The induction of PGCs from pluripotent cells in axolotl embryos

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During normal animal development the cells that are egg and sperm come from cells called primordial germ cells, or PGCs. Little is known about how PGCs form in humans, but this is very important, because it can help with fertility problems, and with understanding the origins of ovarian and testicular tumors. Also, PGCs come from precursor cells that are pluripotent, which means they can become any other cell in the body. In this way PGCs are very similar to embryonic stem cells, or ES cells. Understanding how ES cells form, and retain their capacity for becoming other cells, is a major goal of modern biomedical science. A fundamental approach to modern developmental biology is to study how cells behave in the embryos of less advanced animals, then transfer knowledge from these studies to understand how similar processes are controlled in mammals, and ultimately humans. This approach is useful because the embryos of lower animals are usually much larger and easy to manipulate, and so experiments are less expensive and easier to perform. Also, this approach minimizes the distress that more advanced animals might encounter. Many scientists use embryos from frogs or from fish, but the species usually used form PGCs through a mechanism that is not relevant to humans. We developed axolotl embryos as model experimental system because it produces PGCs in a manner very similar to humans. As proof of this we have previously cloned genes from this species that are known to be required in human pluripotent cells. Using embryos from axolotls has allowed us to understand how pluripotent cells are produced in normal embryos, and how they are governed during development. In this work we prove for the first time that PGCs can be induced in vast numbers, in a highly enriched form, using very simple methods that we developed. Here we are working to further validate and refine our methods, and to understand the actual genes and mechanisms that are involved in PGCs formation. This system will make PGCs useful as novel tools to understand how pluripotency is controlled. Also, this work will be very important in aiding our understanding of how stem cells develop in embryos, and how germ cells are made distinct from other types of cells in the body.