashley for advice; C. Heyting (Department of Genetics, Agricultural University, Wageningen) for SCP3 and REC8 antisera; T. Noce (Mitsubishi Kagaku Institute of Life Science) for MVH antisera and E. Anderson, G. Baltus, M. Capelson, M. Gill, J. Koubova, J. Lange, Y. Lim, J. Mueller and J. Potash for comments on the manuscript. Microscopy and image capture were conducted in part at the W.M. Keck Foundation Biological Imaging Facility at the Whitehead Institute. A.E.C. is a Novartis Fellow of the Life Sciences Research Foundation. This work was supported by the Howard Hughes Medical Institute.

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Correspondence to David C Page.

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Supplementary information

Supplementary Fig. 1

Targeted disruption of the Stra8 locus. (PDF 781 kb)

Supplementary Fig. 2

Germ cell loss and reduced gonadal size in Stra8-deficient mice. (PDF 876 kb)

Supplementary Fig. 3

Alignment of predicted amino acid sequences of STRA8 homologs identified electronically. (PDF 105 kb)

Supplementary Table 1

Oligonucleotide sequences. (PDF 35 kb)

Supplementary Note (PDF 65 kb)

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Baltus, A., Menke, D., Hu, YC. et al. In germ cells of mouse embryonic ovaries, the decision to enter meiosis precedes premeiotic DNA replication. Nat Genet 38, 1430–1434 (2006).

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