The avian Z-linked gene DMRT1 is required for male sex determination in the chicken
The avian Z-linked gene DMRT1 is required for male sex determination in the chicken
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DOI：
10.1038/nature08298
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发表时间：
2009-09-10
期刊：
影响因子：
64.8
通讯作者：
Sinclair, Andrew H.
中科院分区：
文献类型：
--
作者：
Smith, Craig A.;Roeszler, Kelly N.;Sinclair, Andrew H.
与哺乳动物一样，鸟类的性别也是基于染色体，但性染色体不同，鸟类性别决定的机制一直是个谜(1-3)。在鸡和所有其他鸟类中，同配性别是雄性（ZZ），异配性别是雌性（ZW）。对于鸟类性别决定的机制提出了两种假设。 W（女性）染色体可能携带显性卵巢决定簇 (4-6)。或者，Z 连锁基因的剂量可能介导性别决定，雄性发育需要两个剂量 (ZZ)(7,8)。剂量假设下的一个强有力的候选鸟类性别决定因素是保守的 Z 连锁基因 DMRT1（双性和 mab-3 相关转录因子 1）(9-11)。在这里，我们使用 RNA 干扰 (RNAi) 来敲低早期鸡胚胎中的 DMRT1。卵中 DMRT1 蛋白表达的减少会导致遗传男性 (ZZ) 胚胎中胚胎性腺的女性化。受影响的男性表现出部分性逆转，其特征是性腺女性化。女性化的左侧性腺显示出类似女性的组织学、紊乱的睾丸索和睾丸标志物 SOX9 的下降。卵巢标记物芳香酶被异位激活。女性化的右性腺显示出更多变化的 DMRT1 损失和异位芳香酶激活，表明左右性腺对 DMRT1 的敏感性不同。生殖细胞在女性化的男性性腺中也显示出女性的分布模式。这些结果表明 DMRT1 是鸡睾丸测定所必需的。我们的数据支持鸟类性别决定的 Z 剂量假说。
Sex in birds is chromosomally based, as in mammals, but the sex chromosomes are different and the mechanism of avian sex determination has been a long-standing mystery(1-3). In the chicken and all other birds, the homogametic sex is male (ZZ) and the heterogametic sex is female (ZW). Two hypotheses have been proposed for the mechanism of avian sex determination. The W ( female) chromosome may carry a dominant-acting ovary determinant(4-6). Alternatively, the dosage of a Z-linked gene may mediate sex determination, two doses being required for male development (ZZ)(7,8). A strong candidate avian sex-determinant under the dosage hypothesis is the conserved Z-linked gene, DMRT1 (doublesex and mab-3-related transcription factor 1)(9-11). Here we used RNA interference (RNAi) to knock down DMRT1 in early chicken embryos. Reduction of DMRT1 protein expression in ovo leads to feminization of the embryonic gonads in genetically male (ZZ) embryos. Affected males show partial sex reversal, characterized by feminization of the gonads. The feminized left gonad shows female-like histology, disorganized testis cords and a decline in the testicular marker, SOX9. The ovarian marker, aromatase, is ectopically activated. The feminized right gonad shows a more variable loss of DMRT1 and ectopic aromatase activation, suggesting differential sensitivity to DMRT1 between left and right gonads. Germ cells also show a female pattern of distribution in the feminized male gonads. These results indicate that DMRT1 is required for testis determination in the chicken. Our data support the Z dosage hypothesis for avian sex determination.