Differential regulatory mechanisms of canonical Wnt pathway activity in the epiblast and trophoblast lineages

发育过程依赖于胚胎和胚外谱系之间严格调控的信号串扰，协调胚胎的分化和形态发生。在概念中建立的信号中心以一种自动和旁分泌的方式提供图案提示，指导细胞命运转变，从而建立身体轴。在过去的几十年里，已经确定了多种协调胚胎模式的因素，其中许多因素已经在分化方案中实施，这些分化方案指导着体外多能细胞的命运。与此同时，人们对早期谱系的细胞机制知之甚少，这些机制使早期谱系免受信号提示的影响，从而抵消了过早的分化。在这个项目提案中，我们关注的是典型的Wnt信号，它是胚胎植入后早期形成模式的关键信号通路之一。我们的初步数据显示，与邻近的滋养层细胞相比，外胚层对Wnt刺激有强烈的反应。在这里，我们试图破译Wnt活性差异的细胞机制，并了解其在滋养层发育中的作用。

The developmental progression relies on tightly regulated signalling crosstalk between the embryonic and the extraembryonic lineages coordinating the differentiation and morphogenesis of the embryo. Signalling centres established in the conceptus provide patterning cues in an auto- and paracrine manner directing cell fate transitions that set up the body axes. Multiple factors orchestrating embryo patterning have been identified over the last decades and many of them have been implemented in differentiation protocols directing the fate of pluripotent cells in vitro. At the same time, less is known about the cellular mechanisms that “shield” the early lineages from signalling cues in order to counteract premature differentiation. In this project proposal, we focus on the canonical Wnt signalling, which is one of the key signalling pathways that pattern the embryo during the early post-implantation stages. Our preliminary data show that the epiblast robustly responds to Wnt stimulation, in contrast to the neighbouring trophoblast cells. Here we seek to decipher the cellular mechanisms of the differential Wnt activity and understand its role in trophoblast development.