Primary sex determination in chickens depends on DMRT1 dosage, but gonadal sex does not determine secondary sexual characteristics in adult birds

Primary sex determination in chickens depends on DMRT1 dosage, but gonadal sex does not determine secondary sexual characteristics in adult birds
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鸡的第一性别决定取决于 DMRT1 剂量,但性腺性别并不决定成年鸟类的第二性征

DOI:
10.1101/2020.09.18.303040
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发表时间:
2020
期刊:
--
影响因子:
--
通讯作者:
Ioannidis J
Ioannidis J
中科院分区:
--
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--
作者:
Ioannidis J

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在鸟类中,雄性是同配性别(ZZ),雌性是异配性别(ZW),初级性别决定被认为取决于性染色体基因剂量机制。以前的研究表明,最可能的性别决定因素是Z染色体基因DMRT 1(Doublemex和Mab-3相关转录因子1)。为了澄清这个问题,我们使用了基于CRISPR-Cas9的单等位基因靶向方法和无菌替代宿主来产生DMRT 1基因中具有靶向突变的鸟类。由此产生的染色体雄性(ZZ)鸡与一个单一的功能拷贝的DMRT 1开发卵巢的地方睾丸,表明鸟类性别决定机制是基于DMRT 1剂量。这些ZZ卵巢表达典型的女性标记物,并显示出卵泡发育的明确证据。然而,这些ZZ成年鸟类的卵巢代替睾丸是无法区分的外观野生型成年男性,支持细胞自主性的性别身份(CASI)的概念在鸟类。在实验中,雌激素的合成被阻止在控制ZW胚胎,由此产生的性腺发育为睾丸。相反,如果雌激素合成在缺乏DMRT 1的ZW胚胎中被阻断,性腺总是会接受卵巢的命运。我们的分析表明,DMRT 1是鸟类性别决定的关键开关,它对睾丸发育至关重要,但雌激素的产生也是鸡初级性别决定的关键因素,而且这种产生与DMRT 1的表达有关。
In birds, males are the homogametic sex (ZZ) and females the heterogametic sex (ZW), and primary sex determination is thought to depend on a sex chromosome gene dosage mechanism. Previous studies have suggested that the most likely sex-determinant is the Z chromosome geneDMRT1(Doublesex and Mab-3 Related Transcription factor 1). To clarify this issue, we used a CRISPR-Cas9 based mono-allelic targeting approach and sterile surrogate hosts to generate birds with targeted mutations in theDMRT1gene. The resulting chromosomally male (ZZ) chicken with a single functional copy ofDMRT1developed ovaries in place of testes, demonstrating the avian sex determining mechanism is based on DMRT1 dosage. These ZZ ovaries expressed typical female markers and showed clear evidence of follicular development. However, these ZZ adult birds with an ovary in place of testes were indistinguishable in appearance to wild type adult males, supporting the concept of cell-autonomous sex identity (CASI) in birds. In experiments where oestrogen synthesis was blocked in control ZW embryos, the resulting gonads developed as testes. In contrast, if oestrogen synthesis was blocked in ZW embryos that lackedDMRT1, the gonads invariably adopted an ovarian fate. Our analysis shows that DMRT1 is the key sex determination switch in birds and that it is essential for testis development, but that production of oestrogen is also a key factor in primary sex determination in chickens, and that this production is linked to DMRT1 expression.
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