Retinoid signaling controls spermatogonial differentiation by regulating expression of replication-dependent core histone genes
Retinoid signaling controls spermatogonial differentiation by regulating expression of replication-dependent core histone genes
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类维生素A信号通过调节复制依赖性核心组蛋白基因的表达来控制精原细胞分化
DOI：
10.1242/dev.135939
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发表时间：
2016-05-01
期刊：
影响因子：
4.6
通讯作者：
Tong, Ming-Han
中科院分区：
文献类型：
--
作者：
Chen, Yao;Ma, Li;Tong, Ming-Han
精原细胞分化是精子发生的关键步骤，视黄酸（RA）信号通路在精原细胞分化中起着重要作用。我们通过将视黄酸受体α（RAR α）的显性负突变体特异性表达到转基因小鼠的生殖细胞来破坏内源性受体的活性，从而探索精原细胞分化的潜在机制。在这里，我们表明：（1）维生素A缺乏（VAD）小鼠精原细胞的分化完全被抑制，（2）未分化的精原细胞进入S期受阻，从而导致维生素A信号传导障碍;维甲酸信号通过调控其直接靶基因的表达来调控精原细胞分化，包括复制依赖的核心组蛋白基因。两者合计，我们的研究结果表明，在体内的视黄酸信号对精原细胞分化的作用是直接通过精原细胞本身，并提供了第一个证据表明，这是由复制依赖的核心组蛋白基因的表达调控介导的。
Retinoic acid (RA) signaling is crucial for spermatogonial differentiation, which is a key step for spermatogenesis. We explored the mechanisms underlying spermatogonial differentiation by targeting expression of a dominant-negative mutant of retinoic acid receptor alpha (RAR alpha) specifically to the germ cells of transgenic mice to subvert the activity of endogenous receptors. Here we show that: (1) inhibition of retinoid signaling in germ cells completely blocked spermatogonial differentiation identical to vitamin A-deficient (VAD) mice; (2) the blockage of spermatogonial differentiation by impaired retinoid signaling resulted from an arrest of entry of the undifferentiated spermatogonia into S phase; and (3) retinoid signaling regulated spermatogonial differentiation through controlling expression of its direct target genes, including replication-dependent core histone genes. Taken together, our results demonstrate that the action of retinoid signaling on spermatogonial differentiation in vivo is direct through the spermatogonia itself, and provide the first evidence that this is mediated by regulation of expression of replication-dependent core histone genes.