A W-linked DM-domain gene, DM-W, participates in primary ovary development in Xenopus laevis
A W-linked DM-domain gene, DM-W, participates in primary ovary development in Xenopus laevis
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DOI：
10.1073/pnas.0712244105
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发表时间：
2008-02-19
影响因子：
11.1
通讯作者：
Ito, Michihiko
中科院分区：
文献类型：
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作者：
Yoshimoto, Shin;Okada, Ema;Ito, Michihiko
在XX/XY性别决定系统中，大多数哺乳动物的Y连锁SRY基因和硬骨鱼青鳉的DMY/Dmrt1bY基因已被定性为触发睾丸形成的性别决定基因。然而，脊椎动物（包括爪蛙非洲爪蟾）中 ZZ/ZW 型系统的分子机制尚不清楚。在这里，我们分离了非洲爪蟾雌性基因组特异性 DM 结构域基因 DM-W，并获得了该物种中 W 染色体的分子证据。 DM-W 的 DNA 结合结构域与 DMRT1 的 DNA 结合结构域显示出惊人的高同一性 (89%)，但它与 DMRT1 的反式激活结构域没有显着的序列相似性。在非哺乳动物脊椎动物中，DMRT1 表达与睾丸形成有关。我们发现 DMRT1 或 DM-W 分别仅在 ZZ 和 ZW 或 ZW 蝌蚪的原始性腺中表达。尽管 DMRT1 在性别决定后持续表达，但 DM-W 在性别决定过程中短暂表达。有趣的是，在性别决定早期，ZW 蝌蚪的原始性腺中 DM-W mRNA 比 DMRT1 mRNA 更丰富。为了评估 DM-W 的作用，我们生产了携带 DM-W 表达载体的转基因蝌蚪，该表达载体由约 3 kb 的 DM-W 5'侧翼序列或巨细胞病毒启动子驱动。重要的是，ZZ 转基因蝌蚪的一些发育中的性腺显示出具有两种驱动因素的卵巢腔和初级卵母细胞，这表明 DM-W 对于初级卵巢的形成至关重要。总而言之，这些结果表明 DM-W 可能是非洲爪蟾的性别（卵巢）决定基因。
In the XX/XY sex-determining system, the Y-linked SRY genes of most mammals and the DMY/Dmrt1bY genes of the teleost fish medaka have been characterized as sex-determining genes that trigger formation of the testis. However, the molecular mechanism of the ZZ/ZW-type system in vertebrates, including the clawed frog Xenopus laevis, is unknown. Here, we isolated an X. laevis female genome-specific DM-domain gene, DM-W, and obtained molecular evidence of a W-chromosome in this species. The DNA-binding domain of DM-W showed a strikingly high identity (89%) with that of DMRT1, but it had no significant sequence similarity with the transactivation domain of DMRT1. In nonmammalian vertebrates, DMRT1 expression is connected to testis formation. We found DMRT1 or DM-W to be expressed exclusively in the primordial gonads of both ZZ and ZW or ZW tadpoles, respectively. Although DMRT1 showed continued expression after sex determination, DM-W was expressed transiently during sex determination. Interestingly, DM-W mRNA was more abundant than DMRT1 mRNA in the primordial gonads of ZW tadpoles early in sex determination. To assess the role of DM-W, we produced transgenic tadpoles carrying a DM-W expression vector driven by approximate to 3 kb of the 5 '-flanking sequence of DM-W or by the cytomegalovirus promoter. Importantly, some developing gonads of ZZ transgenic tadpoles showed ovarian cavities and primary oocytes with both drivers, suggesting that DM-W is crucial for primary ovary formation. Taken together, these results suggest that DM-W is a likely sex (ovary)-determining gene in X. laevis.