March 25, 2010
Strange BiologyRemaining Salamander Limb Cells Remember Identity After Amputation
Certain types of amphibians including axolotls and newts are able to regenerate lost limbs. These animals have been widely studied by scientists interested in learning the mechanics behind limb regeneration. Following amputation of a limb, a cap of skin cells grows over the leftover stump, forming a blastema. Cells that will reform the lost limb come from the blastema.
Some types of amphibians, such as this axolotl, are able to regenerate lost limbs. (Photo credit: Photoshot Holdings Ltd/Alamy)
Previous studies indicated that cells in the blastema lost their identity and turned into pluripotent stem cells, meaning they could develop into whatever kind of cell was needed, such as skin, muscle, bone, or cartilage. However, research by scientists based at Germany’s Dresden University of Technology indicates that this is not the case. Instead, the cells left behind following limb amputation “remember” what they are and multiply to form the same type of tissue in the new limb.
In their study, the researchers genetically modified an axolotl to express the green fluorescent protein (GFP) in all of its body cells. The scientists then took samples of GFP-producing skin, muscle, nerve, and cartilage cells from the genetically-modified axolotl and transplanted the tissues into different axolotl embryos. By tagging these cell types with GFP, the scientists could follow the fate of the tagged cells during limb regeneration.
Following maturation, the scientists amputated one of the axolotl’s limbs and observed the limb’s regeneration. If the cells lost their identity and became pluripotent, the scientists would expect to see a salt-and-pepper effect in the new limb, meaning the GFP-producing cells would be spread throughout the new limb, and not only in one area, such as just in new nerve tissue.
According to the researchers, this was not the case. Instead, the scientists discovered that only the tissues engineered to produce GFP in the old limb glowed in the new limb. For example, remaining muscle cells multiplied to make muscle cells in the new limb, nerve cells multiplied to make new nerve cells, and so on. The researchers also found that skin cells were able to differentiate into either skin or cartilage cells, while other cell types (such as muscle and cartilage) could not differentiate into other types of cells. In addition, cartilage cells had a strong sense of identity compared to other cell types, and “knew” whether they came from an upper limb or lower limb.
The scientists are interested in determining how universal these results are; that is, whether the process occurs in the same way in other animals in which limb regeneration can occur. The results of the scientists’ research were published in the July 2, 2009 edition of the journal Nature. Scientists who contributed to the research include Martin Kragl, Dunja Knapp, Eugen Nacu, Shahryar Khattak, Malcolm Maden, Hans Henning Epperlein, and Elly M. Tanaka.