[jessyhalm]

July 12

Dr Andrew Johnson spoke at the UK National Stem Cell Network annual conference. He and his team from the University of Nottingham have been using a Mexican aquatic salamander called an axolotl to study the evolution and genetics of stem cells - research that supports the development of regenerative medicine to treat the consequences of disease and injury using stem cell therapies. This team has found that there are extraordinary similarities in the development of axolotls and mammals that provide unique opportunities to study the properties of embryonic stem cells and germ cells. These findings are underpinned by a novel theory of evolution that unifies the diversity of mechanisms in animal developmental into a single conceptual framework.

Dr Johnson said "We've produced evidence that pluripotency - the ability of an embryonic stem cell to become absolutely any kind of cell - is actually very ancient in evolutionary terms. Even though received wisdom is that it evolved with mammals, our research suggests that it was there all along, just not in many of the species that people use in the lab. In fact, pluripotent cells probably exist in the embryos of the simple animals from which amphibians evolved.

"Axolotls, unlike many of the frogs, fish, flies and worms that are used in the lab, have pluripotent cells in their embryos that are the equivalent to those found in embryos from mammals, in that they can produce germ cells, in addition to somatic cells, a property known as ground-state pluripotency. And from a practical perspective, axolotl embryos will provide a very useful tool for understanding how to manipulate embryonic stem cells for modern regenerative medicine."

Axolotls are salamanders that retained primitive characteristics of the first amphibians, the animals descended from fish that moved onto land about 385 million years ago. These early amphibians were the ancestors of every land dwelling vertebrate, including humans. This places axolotls in a perfect position to understand how vertebrates evolved on land.

Dr Johnson continued "We've found that the genetic mechanisms controlling the development of salamander embryos were not changed as amphibian embryos evolved into those of reptiles and then, later, mammals. This explains why newts (salamanders) look so much like lizards (reptiles), and since mammals evolved directly from reptiles it makes sense that the genetic mechanisms controlling embryo development remain largely unchanged from axolotls to humans. Axolotl embryos are therefore far more similar to those of humans than the more commonly studied embryos of frogs and fish that most development researchers use.

"We recently found out that pluripotency in axolotls and mammals depends on a gene called Nanog, which frogs do not have. Therefore we think that the Nanog gene was lost from the frog genome after frogs and salamanders evolved separately from their common amphibian ancestor. This is contrary to a long-held opinion that ground-state pluripotency evolved with mammals and suggests that pluripotency could actually be one of the most ancient features of embryos. But since evolution depends on generating advantageous changes, and pluripotency seems to be a good thing - we had to ask ourselves why would frogs have lost the Nanog gene, and with it pluripotency?"