Department of Biology, Waseda University, 2-2 Wakamatsu-cho, Shinjuku, Tokyo 162-8480, Japan.
Genes Cells. 2009 Dec;14(12):1359-67. doi: 10.1111/j.1365-2443.2009.01353.x. Epub 2009 Nov 16.
Left-right (LR) patterning is an essential part of the animal body plan. Primary cilia are known to play a pivotal role in this process. In humans, genetic disorders of ciliogenesis cause serious congenital diseases. A comprehensive mechanism that regulates ciliogenesis has not been proposed so far. Here, we show that EED, a core member of the Polycomb group (PcG) genes and a presumed player in many epigenetic processes, is required for ciliogenesis and subsequent LR patterning in the medaka fish, Oryzias latipes. Moderate knockdown of oleed, a medaka homolog of EED, preferentially caused situs inversus. In the affected embryo, the cilia in Kupffer's vesicle showed various defects in their structure, position and motility. Furthermore, we demonstrated that oleed maintains the expression of Noto, which, in mice, regulates ciliogenesis and LR patterning. This study provides the first evidence for the involvement of epigenetic plasticity in LR patterning through ciliogenesis.
左右（LR）模式是动物体计划的重要组成部分。已知初级纤毛在这个过程中起着关键作用。在人类中，纤毛发生的遗传障碍会导致严重的先天性疾病。到目前为止，还没有提出一个全面的调节纤毛发生的机制。在这里，我们表明，EED，多梳组（PcG）基因的核心成员之一，以及许多表观遗传过程中的假定参与者，是秀丽隐杆线虫，Oryzias latipes 中纤毛发生和随后的 LR 模式所必需的。中度敲低 oleed，EED 的秀丽隐杆线虫同源物，优先导致 situs inversus。在受影响的胚胎中，Kupffer 囊泡中的纤毛在结构、位置和运动方面表现出各种缺陷。此外，我们证明 oleed 维持 Noto 的表达，在小鼠中，Noto 调节纤毛发生和 LR 模式。这项研究首次提供了通过纤毛发生参与 LR 模式的表观遗传可塑性的证据。
