Establishing the GRN for the Germ Line Mesoderm of Axolotl Embryos

建立蝾螈胚胎种系中胚层的GRN

• 批准号: G1100025/1
• 负责人: Andrew Johnson
• 金额: $ 58.42万
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G1100025%2F1
• 关键词: Establishing; GRN; Germ; Line; Mesoderm

Sperm cells and egg cells are produced from cells that form early in embryonic development called primordial germ cells, or PGCs. Understanding how PGCs are established during development of the embryos is important because it will lead to fertility treatments, and also because poorly formed sperm and eggs can give rise to embryos with developmental problems. Little is known about how PGCs are formed in humans because it is impossible to work with human embryos. In addition, mouse embryos, which share many characteristics with humans, also develop in a uterus, and are very small, and therefore are difficult to access. We developed an experimental system using embryos from a salamander called an axolotl. Unlike embryos from mammals, axolotl embryos are very large and they develop in water, and therefore hundreds of embryos are easy to acquire at a time. Also, because they do not develop in a uterus, the embryos can be acquired from natural fertilization, without harm to the adults. What makes axolotls unique for this study, however, is the fact that axolotl embryos produce PGCs using the same genes that humans do, and this makes the genes involved in making PGCs easy to identify. We developed a way to produce thousands of PGCs at a time using very specific conditions. Because the cells are so abundant we will be able to do DNA sequencing to identify the genes and do experiments to understand how the genes interact with each other. The results from our experiments will allow us to develop new ways to produce sperm cells and eggs from embryonic stem cells, which is a major goal of modern medicine.

精子细胞和卵细胞是由胚胎发育早期形成的细胞产生的，这些细胞被称为原始生殖细胞（PGC）。了解 PGC 在胚胎发育过程中如何建立非常重要，因为这将导致生育治疗，而且还因为形成不良的精子和卵子可能会产生有发育问题的胚胎。人们对 PGCs 在人体中是如何形成的知之甚少，因为它不可能在人类胚胎中发挥作用。此外，与人类有许多共同特征的小鼠胚胎也在子宫中发育，而且非常小，因此很难获得。我们利用蝾螈的胚胎开发了一个实验系统。与哺乳动物的胚胎不同，蝾螈胚胎非常大，并且在水中发育，因此一次很容易获得数百个胚胎。此外，由于胚胎不在子宫中发育，因此可以通过自然受精获得胚胎，而不会对成年人造成伤害。然而，蝾螈在这项研究中的独特之处在于，蝾螈胚胎使用与人类相同的基因产生 PGC，这使得参与产生 PGC 的基因很容易识别。我们开发了一种使用非常特定的条件一次生产数千个 PGC 的方法。由于细胞数量如此丰富，我们将能够进行 DNA 测序来识别基因，并进行实验来了解基因如何相互作用。我们的实验结果将使我们能够开发出从胚胎干细胞产生精子细胞和卵子的新方法，这是现代医学的一个主要目标。