The Generation of Positional Identity in Mesendoderm; Mechanism(s) of Lineage Specification in Vertebrate Development

中内胚层位置同一性的产生；

• 批准号: G0701429/1
• 负责人: Josh Brickman
• 金额: $ 204.25万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0701429%2F1
• 关键词: Generation; Positional; Identity; Mesendoderm; Mechanism

During early embryonic development, the cells of the future gut move along the midline of the embryo signalling to the nervous system. To understand the molecular instructions driving the differentiation of these cells it is necessary to isolate them from the complex and changing environments in the embryo. Being able to break down this in vivo process of lineage specification is also essential for the generation of gut associated cell types and organs from human ES cells. In this proposal, we utilise genetically modified mouse ES cells that report on differentiation towards the embryonic gut in real time. We have used this system to generate monolayer conditions for ES cell differentiation toward embryonic gut. Our ability to differentiate these cells attached to plastic means that we can easily change media components as well as following differentiation visually. This proposal exploits this system alongside embryonic models to tease apart the stages of differentiation. It contains a program of work that is both focused on identifying new determinants and understanding how these determinants drive differentiation. This proposal will provide basic mechanistic insight into developmental biology and define conditions for the efficient differentiation of ES cells towards organs like the liver and pancreas.

在早期胚胎发育过程中，未来肠道的细胞沿着胚胎的中线向神经系统发出信号。为了理解驱动这些细胞分化的分子指令，有必要将它们从胚胎中复杂和不断变化的环境中分离出来。能够打破这种谱系特化的体内过程对于从人ES细胞产生肠道相关细胞类型和器官也是必不可少的。在这个建议中，我们利用转基因小鼠ES细胞，报告分化向胚胎肠道在真实的时间。我们已经用这个系统来产生单层条件ES细胞分化胚胎肠道。我们能够区分这些附着在塑料上的细胞，这意味着我们可以很容易地改变培养基成分，并在视觉上进行分化。这个提议利用这个系统和胚胎模型来梳理分化的各个阶段。它包含一个工作计划，既侧重于确定新的决定因素，又了解这些决定因素如何推动差异化。该提案将为发育生物学提供基本的机制见解，并定义ES细胞向肝脏和胰腺等器官有效分化的条件。