Sex Reversal and Comparative Data Undermine the W Chromosome and Support Z-linked DMRT1 as the Regulator of Gonadal Sex Differentiation in Birds
Sex Reversal and Comparative Data Undermine the W Chromosome and Support Z-linked DMRT1 as the Regulator of Gonadal Sex Differentiation in Birds
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DOI：
10.1210/en.2017-00316
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发表时间：
2017-09-01
期刊：
影响因子：
4.8
通讯作者：
Smith, Craig A.
中科院分区：
文献类型：
--
作者：
Hirst, Claire E.;Major, Andrew T.;Smith, Craig A.
调控鸟类性腺性别分化的确切遗传机制尚未完全阐明。最可能的情况涉及剂量机制，即Z-连锁DMRT 1基因触发睾丸发育。然而，女性特异性W染色体可能携带卵巢决定因子的可能性仍然存在。在这项研究中，我们提供的证据表明，通用基因调节性腺性别分化的鸟类是Z-连锁DMRT 1，而不是W-连锁（卵巢）的因素。三个候选的W-连锁卵巢决定因子是HINTW，女性表达转录本1（FET 1）和女性相关因子（FAF）。为了测试这些基因与鸡卵巢分化的相关性，我们使用芳香酶抑制剂法倔唑（FAD）在实验诱导的雌性到雄性性逆转后检测了它们的表达。在胚胎发生的第3天，FAD的管理诱导了雌性性腺和雄性化芳香化酶活性的显着损失。然而，HINTW，FAF和FET 1的表达水平在实验雄性化后没有改变。此外，比较分析表明，FAF和FET 1在斑胸草雀性腺中未检测到表达。此外，针对预测的HINTW蛋白质产生的抗体未能内源性地检测到它。这些数据不支持这些基因或W性染色体在鸟类卵巢发育中的普遍作用。我们发现，DMRT 1（但不是最近确定的Z-连锁HEMGN基因）是男性上调在胚胎斑胸草雀和鸸鹋性腺，在鸡。由于鸡、斑胸草雀和鸸鹋是鸟类的主要进化分支，我们认为Z-连锁DMRT 1而不是W性染色体调节鸟类的性腺性别分化。
The exact genetic mechanism regulating avian gonadal sex differentiation has not been completely resolved. The most likely scenario involves a dosage mechanism, whereby the Z-linked DMRT1 gene triggers testis development. However, the possibility still exists that the female-specific W chromosome may harbor an ovarian determining factor. In this study, we provide evidence that the universal gene regulating gonadal sex differentiation in birds is Z-linked DMRT1 and not a W-linked (ovarian) factor. Three candidate W-linked ovarian determinants are HINTW, female-expressed transcript 1 (FET1), and female-associated factor (FAF). To test the association of these genes with ovarian differentiation in the chicken, we examined their expression following experimentally induced female-to-male sex reversal using the aromatase inhibitor fadrozole (FAD). Administration of FAD on day 3 of embryogenesis induced a significant loss of aromatase enzyme activity in female gonads and masculinization. However, expression levels of HINTW, FAF, and FET1 were unaltered after experimental masculinization. Furthermore, comparative analysis showed that FAF and FET1 expression could not be detected in zebra finch gonads. Additionally, an antibody raised against the predicted HINTW protein failed to detect it endogenously. These data do not support a universal role for these genes or for the W sex chromosome in ovarian development in birds. We found that DMRT1 (but not the recently identified Z-linked HEMGN gene) is male upregulated in embryonic zebra finch and emu gonads, as in the chicken. As chicken, zebra finch, and emu exemplify the major evolutionary clades of birds, we propose that Z-linked DMRT1, and not the W sex chromosome, regulates gonadal sex differentiation in birds.