DICER Regulates the Formation and Maintenance of Cell-Cell Junctions in the Mouse Seminiferous Epithelium
DICER Regulates the Formation and Maintenance of Cell-Cell Junctions in the Mouse Seminiferous Epithelium
复制标题
DOI：
10.1095/biolreprod.115.131938
复制
发表时间：
2015-12-01
影响因子：
3.6
通讯作者：
Kotaja, Noora
中科院分区：
文献类型：
--
作者：
Korhonen, Hanna Maria;Yadav, Ram Prakash;Kotaja, Noora
内切核酸酶DICER处理微小RNA和小干扰RNA，对正常精子发生和男性生育力至关重要。我们以前表明，Dicer 1基因在小鼠出生后精原细胞中使用Ngn 3启动子驱动的Cre表达的缺失造成了严重的缺陷，在单倍体精子细胞成熟精子的形态发生，包括细胞极化和核伸长的问题。在这项研究中，我们进一步分析了相同的小鼠模型，并揭示了在分化雄性生殖细胞中缺乏功能性DICER会诱导生精上皮中细胞-细胞连接的解体。我们检测到不连续和不规则的顶端内质网专业化之间的精子细胞和支持细胞。精子细胞与支持细胞的锚定缺陷导致精子细胞过早释放到管腔中。我们的发现也可能有助于解释剩余精子细胞的异常伸长过程，因为这些连接和生殖细胞在上皮中的正确定位对于精子发生的进展至关重要。有趣的是，细胞粘附相关基因通常在Dicer 1敲除生殖细胞中上调。Claudin 5（Cldn 5）是上调最多的基因之一，我们发现Claudin 5在顶端外质特化中的极化定位在Dicer 1敲除精子细胞中丢失。我们的研究结果表明，DICER依赖性途径通过调节细胞粘附相关基因来控制生精上皮细胞间连接的形成和组织。
The endonuclease DICER that processes micro-RNAs and small interfering RNAs is essential for normal spermatogenesis and male fertility. We previously showed that the deletion of Dicer1 gene in postnatal spermatogonia in mice using Ngn3 promoter-driven Cre expression caused severe defects in the morphogenesis of haploid spermatid to mature spermatozoon, including problems in cell polarization and nuclear elongation. In this study, we further analyzed the same mouse model and revealed that absence of functional DICER in differentiating male germ cells induces disorganization of the cell-cell junctions in the seminiferous epithelium. We detected discontinuous and irregular apical ectoplasmic specializations between elongating spermatids and Sertoli cells. The defective anchoring of spermatids to Sertoli cells caused a premature release of spermatids into the lumen. Our findings may help also explain the abnormal elongation process of remaining spermatids because these junctions and the correct positioning of germ cells in the epithelium are critically important for the progression of spermiogenesis. Interestingly, cell adhesion-related genes were generally upregulated in Dicer1 knockout germ cells. Claudin 5 (Cldn5) was among the most upregulated genes and we show that the polarized localization of CLAUDIN5 in the apical ectoplasmic specializations was lost in Dicer1 knockout spermatids. Our results suggest that DICER-dependent pathways control the formation and organization of cell-cell junctions in the seminiferous epithelium via the regulation of cell adhesion-related genes.