The axolotl, originally from Mexico, is often used in research as a model organism. Image credit: Fronx (CC BY 2.0)
Salamanders are a group of amphibians that are well-known for their ability to regenerate lost limbs and other body parts. At the turn of the twentieth century, researchers used salamander embryos as models to understand the basic concepts of how limbs develop in other four-limbed animals, including amphibians, mammals and birds, which are collectively known as “tetrapods”. However, the salamander’s amazing powers of regeneration made it difficult to carry out certain experiments, so researchers switched to using the embryos of other tetrapods – namely chickens and mice – instead.
Studies in chickens, later confirmed in mice and frogs, established that there are two major signaling centers that control how the limbs of tetrapod embryos form and grow: a small group of cells known as the “zone of polarizing activity” within a structure called the “limb bud mesenchyme”; and an overlying, thin ridge of cells called the “apical ectodermal ridge”. Both of these centers release potent signaling molecules that act on cells in the limbs. The cells in the zone of polarizing activity produce a molecule often called Sonic hedgehog, or Shh for short. The apical ectodermal ridge produces another group of signals commonly known as fibroblast growth factors, or simply Fgfs.
Several older studies reported that salamander embryos do not have an apical ectodermal ridge suggesting that these amphibian’s limbs may form differently to other tetrapods. Yet, contemporary models in developmental biology treated salamander limbs like those of chicks and mice. To address this apparent discrepancy, Purushothaman et al. studied how the forelimbs develop in a salamander known as the axolotl.
The experiments showed that, along with lacking an apical ectodermal ridge, axolotls did not produce fibroblast growth factors normally found in this tissue. Instead, these factors were only found in the limb bud mesenchyme. Purushothaman et al. also found that fibroblast growth factors played a different role in axolotls than previously reported in chick, frog and mouse embryos. On the other hand, the pattern and function of Shh activity in the axolotl limb bud was similar to that previously observed in chicks and mice.
These findings show that not all limbs develop in the same way and open up questions for evolutionary biologists regarding the evolution of limbs. Future studies that examine limb development in other animals that regenerate tissues, such as other amphibians and lungfish, will help answer these questions.
