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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Licensing of gametogenesis, dependent on RNA binding protein DAZL, as a gateway to sexual differentiation of fetal germ cells
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Licensing of gametogenesis, dependent on RNA binding protein DAZL, as a gateway to sexual differentiation of fetal germ cells

机译：取决于RNA结合蛋白DAZL的配子发生许可，作为胎儿生殖细胞性别分化的途径

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摘要

Mammalian oocytes and spermatozoa derive from fetal cells shared by the sexes. These primordial germ cells (PGCs) migrate to the developing somatic gonad, giving rise to oocytes or spermatozoa. These opposing sexual fates are determined not by the PGCs' own sex chromosome constitution (XX or XY), but by the sexual identity of the fetal gonad that they enter. We asked whether PGCs undergo a developmental transition that enables them to respond to feminizing or masculinizing cues from fetal ovary or testis. We conducted in vivo genetic studies of DAZL, an RNA-binding protein expressed in both ovarian and testicular germ cells. We found that germ cells in C57BL/6 Daz/-deficient fetuses—whether XX or XY—migrate to the gonad but do not develop either male or female features. Instead, they remain in a sexually undifferentiated state similar to that of migrating PGCs. Thus, germ cells in C57BL/6 Daz/-deficient fetuses do not respond to sexual cues from ovary or testis, whereas the earlier processes of germ cell specification and migration are unaffected. We propose that PGCs of both XX and XY fetuses undergo licensing, an active developmental transition that enables the resultant game-togenesis-competent cells to respond to feminizing or masculinizing cues produced by the fetal ovary or testis and hence to embark on oogenesis or spermatogenesis. In C57BL/6 mice, Dazl is required for licensing. Licensing serves as a gateway from the embryonic processes shared between the sexes—germ cell specification and migration—to the sex-specific pathways of oogenesis and spermatogenesis.
机译：哺乳动物的卵母细胞和精子来自两性共享的胎儿细胞。这些原始生殖细胞（PGC）迁移到发育中的体细胞性腺，从而产生卵母细胞或精子。这些相反的性命运不是由PGC自己的性染色体组成（XX或XY）决定的，而是由它们进入的胎儿性腺的性别特征决定的。我们问PGCs是否经历了发育过渡，使其能够对来自胎儿卵巢或睾丸的女性化或男性化线索做出反应。我们进行了DAZL的体内遗传研究，DAZL是在卵巢和睾丸生殖细胞中表达的一种RNA结合蛋白。我们发现，C57BL / 6 Daz /缺陷型胎儿中的生殖细胞（无论是XX还是XY）都迁移到性腺，但没有发育成男性或女性特征。取而代之的是，它们保持与迁移的PGC相似的性别未分化状态。因此，C57BL / 6 Daz /缺陷型胎儿中的生殖细胞不响应来自卵巢或睾丸的性暗示，而较早的生殖细胞指定和迁移过程不受影响。我们建议XX和XY胎儿的PGC都经过许可，这是一个活跃的发育过渡，能够使产生的具有配子形成能力的细胞对胎儿卵巢或睾丸产生的女性化或男性化的信号作出反应，从而着手进行卵子发生或精子发生。在C57BL / 6小鼠中，Dazl需要许可。从两性之间共享的胚芽过程（生殖细胞规格和迁移）到成卵和生精的性别特定途径，发牌是门户。

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    Mark E. Gill; Yueh-Chiang Hu; Yanfeng Lin; David C. Page;

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    Howard Hughes Medical Institute, Whitehead Institute, and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142;

    Howard Hughes Medical Institute, Whitehead Institute, and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142;

    Howard Hughes Medical Institute, Whitehead Institute, and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142;

    Howard Hughes Medical Institute, Whitehead Institute, and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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