Dmrt1 is necessary for male sexual development in zebrafish.
Dmrt1 is necessary for male sexual development in zebrafish.
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DMRT1对于斑马鱼的男性性发展是必需的。
DOI：
10.1016/j.ydbio.2016.12.008
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发表时间：
2017-02-01
影响因子：
2.7
通讯作者：
Siegfried KR
中科院分区：
文献类型：
--
作者：
Webster KA;Schach U;Ordaz A;Steinfeld JS;Draper BW;Siegfried KR
dmrt 1基因是后生动物性别决定和/或性腺性别分化的关键调控因子。这是不寻常的，因为性别决定基因通常不是很保守。斑马鱼性别决定的机制仍然是难以捉摸的，由于缺乏性染色体和复杂的多基因性决定驯化品系。为了研究dmrt 1在斑马鱼性别决定和性腺发育中的作用，我们分离了破坏该基因的突变。我们发现大多数dmrt 1突变鱼发育为可生育的雌性，这表明在突变动物中完全发生了雄性到雌性的性别逆转，否则这些突变动物会发育为雄性。一小部分突变动物变成雄性，但不育并显示睾丸发育不全。因此，斑马鱼dmrt 1基因在雄性性别决定和睾丸发育中起作用。突变体雄性在性腺性别分化开始时性腺发育异常，表现为卵母细胞凋亡减少，随后出现两性性腺发育，睾丸形态发生和精子发生失败。相比之下，女性卵巢发育正常。我们发现，Dmrt 1是必要的amh（抗苗勒管激素）和foxl 2（叉头框L2）基因，这被认为是重要的男性或女性的性发育分别正常的转录调控。有趣的是，我们确定了一个dmrt 1突变等位基因，与连锁分离扭曲基因座产生一个明显的XY性别决定机制。我们的结论是，dmrt 1是卵巢发育，但在斑马鱼睾丸发育所必需的，和dmrt 1促进雄性发育的转录调节雄性和雌性基因已在其他动物中描述。此外，由dmrt 1功能降低引起的强烈的性别比例偏差指出了性染色体可能进化的潜在机制。
The dmrt1 (doublesex and mab-3 related transcription factor 1) gene is a key regulator of sex determination and/or gonadal sex differentiation across metazoan animals. This is unusual given that sex determination genes are typically not well conserved. The mechanisms by which zebrafish sex is determined have remained elusive due to the lack of sex chromosomes and the complex polygenic nature of sex determination in domesticated strains. To investigate the role of dmrt1 in zebrafish sex determination and gonad development, we isolated mutations disrupting this gene. We found that the majority of dmrt1 mutant fish develop as fertile females suggesting a complete male-to-female sex reversal in mutant animals that would have otherwise developed as males. A small percentage of mutant animals became males, but were sterile and displayed testicular dysgenesis. Therefore zebrafish dmrt1 functions in male sex determination and testis development. Mutant males had aberrant gonadal development at the onset of gonadal sex-differentiation, displaying reduced oocyte apoptosis followed by development of intersex gonads and failed testis morphogenesis and spermatogenesis. By contrast, female ovaries developed normally. We found that Dmrt1 is necessary for normal transcriptional regulation of the amh (anti-Müllerian hormone) and foxl2 (forkhead box L2) genes, which are thought to be important for male or female sexual development respectively. Interestingly, we identified one dmrt1 mutant allele that cooperates with a linked segregation distorter locus to generate an apparent XY sex determination mechanism. We conclude that dmrt1 is dispensable for ovary development but necessary for testis development in zebrafish, and that dmrt1 promotes male development by transcriptionally regulating male and female genes as has been described in other animals. Furthermore, the strong sex-ratio bias caused by dmrt1 reduction-of-function points to potential mechanisms through which sex chromosomes may evolve.
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影响因子：
4
作者：
Liew WC;Orbán L
通讯作者：
Orbán L
影响因子：
2.7
作者：
Dranow, Daniel B.;Tucker, Richard P.;Draper, Bruce W.
通讯作者：
Draper, Bruce W.
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Kobayashi, T;Matsuda, M;Nagahama, Y
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Nagahama, Y
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作者：
Kim, Shinseog;Bardwell, Vivian J.;Zarkower, David
通讯作者：
Zarkower, David
影响因子：
2.7
作者：
Chiang, EFL;Pai, CI;Chung, BC
通讯作者：
Chung, BC