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

外胚层和滋养层谱系中经典Wnt通路活性的差异调节机制

• 批准号: 530277456
• 负责人: Dr. Ivan Bedzhov
• 金额: --
• 依托单位: Forschungsgruppe Embryonic Self-Organization
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/530277456?language=en
• 关键词: Differential; regulatory; mechanisms; canonical; Wnt

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.

发育过程依赖于胚胎和胚外谱系之间紧密调控的信号串扰，协调胚胎的分化和形态发生。在概念中建立的信号中心以自动和旁分泌的方式提供模式线索，指导建立身体轴的细胞命运转变。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体外指导多能细胞命运的分化方案中实施。与此同时，人们对“保护”早期谱系免受信号信号干扰以抵消过早分化的细胞机制知之甚少。在本项目提案中，我们将重点关注典型的Wnt信号通路，这是胚胎着床后早期阶段模式的关键信号通路之一。我们的初步数据表明，与邻近的滋养细胞相比，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，并了解其在滋养细胞发育中的作用。