Department of Veterinary Anatomy, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Department of Experimental Animal Model for Human Disease, Center for Experimental Animals, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
Biol Reprod. 2018 Sep 1;99(3):578-589. doi: 10.1093/biolre/ioy079.
In mouse conceptus, two yolk-sac membranes, the parietal endoderm (PE) and visceral endoderm (VE), are involved in protecting and nourishing early-somite-stage embryos prior to the establishment of placental circulation. Both PE and VE membranes are tightly anchored to the marginal edge of the developing placental disk, in which the extraembryonic endoderm (marginal zone endoderm: ME) shows the typical flat epithelial morphology intermediate between those of PE and VE in vivo. However, the molecular characteristics and functions of the ME in mouse placentation remain unclear. Here, we show that SOX17, not SOX7, is continuously expressed in the ME cells, whereas both SOX17 and SOX7 are coexpressed in PE cells, by at least 10.5 days postconception. The Sox17-null conceptus, but not the Sox7-null one, showed the ectopic appearance of squamous VE-like epithelial cells in the presumptive ME region, together with reduced cell density and aberrant morphology of PE cells. Such aberrant ME formation in the Sox17-null extraembryonic endoderm was not rescued by the chimeric embryo replaced with the wild-type gut endoderm by the injection of wild-type ES cells into the Sox17-null blastocyst, suggesting the cell autonomous defects in the extraembryonic endoderm of Sox17-null concepti. These findings provide direct evidence of the crucial roles of SOX17 in proper formation and maintenance of the ME region, highlighting a novel entry point to understand the in vivo VE-to-PE transition in the marginal edge of developing placenta.
在小鼠胚胎中，两个卵黄囊膜，即壁内胚层（PE）和内脏内胚层（VE），在胎盘循环建立之前，参与保护和滋养早期体节期胚胎。PE 和 VE 膜都紧密地固定在胎盘盘的边缘，其中胚胎外内胚层（边缘区内胚层：ME）表现出与体内的 PE 和 VE 之间的典型扁平上皮形态中间态。然而，ME 在小鼠胎盘形成中的分子特征和功能仍不清楚。在这里，我们表明 SOX17 而不是 SOX7 在 ME 细胞中持续表达，而 SOX17 和 SOX7 都在 PE 细胞中共同表达，至少在受孕后 10.5 天。 Sox17 缺失的胚胎，而不是 Sox7 缺失的胚胎，在假定的 ME 区域出现了鳞状 VE 样上皮细胞的异位出现，同时 PE 细胞的细胞密度降低和形态异常。这种 Sox17 缺失的胚胎外内胚层中的异常 ME 形成，通过将野生型 ES 细胞注射到 Sox17 缺失的胚泡中替换为野生型肠道内胚层的嵌合胚胎，不能得到挽救，这表明 Sox17 缺失的胚胎外内胚层中的细胞自主缺陷。这些发现为 SOX17 在 ME 区域的正确形成和维持中的关键作用提供了直接证据，突出了一个新的切入点来理解发育中胎盘边缘的体内 VE-PE 转换。
