Chen Yao, Ma Li, Hogarth Cathryn, Wei Gang, Griswold Michael D, Tong Ming-Han
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China Shanghai Key Laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
CAS-MPG Partner Institute for Computational Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Development. 2016 May 1;143(9):1502-11. doi: 10.1242/dev.135939. Epub 2016 Mar 10.
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 α (RARα) 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.
维甲酸（RA）信号对于精原细胞分化至关重要，而精原细胞分化是精子发生的关键步骤。我们通过将维甲酸受体α（RARα）的显性负性突变体特异性靶向转基因小鼠的生殖细胞以破坏内源性受体的活性，来探索精原细胞分化的潜在机制。在此我们表明：（1）生殖细胞中类视黄醇信号的抑制完全阻断了精原细胞分化，这与维生素A缺乏（VAD）小鼠的情况相同；（2）类视黄醇信号受损导致的精原细胞分化阻滞是由于未分化精原细胞进入S期受阻所致；（3）类视黄醇信号通过控制其直接靶基因的表达来调节精原细胞分化，这些靶基因包括依赖复制的核心组蛋白基因。综上所述，我们的结果表明，类视黄醇信号在体内对精原细胞分化的作用是直接通过精原细胞自身实现的，并首次提供了证据表明这是由依赖复制的核心组蛋白基因表达的调控介导的。
