Regionalised signalling within the extraembryonic ectoderm regulates anterior visceral endoderm positioning in the mouse embryo

Regionalised signalling within the extraembryonic ectoderm regulates anterior visceral endoderm positioning in the mouse embryo
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DOI:
10.1016/j.mod.2006.01.004
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发表时间:
2006-04-01
影响因子:
2.6
通讯作者:
Zernicka-Goetz, Magdalena
Zernicka-Goetz, Magdalena
中科院分区:
生物学4区
文献类型:
--
作者:
Richardson, Lucy;Torres-Padilla, Maria-Elena;Zernicka-Goetz, Magdalena

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哺乳动物胚胎中前后轴的发育受胚胎和胚外组织之间相互作用的控制。这是公认的,这些胚外组织之一,前内脏内胚层(AVE),可以抑制后细胞的命运和信号从其他,胚外外胚层(ExE),是必需的后图案。在这里,我们表明,信号从前瞻性的后ExE抑制AVE基因的表达,并影响AVE细胞的分布。在发育5.5天(E5.5)时,对预期的后部而非前部胚外区域进行手术消融,扰乱了AVE细胞的特征性远端至前部分布,并导致AVE结构域的急剧扩张。延时成像研究表明,这种增加是由于AVE标记物的异位表达,这导致AVE的对称定位。在E5.75时,在远端至前部迁移已经开始后,对该相同ExE区域进行手术消融不会影响AVE的定位,表明该效应发生在短时间窗内。相反,将预期的后部而不是前部的胚外区域移植到分离的E5.5胚胎外植体上会大大减少AVE结构域。此外,移植实验表明,信号调节AVE基因表达起源于后ExE,而不是其周围的VE。总之,我们的研究结果表明,从未来的后ExE在一个时间窗口内发出的信号都限制了AVE域,并促进其特定的定位。这首次表明,ExE在原肠胚形成开始前一天已经区域化,以便正确设置小鼠胚胎AP轴的方向。我们提出了一个互惠的功能后ExE和AVE在建立这两个组织的拮抗活性之间的平衡,AP图案必不可少的。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
The development of the anterior-posterior (AP) axis in the mammalian embryo is controlled by interactions between embryonic and extraembryonic tissues. It is well established that one of these extraembryonic tissues, the anterior visceral endoderm (AVE), can repress posterior cell fate and that signalling from the other, the extraembryonic ectoderm (ExE), is required for posterior patterning. Here, we show that signals from the prospective posterior ExE repress AVE gene expression and affect the distribution of the AVE cells. Surgical ablation of the prospective posterior, but not the anterior, extraembryonic region at 5.5 days of development (E5.5) perturbs the characteristic distal-to-anterior distribution of AVE cells and leads to a dramatic expansion of the AVE domain. Time-lapse imaging studies show that this increase is due to the ectopic expression of an AVE marker, which results in a symmetrical positioning of the AVE. Surgical ablation of this same ExE region after the distal-to-anterior migration has already commenced, at E5.75, does not affect the localisation of the AVE, indicating that this effect takes place within a short time window. Conversely, transplanting the prospective posterior, but not the anterior, extraembryonic region onto isolated E5.5 embryonic explants drastically reduces the AVE domain. Further, transplantation experiments demonstrate that the signalling regulating AVE gene expression originates from the posterior ExE, rather than its surrounding VE. Together, our results show that signals emanating from the future posterior ExE within a temporal window both restrict the AVE domain and promote its specific positioning. This indicates for the first time that the ExE is already regionalised a day before the onset of gastrulation in order to correctly set the orientation of the AP axis of the mouse embryo. We propose a reciprocal function of the posterior ExE and the AVE in establishing a balance between the antagonistic activities of these two tissues, essential for AP patterning. (c) 2006 Elsevier Ireland Ltd. All rights reserved.