Primary sex determination in birds depends on DMRT1 dosage, but gonadal sex does not determine adult secondary sex characteristics.
Primary sex determination in birds depends on DMRT1 dosage, but gonadal sex does not determine adult secondary sex characteristics.
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DOI：
10.1073/pnas.2020909118
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发表时间：
2021-03-09
影响因子：
11.1
通讯作者：
Clinton M
中科院分区：
文献类型：
--
作者：
Ioannidis J;Taylor G;Zhao D;Liu L;Idoko-Akoh A;Gong D;Lovell-Badge R;Guioli S;McGrew MJ;Clinton M
在这里，我们表明DMRT1剂量是鸟类性别决定的关键因素，对睾丸发育至关重要。此外，我们提供了额外的证据表明，与哺乳动物相比，鸟类已经获得了细胞自主性别认同（CASI），性激素环境对鸟类第二性征没有显著影响。这一发现突出了哺乳动物和非哺乳脊椎动物之间的进化鸿沟。在哺乳动物中，性染色体决定性腺形成的类型，性激素在很大程度上决定第二性表型。在鸟类中，性表型直接由不同组织中单个细胞的性染色体含量决定。我们的发现有助于我们进一步理解性别决定系统的进化和性别认同的本质。在鸟类中，雄性为同质性（ZZ），雌性为异质性（ZW）。主要的性别决定被认为取决于性染色体基因的剂量机制，最可能的性别决定因素是Z染色体基因双性和单克隆抗体-3相关转录因子1 （DMRT1）。为了澄清这一问题，我们使用基于crispr - cas9的单等位基因靶向方法和无菌替代宿主来产生DMRT1基因靶向突变的鸟类。由此得到的染色体雄性（ZZ）鸡具有单一的DMRT1功能拷贝，而不是睾丸，这表明鸟类性别决定机制是基于DMRT1剂量的。这些ZZ卵巢表达了典型的女性标记，并显示出卵泡发育的明显证据。然而，这些用卵巢代替睾丸的ZZ成年鸟在外观上与野生型成年雄性无法区分，这支持了鸟类细胞自主性别认同（CASI）的概念。在实验中，在对照ZW胚胎中，雌激素合成被阻断，由此产生的性腺发育为睾丸。相反，如果雌激素合成在缺乏DMRT1的ZW胚胎中被阻断，性腺总是采用卵巢的命运。我们的分析表明，DMRT1是鸟类中关键的性别决定开关，它对睾丸发育至关重要，但雌性激素的产生也是鸡主要性别决定的关键因素，这种产生与DMRT1的表达有关。
Here, we show that DMRT1 dosage is the key sex determination factor in birds and is essential for testis development. Furthermore, we provide additional evidence that birds, in contrast to mammals, have acquired cell-autonomous sex identity (CASI) and that the sex hormone environment does not significantly influence avian secondary sexual characteristics. This finding highlights an evolutionary divide between mammals and nonmammalian vertebrates. In mammals, the sex chromosomes determine the type of gonad formed, and sex hormones largely define the secondary sexual phenotype. In birds, the sexual phenotype is directly determined by the sex chromosome content of individual cells in different tissues. Our findings help advance our understanding of the evolution of sex determination systems and the nature of sex identity. In birds, males are the homogametic sex (ZZ) and females the heterogametic sex (ZW). Primary sex determination is thought to depend on a sex chromosome gene dosage mechanism, and the most likely sex determinant is the Z chromosome gene Doublesex and Mab-3–Related Transcription factor 1 (DMRT1). To clarify this issue, we used a CRISPR-Cas9–based monoallelic targeting approach and sterile surrogate hosts to generate birds with targeted mutations in the DMRT1 gene. The resulting chromosomally male (ZZ) chicken with a single functional copy of DMRT1 developed 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 estrogen synthesis was blocked in control ZW embryos, the resulting gonads developed as testes. In contrast, if estrogen synthesis was blocked in ZW embryos that lacked DMRT1, 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 estrogen is also a key factor in primary sex determination in chickens, and that this production is linked to DMRT1 expression.
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影响因子：
4.6
作者：
Idoko-Akoh A;Taylor L;Sang HM;McGrew MJ
通讯作者：
McGrew MJ
影响因子：
3.5
作者：
Pannetier, Maelle;Fabre, Stephane;Pailhoux, Eric
通讯作者：
Pailhoux, Eric
影响因子：
16.6
作者：
Ballantyne M;Woodcock M;Doddamani D;Hu T;Taylor L;Hawken RJ;McGrew MJ
通讯作者：
McGrew MJ
影响因子：
4.6
作者：
Guioli, Silvana;Lovell-Badge, Robin
通讯作者：
Lovell-Badge, Robin
影响因子：
2.7
作者：
Ayers, K. L.;Cutting, A. D.;Smith, C. A.
通讯作者：
Smith, C. A.