The mammalian doublesex homolog DMRT1 is a transcriptional gatekeeper that controls the mitosis versus meiosis decision in male germ cells.
The mammalian doublesex homolog DMRT1 is a transcriptional gatekeeper that controls the mitosis versus meiosis decision in male germ cells.
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DOI：
10.1016/j.devcel.2010.09.010
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发表时间：
2010-10-19
影响因子：
11.8
通讯作者：
Zarkower, David
中科院分区：
文献类型：
--
作者：
Matson, Clinton K.;Murphy, Mark W.;Griswold, Michael D.;Yoshida, Shosei;Bardwell, Vivian J.;Zarkower, David
从有丝分裂到减数分裂的转变是生殖细胞发育的独特特征。在哺乳动物中，减数分裂起始需要视黄酸（RA），视黄酸激活减数分裂诱导剂，包括Stra 8，但在雄性生殖细胞（精原细胞）中如何控制减数分裂的转换仍然知之甚少。在这里，我们研究的作用，在成年人精子发生中的Doublemex-related转录因子DMRT 1使用条件基因打靶在小鼠。Dmrt 1基因缺失导致精原细胞提前退出精原细胞程序并进入减数分裂。因此，dmrt 1决定了雄性生殖细胞是否进行有丝分裂和精原细胞分化或减数分裂。精原细胞中Dmrt 1的缺失也破坏了支持细胞中的周期性基因表达。DMRT 1在精原细胞中发挥作用，限制RA的反应性，直接抑制Stra 8的转录，并激活精原细胞分化因子Sohlh 1的转录，从而阻止减数分裂并促进精原细胞发育。通过协调精原细胞发育和有丝分裂扩增与减数分裂，DMRT 1允许大量的，连续的精子生产。
The switch from mitosis to meiosis is a unique feature of germ cell development. In mammals, meiotic initiation requires retinoic acid (RA), which activates meiotic inducers including Stra8, but how the switch to meiosis is controlled in male germ cells (spermatogonia) remains poorly understood. Here we examine the role of the Doublesex-related transcription factor DMRT1 in adult spermatogenesis using conditional gene targeting in the mouse. Loss of Dmrt1 causes spermatogonia to precociously exit the spermatogonial program and enter meiosis. Dmrt1 therefore determines whether male germ cells undergo mitosis and spermatogonial differentiation or meiosis. Loss of Dmrt1 in spermatogonia also disrupts cyclical gene expression in Sertoli cells. DMRT1 acts in spermatogonia to restrict RA responsiveness, directly repress Stra8 transcription, and activate transcription of the spermatogonial differentiation factor Sohlh1, thereby preventing meiosis and promoting spermatogonial development. By coordinating spermatogonial development and mitotic amplification with meiosis, DMRT1 allows abundant, continuous production of sperm.
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影响因子：
11.8
作者：
Guris, DL;Duester, G;Imamoto, A
通讯作者：
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作者：
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Zarkower, David
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作者：
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